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  • 2005-2009
  • 2000-2004  (315)
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  • 1
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    On Non-Rank Facets of Stable Set Polytopes of Webs with Clique Number Four (2003)
    Details
    Publication Date: 2014-11-10
    Description: Graphs with circular symmetry, called webs, are relevant w.r.t. describing the stable set polytopes of two larger graph classes, quasi-line graphs and claw-free graphs. Providing a decent linear description of the stable set polytopes of claw-free graphs is a long-standing problem. However, even the problem of finding all facets of stable set polytopes of webs is open. So far, it is only known that stable set polytopes of webs with clique number $\leq 3$ have rank facets only while there are examples with clique number $〉4$ having non-rank facets.
    Keywords: ddc:000
    Language: English
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  • 2
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    Multiscale Analysis for the Bio-Heat Transfer Equation (2003)
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    Publication Date: 2014-02-26
    Description: The bio-heat transfer equation is a macroscopic model for describing the heat transfer in microvascular tissue. In [{\sl Deuflhard, Hochmuth 2002}] the authors applied homogenization techniques to derive the bio-heat transfer equation as asymptotic result of boundary value problems which provide a microscopic description for microvascular tissue. Here those results are generalized to a geometrical setting where the regions of blood are allowed to be connected. Moreover, asymptotic corrector results are derived.
    Keywords: ddc:000
    Language: English
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  • 3
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    Polyhedral Investigations on Stable Multi-Sets (2003)
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    Publication Date: 2014-11-10
    Description: Stable multi-sets are an evident generalization of the well-known stable sets. As integer programs, they constitute a general structure which allows for a wide applicability of the results. Moreover, the study of stable multi-sets provides new insights to well-known properties of stable sets. In this paper, we continue our investigations started in [{\sl Koster and Zymolka 2002}] and present results of three types: on the relation to other combinatorial problems, on the polyhedral structure of the stable multi-set polytope, and on the computational impact of the polyhedral results. First of all, we embed stable multi-sets in a framework of generalized set packing problems and point out several relations. The second part discusses properties of the stable multi-set polytope. We show that the vertices of the linear relaxation are half integer and have a special structure. Moreover, we strengthen the conditions for cycle inequalities to be facet defining, show that the separation problem for these inequalities is polynomial time solvable, and discuss the impact of chords in cycles. The last result allows to interpret cliques as cycles with many chords. The paper is completed with a computational study to the practical importance of the cycle inequalities. The computations show that the performance of state-of-the-art integer programming solvers can be improved significantly by including these inequalities.
    Keywords: ddc:000
    Language: English
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  • 4
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    Formation and structure of quasi-static cloud-layers in brown dwarf atmospheres (2003)
    Details
    Publication Date: 2014-02-26
    Description: In this paper, first solutions of the dust moment equations developed in [{\sl Woitke & Helling 2002}] for the description of dust formation and precipitation in brown dwarf and giant gas planet atmospheres are presented. We consider the special case of a static brown dwarf atmosphere, where dust particles continuously nucleate from the gas phase, grow by the accretion of molecules, settle gravitationally and re-evaporate thermally. Applying a kinetic description of the relevant microphysical and chemical processes for TiO$_2$-grains, the model makes predictions about the large-scale stratification of dust in the atmosphere, the depletion of molecules from the gas phase, the supersaturation of the gas in the atmosphere as well as the mean size and the mass fraction of dust grains as function of depth. Our results suggest that the nucleation occu in the upper atmosphere where the gas is cool, strongly depleted, but nevertheless highly supersaturated ($S\!\gg\!1$). These particles settle gravitationally and populate the warmer layers below, where the in-situ formation (nucleation) is ineffective or even not possible. During their descent, the particles grow up to radii $\approx\!0.3\,\mu{\rm m}\,...\,150\,\mu{\rm m}$, depending gas around the cloud base. The particles finally sink into layers which are sufficiently hot to cause their thermal evaporation. Hence, an effective transport mechanism for condensable elements exi considered solid/liquid material. In the stationary case studied here, this downward directed element transport by precipitating dust grains is balanced by an upward directed flux of condensable elements from the deep interior of the star via convective mixing (no dust without mixing). We find a self-regulation mechanism which leads to an approximate phase equilibrium ($S\!\approx\!1$) around the cloud base. The mass fraction of dust present in the atmosphere results be to approximately given by the mass fraction of condensable elements in the gas being mixed up.
    Keywords: ddc:000
    Language: English
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  • 5
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    Visualization of Time-Dependent Adaptive Mesh Refinement Data (2003)
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    Publication Date: 2020-03-09
    Description: Analysis of phenomena that simultaneously occur on quite different spatial and temporal scales require adaptive, hierarchical schemes to reduce computational and storage demands. For data represented as grid functions, the key are adaptive, hierarchical, time-dependent grids that resolve spatio-temporal details without too much redundancy. Here, so-called AMR grids gain increasing popularity. For visualization and feature identification/tracking, the underlying continuous function has to be faithfully reconstructed by spatial and temporal interpolation. Well designed interpolation methods yield better results and help to reduce the amount of data to be stored. We address the problem of temporal interpolation of AMR grid data, e.g.\ for creation of smooth animations or feature tracking. Intermediate grid hierarchies are generated by merging the cells on all refinement levels that are present in the key frames considered. Utilizing a clustering algorithm a structure of nested grids is induced on the resulting collection of cells. The grid functions are mapped to the intermediate hierarchy, thus allowing application of appropriate interpolation techniques.
    Keywords: ddc:000
    Language: English
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  • 6
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    Tensor Splats (2003)
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    Publication Date: 2020-03-09
    Description: An improved general-purpose technique for the visualization of symmetric positive definite tensor fields of rank two is described. It is based on a splatting technique that is built from tiny transparent glyph primitives which are capable to incorporate the full directional information content of a tensor. The result is an information-rich image that allows to read off the preferred directions in a tensor field at each point of a three-dimensional volume or two-dimensional surface. It is useful for analyzing slices or volumes of a three-dimensional tensor field and can be overlayed with standard volume rendering or color mapping. The application of the rendering technique is demonstrated on general relativistic data and the diffusion tensor field of a human brain.
    Keywords: ddc:000
    Language: English
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  • 7
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    A construction for non-rank facets of stable set polytopes of webs (2003)
    Details
    Publication Date: 2014-11-10
    Description: Graphs with circular symmetry, called webs, are relevant for describing the stable set polytopes of two larger graph classes, quasi-line graphs [{\sl Giles and Trotter 1981, Oriolo 2001}] and claw-free graphs [{\sl Galluccio and Sassano 1997, Giles and Trotter 1981}]. Providing a decent linear description of the stable set polytopes of claw-free graphs is a long-standing problem [{\sl Grötschel, Lov\'asz, and Schrijver 1988}]. However, even the problem of finding all facets of stable set polytopes of webs is open. So far, it is only known that stable set polytopes of webs with clique number $\leq 3$ have rank facets only [{\sl Dahl 1999, Trotter 1975}] while there are examples with clique number $\geq 4$ having non-rank facets [{\sl e.g. Liebling et al. 2003, Oriolo 2001, P\^echer and Wagler 2003}]. In this paper, we provide a construction for non-rank facets of stable set polytopes of webs. We use this construction to prove, for several fixed values of $\omega$ including all odd values at least 5, that there are only finitely many webs with clique number $\omega$ whose stable set polytopes admit rank facets only.
    Keywords: ddc:000
    Language: English
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  • 8
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    Automatic Construction of Boundary Parametrizations for Geometric Multigrid Solvers (2003)
    Details
    Publication Date: 2020-11-13
    Description: We present an algorithm that constructs parametrizations of boundary and interface surfaces automatically. Starting with high-resolution triangulated surfaces describing the computational domains, we iteratively simplify the surfaces yielding a coarse approximation of the boundaries with the same topological type. While simplifying we construct a function that is defined on the coarse surface and whose image is the original surface. This function allows access to the correct shape and surface normals of the original surface as well as to any kind of data defined on it. Such information can be used by geometric multigrid solvers doing adaptive mesh refinement. Our algorithm runs stable on all types of input surfaces, including those that describe domains consisting of several materials. We have used our method with success in different fields and we discuss examples from structural mechanics and biomechanics.
    Keywords: ddc:000
    Language: English
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  • 9
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    Combinatorial Packing Problems (2003)
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    Publication Date: 2020-08-05
    Description: This article investigates a certain class of combinatorial packing problems and some polyhedral relations between such problems and the set packing problem.
    Keywords: ddc:000
    Language: English
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  • 10
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    Small Examples of Non-Constructible Simplicial Balls and Spheres (2003)
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    Publication Date: 2014-02-26
    Description: We construct non-constructible simplicial $d$-spheres with $d+10$ vertices and non-constructible, non-realizable simplicial $d$-balls with $d+9$ vertices for $d\geq 3$.
    Keywords: ddc:000
    Language: English
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  • 11
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    A Lagrangian Approach for Integrated Network Design and Routing in IP Networks (2003)
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    Publication Date: 2014-11-11
    Description: We consider the problem of designing a network that employs a non-bifurcated shortest path routing protocol. The network's nodes and the set of potential links are given together with a set of forecasted end-to-end traffic demands. All relevant hardware components installable at links or nodes are considered. The goal is to simultaneously choose the network's topology, to decide which hardware components to install on which links and nodes, and to find appropriate routing weights such that the overall network cost is minimized. In this paper, we present a mathematical optimization model for this problem and an algorithmic solution approach based on a Lagrangian relaxation. Computational results achieved with this approach for several real-world network planning problems are reported.
    Keywords: ddc:000
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  • 12
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    Comparing Restoration Concepts using Optimal Network Configurations with Integrated Hardware and Routing Decisions (2003)
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    Publication Date: 2014-02-26
    Description: We investigate the impact of link and path restoration on the cost of telecommunication networks. The surprising result is the following: the cost of an optimal network configuration is almost independent of the restoration concept if (i) the installation of network elements (ADMs, DXCs, or routers) and interface cards, (ii) link capacities, and (iii) working and restoration routings are simultaneously optimized. We present a mixed-integer programming model which integrates all these decisions. Using a branch-and-cut algorithm (with column generation to deal with all potential routing paths), we solve structurally different real-world problem instances and show that the cost of optimal solutions is almost independent of the used restoration concept. In addition, we optimize spare capacities for given shortest working paths which are predetermined with respect to different link metrics. In comparison to simultaneous optimization of working and restoration routings, it turns out that this approach does not allow to obtain predictably good results.
    Keywords: ddc:000
    Language: English
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  • 13
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    Average Case Analysis of a Hard Dial-a-Ride Problem (2003)
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    Publication Date: 2020-11-13
    Description: In the dial-a-ride-problem (DARP) objects have to be moved between given sources and destinations in a transportation network by means of a server. The goal is to find a shortest transportation for the server. We study the DARP when the underlying transportation network forms a caterpillar. This special case is strongly NP-hard in the worst case. We prove that in a probabilistic setting there exists a polynomial time algorithm which almost surely finds an optimal solution. Moreover, with high probability the optimality of the solution found can be certified efficiently. We also examine the complexity of the DARP in a semi-random setting and in the unweighted case.
    Keywords: ddc:000
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  • 14
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    Asymptotic Mesh Independence of Newton's Method Revisited (2003)
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    Publication Date: 2019-01-29
    Description: The paper presents a new affine invariant theory on asymptotic mesh independence of Newton's method in nonlinear PDEs. Compared to earlier attempts, the new approach is both much simpler and more natural from the algorithmic point of view. The theory is exemplified at collocation methods for ODE boundary value problems and at finite element methods for elliptic PDE problems.
    Keywords: ddc:000
    Language: English
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  • 15
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    Smoothening Helps: A Probabilistic Analysis of the Multi-Level Feedback Algorithm (2003)
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    Publication Date: 2014-02-26
    Description: In this paper we introduce the notion of smoothed competitive analysis of online algorithms. Smoothed analysis has been proposed by [{\sl Spielman and Teng} STOC 2001] to explain the behaviour of algorithms that work well in practice while performing very poorly from a worst case analysis point of view. We apply this notion to analyze the Multi-Level Feedback (MLF) algorithm to minimize the total flow time on a sequence of jobs released over time when the processing time of a job is only known at time of completion. The initial processing times are integers in the range $[1,2^K]$. We use a partial bit randomization model, where the initial processing times are smoothened by changing the $k$ least significant bits under a quite general class of probability distributions. We show that MLF admits a smoothed competitive ratio of $O(max((2^k/\sigma)^3, (2^k/\sigma)^2 2^K-k))$, where $\sigma$ denotes the standard deviation of the distribution. In particular, we obtain a competitive ratio of $O(2^K-k)$ if $\sigma = \Theta(2^k)$. %The analysis holds for an oblivious as well as for a stronger adaptive %adversary. We also prove an $\Omega(2^{K-k})$ lower bound for any deterministic algorithm that is run on processing times smoothened according to the partial bit randomization model. For various other smoothening models, including the additive symmetric smoothening model used by [{\sl Spielman and Teng}], we give a higher lower bound of $\Omega(2^K)$. A direct consequence of our result is also the first average case analysis of MLF. We show a constant expected ratio of the total flow time of MLF to the optimum under several distributions including the uniform distribution.
    Keywords: ddc:000
    Language: English
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  • 16
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    A sample path relation for the sojourn times in G/G/1-PS systems and its applications (2003)
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    Publication Date: 2014-11-11
    Description: For the general G/G/1 processor sharing (PS) system a sample path result for the sojourn times in a busy period is proved, which yields a relation between the sojourn times under PS and FCFS discipline. In particular, the result provides a formula for the mean sojourn time in G/D/1-PS in terms of the mean sojourn time in the corresponding G/D/1-FCFS, generalizing known results for GI/M/1 and M/GI/1. Extensions of the formula provide the basis for a two-moment approximation of the mean sojourn time in G/GI/1-PS in terms of a related G/D/1-FCFS.
    Keywords: ddc:000
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  • 17
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    Molecular Conformation Dynamics and Computational Drug Design (2003)
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    Publication Date: 2014-02-26
    Description: The paper surveys recent progress in the mathematical modelling and simulation of essential molecular dynamics. Particular emphasis is put on computational drug design wherein time scales of $msec$ up to $min$ play the dominant role. Classical long-term molecular dynamics computations, however, would run into ill-conditioned initial value problems already after time spans of only $psec=10^{-12} sec$. Therefore, in order to obtain results for times of pharmaceutical interest, a combined deterministic-stochastic model is needed. The concept advocated in this paper is the direct identification of metastable conformations together with their life times and their transition patterns. It can be interpreted as a {\em transfer operator} approach corresponding to some underlying hybrid Monte Carlo process, wherein short-term trajectories enter. Once this operator has been discretized, which is a hard problem of its own, a stochastic matrix arises. This matrix is then treated by {\em Perron cluster analysis}, a recently developed cluster analysis method involving the numerical solution of an eigenproblem for a Perron cluster of eigenvalues. In order to avoid the 'curse of dimension', the construction of appropriate boxes for the spatial discretization of the Markov operator requires careful consideration. As a biomolecular example we present a rather recent SARS protease inhibitor.
    Keywords: ddc:000
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  • 18
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    Nonlinear Optimization in Gas Networks (2003)
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    Publication Date: 2021-02-01
    Description: The operative planning problem in natural gas distribution networks is addressed. An optimization model focusing on the governing PDE and other nonlinear aspects is presented together with a suitable discretization for transient optimization in large networks by SQP methods. Computational results for a range of related dynamic test problems demonstrate the viability of the approach.
    Keywords: ddc:000
    Language: English
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  • 19
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    RNA 3D-Modeling (2003)
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    Publication Date: 2014-02-26
    Description: This article presents a new computational approach to the three-dimensional (3D) modeling of ribonucleic acid (RNA) sequences with unknown spatial structure. The main concept is a mapping of the query sequence onto the 3D structures of a suitable template RNA molecule. This technique called \textit{threading} has originally been developed for the modeling of protein 3D structures. The application to RNA systems bridges the information gap between the growing mass of RNA sequence data and the relatively limited number of available 3D structures. The new RNA threading method is demonstrated on a tRNA model system because sufficient representative 3D structures have experimentally been elucidated and deposited in the public databases. Nevertheless, the method is in principle transferable on all other RNA species. Algorithms are developed that decompose these template structures into their secondary structure elements and gather this information in a specific template database. The best template is chosen with public alignment and secondary structure prediction tools which are integrated in the RNA modeling module. The structural information gathered from the template and the best alignment is combined to establish a comprehensive 3D model of the query sequence. A range of complete tRNA structures has successfully been modeled with the RNA threading method. The prototype module visualizes the models and provides convenient access to the proposed 3D structures. Therefore, the method could give new insight into a variety of RNA systems which in the recent years have become increasingly important as potential new pharmaceutical agents.
    Keywords: ddc:000
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  • 20
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    Korean-German Bilateral Symposium on Scientific Computing (2003)
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    Publication Date: 2014-02-26
    Description: Collection of abstracts of the Korean-German Bilateral Symposium on Scientific Computing, Berlin January 15/16, 2004
    Keywords: ddc:000
    Language: English
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  • 21
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    Planung kostenoptimaler Informations- und Kommunikations-Infrastrukturen (2003)
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    Publication Date: 2014-11-11
    Description: Beim Entwurf und Ausbau von Informations- und Kommunikationsnetzwerken m{ü}ssen zahlreiche interdependente Entscheidungen getroffen und gleichzeitig mannigfaltige Bedingungen ber{ü}cksichtigt werden. Die verf{ü}gbaren technischen und organisatorischen Alternativm{ö}glichkeiten sind normalerweise so vielf{ä}ltig und komplex, dass eine manuelle Planung praktisch nicht m{ö}glich ist. In diesem Artikel wird das Potential und die Methodik der mathematischen Optimierung bei der kostenoptimalen Planung von Kommunikationsnetzen vorgestellt. Als Ausgangspunkt wird exemplarisch eine typische praktische Aufgabe, die Struktur- und Konfigurationsplanung mehrstufiger Telekommunikationsnetzwerke, dargestellt. Anschließend werden kurz die wesentlichen Modellierungstechniken und Verfahrensans{ä}tze der mathematischen Optimierung skizziert. Abschließend gehen wir auf die Planung einer ad{ä}quaten Informations- und Kommunikations- Infrastruktur f{ü}r ein dezentrales Energieversorgungsnetz ein.
    Keywords: ddc:000
    Language: German
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  • 22
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    Chromatic Scheduling Polytopes coming from the Bandwidth Allocation Problem in Point-to-Multipoint Radio AccessSystems (2003)
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    Publication Date: 2020-08-05
    Description: Point-to-Multipoint systems are one kind of radio systems supplying wireless access to voice/data communication networks. Such systems have to be run using a certain frequency spectrum, which typically causes capacity problems. Hence it is, on the one hand, necessary to reuse frequencies but, on the other hand, no interference must be caused thereby. This leads to the bandwidth allocation problem, a special case of so-called chromatic scheduling problems. Both problems are NP-hard, and there exist no polynomial time approximation algorithms with a guaranteed quality. One kind of algorithms which turned out to be successful for many other combinatorial optimization problems uses cutting plane methods. In order to apply such methods, knowledge on the associated polytopes is required. The present paper contributes to this issue, exploring basic properties of chromatic scheduling polytopes and several classes of facet-defining inequalities.
    Keywords: ddc:000
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  • 23
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    Optimization Methods for UMTS Radio Network Planning (2003)
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    Publication Date: 2020-02-11
    Description: The UMTS radio network planning problem poses the challenge of designing a cost-effective network that provides users with sufficient coverage and capacity. We describe an optimization model for this problem that is based on comprehensive planning data of the EU project MOMENTUM. We present heuristic mathematical methods for this realistic model, including computational results.
    Keywords: ddc:000
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  • 24
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    Assessing Capacity Improvements by Relaying in Cellular Networks (2003)
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    Publication Date: 2014-02-26
    Description: Relaying -- allowing multiple wireless hops -- is a protocol extension for cellular networks conceived to improve data throughput. Its benefits have only been quantified for small example networks. For assessing its general potential, we define a complex resource allocation\slash{}scheduling problem. Several mathematical models are presented for this problem; while a time-expanded MIP approach turns out intractable, a sophisticated column generation scheme leads to good computational results. We thereby show that for selected cases relaying can increase data throughput by 30\% on the average.
    Keywords: ddc:000
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  • 25
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    Minimum Converter Wavelength Assignment in All-Optical Networks (2003)
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    Publication Date: 2014-02-26
    Description: Finding conflict-free wavelength assignments with a minimum number of required conversions for a routing of the lightpaths is one of the important tasks within the design of all-optical networks. We consider this problem in multi-fiber networks with different types of WDM systems. We give a detailed description of the problem and derive its theoretical complexity. For practical application, we propose several sequential algorithms to compute appropriate wavelength assignments. We also perform computational experiments to evaluate their performance. For the iterative algorithms, we identify characteristic patterns of progression. Two of these algorithms qualify for application in practice.
    Keywords: ddc:000
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  • 26
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    Rigid body docking for Virtual Screening (2003)
    Details
    Publication Date: 2014-09-30
    Description: A recently developed algorithm allows Rigid Body Docking of ligands to proteins, regardless of the accessibility and location of the binding site. The Docking procedure is divided into three subsequent optimization phases, two of which utilize rigid body dynamics. The last one is applied with the ligand already positioned inside the binding pocket and accounts for full flexibility. Initially, a combination of geometrical and force-field based methods is used as a Coarse Docking strategy, considering only Lennard-Jones interactions between the target and pharmaceutically relevant atoms or functional groups. The protein is subjected to a Hot Spot Analysis, which reveals points of high affinity in the protein environment towards these groups. The hot spots are distributed into different subsets according to their group affiliation. The ligand is described as a complementary point set, consisting of the same subsets. Both sets are matched in $\mathrm{I\!R}^{3}$, by superimposing members of the same subsets. In the first instance, steric inhibition is nearly neglected, preventing the system's trajectory from trapping in local minima and thus from finding false positive solutions. Hence the exact location of the binding site can be determined fast and reliably without any additional information. Subsequently, errors resulting from approximations are minimized via finetuning, this time considering both Lennard-Jones and Coulomb forces. Finally, the potential energy of the whole complex is minimized. In a first evaluation, results are rated by a reduced scoring function considering only noncovalent interaction energies. Exemplary Screening results will be given for specific ligands.
    Keywords: ddc:000
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    Integrated Optimization of Hardware Configuration and Capacity. Dimensioning in SDH and opaque WDM networks (2003)
    Details
    Publication Date: 2014-02-26
    Description: We suggest a new model for the design of telecommunication networks which integrates decisions about the topology, configuration of the switching hardware, link dimensioning, and protected routing of communication demands. Applying the branch-and-cut-algorithm implemented in our network planning and optimization tool DISCNET, we demonstrate that real-world based network planning instances of such an enhanced model can be solved.
    Keywords: ddc:000
    Language: English
    Type: reportzib , doc-type:preprint
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    Verteilter Dokumenten-Speicher, Erfahrungen mit den Kluwer-Daten des Friedrich-Althoff-Konsortiums (2003)
    Details
    Publication Date: 2020-02-11
    Description: Dieser Bericht beschreibt die Erfahrungen und Schlussfolgerungen,die im Rahmen der VDS-Vorstudie bei der Speicherung der vom Friedrich-Althoff-Konsortium lizenzierten Zeitschriften des Kluwer-Verlages gewonnen wurden.
    Keywords: ddc:000
    Language: German
    Type: reportzib , doc-type:preprint
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    Endnutzerbasierte Online-Fernleihe im KOBV - Kurzbeschreibung (2003)
    Details
    Publication Date: 2020-11-13
    Description: Der KOBV setzt für die endnutzerbasierte Online-Fernleihe den Sisis ZFL-Server (Zentraler Fernleih-Server) ein. Mit dem Einsatz des ZFL-Servers können in den Bibliotheken echte Rationalisierungseffekte erzielt werden: Der Server ist in der Lage, Fernleih-Bestellungen an lokale Systeme zu übergeben, so dass sie im lokalen System automatisch - ohne Eingreifen von Bibliotheksmitarbeitern - weiterverarbeitet werden können. Im KOBV können derzeit Sisis- und Aleph-Lokalsysteme diese Schnittstelle voll bedienen. Andere Bibliothekssysteme im KOBV, die diese Schnittstelle nicht bedienen können, werden mittels eines E-Mail-Verfahrens in die Online-Fernleihe integriert. Die vorliegende Kurzbeschreibung der Online-Fernleihe im KOBV soll - im Gegensatz zur Spezifikation, die möglichst vollständig sein sollte - einen leicht verständlichen Einblick in die Abläufe der Online-Fernleihe vermitteln. Nach einem Überblick über zu erwartende Rationalisierungseffekte ist der Ablauf einer Online-Fernleih-Bestellung - veranschaulicht durch eine Graphik mit dem technischen Aufbau im KOBV - kurz dargestellt. \vspace{6mm} {\it Hinweis:} Die von einer Arbeitsgruppe des KOBV erstellte Spezifikation zur Online-Fernleihe ist als ZIB Report 02-30 auf dem Preprint-Server des ZIB veröffentlicht. Siehe: Monika Kuberek (Red.) {\begin{rawhtml} 〈a href="http://www.zib.de/Publications/Reports/ZR-02-30.pdf"〉 〈i〉 Spezifikation für eine Verbund-Fernleih-Software im KOBV〈/i〉 〈/a〉 \end{rawhtml}}
    Keywords: ddc:000
    Language: German
    Type: reportzib , doc-type:preprint
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    Improved Perron Cluster Analysis (2003)
    Details
    Publication Date: 2014-02-26
    Description: The problem of clustering data can often be transformed into the problem of finding a hidden block diagonal structure in a stochastic matrix. Deuflhard et al. have proposed an algorithm that state s the number $k$ of clusters and uses the sign structure of $k$ eigenvectors of the stochastic matrix to solve the cluster problem. Recently Weber and Galliat discovered that this system of eigenvectors can easily be transformed into a system of $k$ membership functions or soft characteristic functions describing the clusters. In this article we explain the corresponding cluster algorithm and point out the underlying theory. By means of numerical examples we explain how the grade of membership can be interpreted.
    Keywords: ddc:000
    Language: English
    Type: reportzib , doc-type:preprint
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    Zur Zugriffskontrolle im KOBV (2003)
    Details
    Publication Date: 2014-02-26
    Description: Mit der Entwicklung des KOBV-Informationsportals soll den Benutzern in der Region Berlin-Brandenburg ein verbesserter Zugang zu Informationsressourcen geboten werden. Einen wesentlichen Anteil diese Auf der Grundlage der Analyse der Rahmenbedingungen werden Anforderungen an die Zugriffskontrolle im KOBV definiert und Lösungsmöglichkeiten auf der Ebene allgemeiner Modelle diskutiert.
    Keywords: ddc:000
    Language: German
    Type: reportzib , doc-type:preprint
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    Navigation in the KOBV-Informationsportal Conceptual View (2003)
    Details
    Publication Date: 2014-02-26
    Description: The KOBV Informationsportal aims to be a universal gateway to the sources of information hosted by the partner libraries from the Berlin-Brandenburg area. Due to the large number of these sources, an intuitive navigation is an essential component of the portal. The navigation-component should preserve the partner libraries? independence and overcome their administrative and technical differences. This paper proposes a collection-level navigation with four dimensions: the sources? subject areas (e.g. the first two levels of DDC), the sources? type (e.g. e-journals, databases, OPACs, etc.), the sources? location (e.g. Berlin, Brandenburg) / the library that hosts that source and the sources? accessing state (e.g. free, restricted, etc.).
    Keywords: ddc:000
    Language: English
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    Polynomial Inequalities Representing Polyhedra (2003)
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    Publication Date: 2014-02-26
    Description: Our main result is that every n-dimensional polytope can be described by at most (2n-1) polynomial inequalities and, moreover, these polynomials can explicitly be constructed. For an n-dimensional pointed polyhedral cone we prove the bound 2n-2 and for arbitrary polyhedra we get a constructible representation by 2n polynomial inequalities.
    Keywords: ddc:000
    Language: English
    Type: reportzib , doc-type:preprint
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    The final NETLIB-LP results (2003)
    Details
    Publication Date: 2020-02-11
    Description: The NETLIB has now served for 18 years as a repository of LP problem instances. From the beginning to the present day there was some uncertainness about the precise values of the optimal solutions. We implemented a program using exact rational arithmetic to compute proofs for the feasibility and optimality of an LP solution. This paper reports the \emph{exact} optimal objective values for all NETLIB problems.
    Keywords: ddc:000
    Language: English
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    Dust formation in brown dwarf atmospheres under conditions of driven turbulence (2003)
    Details
    Publication Date: 2014-02-26
    Description: Based on the knowledge gained from direct numerical simulations which are only possible in the microscale regime, a concept of driven turbulence is presented which allows to enter the mesoscopic scale regime. Here, dust formation under stochastic hydro- and thermodynamic conditions is studied: constructively superimposed stochastic waves initiate dust formation by the creation of singular nucleation events. It, hence, results a varying mean grain size and dust density in space and time. The newly formed dust changes the thermodynamic behavior from almost isotherm to adiabatic and chemically depletes the gas phase.
    Keywords: ddc:000
    Language: English
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    Kosten- und Qualitätsoptimierung in Kommunikationsnetzen (2003)
    Details
    Publication Date: 2014-11-11
    Description: Der scharfe Wettbewerb innerhalb der Telekommunikationsbranche zwingt die Netzbetreiber dazu, ihre Investitionen genau zu planen und immer wieder Einsparungsmanahmen durchzuführen. Gleichzeitig ist es jedoch wichtig, die Qualität der angebotenen Dienste zu verbessern, um neue Kunden zu gewinnen und langfristig an sich zu binden. Die mathematische Optimierung bietet sich für viele solcher Aufgabenstellungen als hervorragend geeignetes Planungswerkzeug an. Ziel dieses Artikels ist es, ihre Methodik und ihre Anwendung speziell zur Kosten- und Qualitätsoptimierung in Kommunikationsnetzen vorzustellen. Anhand von vier konkreten Planungsaufgaben aus dem Bereich der Festnetzplanung wird aufgezeigt, wie sich komplexe Zusammenhänge in flexiblen mathematischen Modellen abbilden lassen und welche Verfahren zur automatisierten Bearbeitung der Probleme eingesetzt werden können. Die hier vorgestellten Methoden zeichnen sich insbesondere dadurch aus, dass sie neben hochwertigen Lösungen auch eine Qualittsgarantie liefern, mit der sich die Lsungen fundiert bewerten lassen. Die dokumentierten Ergebnisse aus verschiedenen Industrieprojekten belegen die Eignung und Güte der mathematischen Optimierung für die Praxis.
    Keywords: ddc:000
    Language: German
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    Dust in Brown Dwarfs IV. Dust formation and driven turbulence on mesoscopic scales (2003)
    Details
    Publication Date: 2014-02-26
    Description: Dust formation {in brown dwarf atmospheres} is studied by utilizing a model for driven turbulence in the mesoscopic scale regime. We apply a pseudo-spectral method where waves are created and superimposed {within} a {limited} wavenumber interval. The turbulent kinetic energy distribution follows the Kolmogoroff spectrum which is assumed to be the most likely value. Such superimposed, stochastic waves may occur in a convectively active environment. They cause nucleation fronts and nucleation events and thereby initiate the dust formation process which { continues until} all condensible material is consumed. Small disturbances {are found to} have a large impact on the dust forming system. An initially dust-hostile region, which may originally be optically thin, becomes optically thick in a patchy way showing considerable variations in the dust properties during the formation process. The dust appears in lanes and curls as a result of the interaction with waves, i.e. turbulence, which form larger and larger structures with time. Aiming on a physical understanding of the variability of brown dwarfs, related to structure formation in substellar atmospheres, we work out first necessary criteria for small-scale closure models to be applied in macroscopic simulations of dust forming astrophysical systems.
    Keywords: ddc:000
    Language: English
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    The multi-scale dust formation in substellar atmospheres (2003)
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    Publication Date: 2014-02-26
    Description: Substellar atmospheres are observed to be irregularly variable for which the formation of dust clouds is the most promising candidate explanation. The atmospheric gas is convectively unstable and, last but not least, colliding convective cells are seen as cause for a turbulent fluid field. Since dust formation depends on the local properties of the fluid, turbulence influences the dust formation process and may even allow the dust formation in an initially dust-hostile gas. A regime-wise investigation of dust forming substellar atmospheric situations reveals that the largest scales are determined by the interplay between gravitational settling and convective replenishment which results in a dust-stratified atmosphere. The regime of small scales is determined by the interaction of turbulent fluctuations. Resulting lane-like and curled dust distributions combine to larger and larger structures. We compile necessary criteria for a subgrid model in the frame of large scale simulations as result of our study on small scale turbulence in dust forming gases.
    Keywords: ddc:000
    Language: English
    Type: reportzib , doc-type:preprint
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    HelmPole - A finite element solver for scattering problems on unbounded domains: Implementation based on PML (2003)
    Details
    Publication Date: 2019-01-24
    Description: The solution of scattering problems described by the Helmholtz equation on unbounded domains is of importance for a wide variety of applications, for example in electromagnetics and acoustics. An implementation of a solver for scattering problems based on the programming language Matlab is introduced. The solver relies on the finite-element-method and on the perfectly-matched-layer-method, which allows for the simulation of scattering problems on complex geometries surrounded by inhomogeneous exterior domains. This report gives a number of detailed examples and can be understood as a user manual to the freely accessible code of the solver HelmPole.
    Keywords: ddc:000
    Language: English
    Type: reportzib , doc-type:preprint
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    Progressive Retrieval and Hierarchical Visualization of Large Remote Data (2003)
    Details
    Publication Date: 2020-03-09
    Description: \noindent The size of data sets produced on remote supercomputer facilities frequently exceeds the processing capabilities of local visualization workstations. This phenomenon increasingly limits scientists when analyzing results of large-scale scientific simulations. That problem gets even more prominent in scientific collaborations, spanning large virtual organizations, working on common shared sets of data distributed in Grid environments. In the visualization community, this problem is addressed by distributing the visualization pipeline. In particular, early stages of the pipeline are executed on resources closer to the initial (remote) locations of the data sets. \noindent This paper presents an efficient technique for placing the first two stages of the visualization pipeline (data access and data filter) onto remote resources. This is realized by exploiting the ``extended retrieve'' feature of GridFTP for flexible, high performance access to very large HDF5 files. We reduce the number of network transactions for filtering operations by utilizing a server side data processing plugin, and hence reduce latency overhead compared to GridFTP partial file access. The paper further describes the application of hierarchical rendering techniques on remote uniform data sets, which make use of the remote data filtering stage.
    Keywords: ddc:000
    Language: English
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    The Potential of Relaying in Cellular Networks (2003)
    Details
    Publication Date: 2014-02-26
    Description: Relaying is a protocol extension for cellular wireless computer networks; in order to utilize radio resources more efficiently, several hops are allowed within one cell. This paper investigates the principle potential of relaying by casting transmission scheduling as a mathematical optimization problem, namely, a linear program. We analyze the throughput gains showing that, irrespective of the concrete scheduling algorithm, performance gains of up to 30\% on average for concrete example networks are achievable.
    Keywords: ddc:000
    Language: English
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    Critical and Anticritical Edges with respect to Perfectness (2003)
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    Publication Date: 2014-02-26
    Description: We call an edge $e$ of a perfect graph $G$ critical if $G-e$ is imperfect and call $e$ anticritical if $G+e$ is imperfect. The present paper surveys several questions in this context. We ask in which perfect graphs critical and anticritical edges occur and how to detect such edges. The main result by [{\sl Wagler, PhD thesis 2000}] shows that a graph does not admit any critical edge if and only if it is Meyniel. The goal is to order the edges resp.~non-edges of certain perfect graphs s.t. deleting resp.~adding all edges in this order yields a sequence of perfect graphs only. Results of [{\sl Hayward 1985}] and [{\sl Spinrad & Sritharan 1995}] show the existence of such edge orders for weakly triangulated graphs; the line-perfect graphs are precisely these graphs where all edge orders are perfect [{\sl Wagler 2001}]. Such edge orders cannot exist for every subclass of perfect graphs that contains critically resp.~anticritically perfect graphs where deleting resp.~adding an arbitrary edge yields an imperfect graph. We present several examples and properties of such graphs, discuss constructions and characterizations from [{\sl Wagler 1999, Wagler PhD thesis 2000}]. An application of the concept of critically and anticritically perfect graphs is a result due to [{\sl Hougardy & Wagler 2002}] showing that perfectness is an elusive graph property.
    Keywords: ddc:000
    Language: English
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    Accelerating Hasenbusch's Acceleration of Hybrid Monte Carlo (2003)
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    Publication Date: 2014-02-26
    Description: Hasenbusch has proposed splitting the pseudo-fermionic action into two parts, in order to speed-up Hybrid Monte Carlo simulations of QCD. We have tested a different splitting, also using clover-improved Wilson fermions. An additional speed-up between 5 and 20\% over the original proposal was achieved in production runs.
    Keywords: ddc:000
    Language: English
    Type: reportzib , doc-type:preprint
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    Safe separators for treewidth (2003)
    Details
    Publication Date: 2014-11-10
    Description: A set of vertices $S\subseteq V$ is called a safe separator for treewidth, if $S$ is a separator of $G$, and the treewidth of $G$ equals the maximum of the treewidth over all connected components $W$ of $G-S$ of the graph, obtained by making $S$ a clique in the subgraph of $G$, induced by $W\cup S$. We show that such safe separators are a very powerful tool for preprocessing graphs when we want to compute their treewidth. We give several sufficient conditions for separators to be safe, allowing such separators, if existing, to be found in polynomial time. In particular, every minimal separator of size one or two is safe, every minimal separator of size three that does not split off a component with only one vertex is safe, and every minimal separator that is an almost clique is safe; an almost clique is a set of vertices $W$ such that there is a $v\in W$ with $W-\{v\}$ a clique. We report on experiments that show significant reductions of instance sizes for graphs from proba! bilistic networks and frequency assignment.
    Keywords: ddc:000
    Language: English
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    Interior Point Methods in Function Space (2003)
    Details
    Publication Date: 2019-01-29
    Description: A primal-dual interior point method for optimal control problems is considered. The algorithm is directly applied to the infinite dimensional problem. Existence and convergence of the central path are analyzed, and linear convergence of a short step pathfollowing method is established.
    Keywords: ddc:000
    Language: English
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    Triangulated Manifolds with Few Vertices: Geometric 3-Manifolds (2003)
    Details
    Publication Date: 2014-02-26
    Description: We explicitly construct small triangulations for a number of well-known $3$-dimensional manifolds and give a brief outline of some aspects of the underlying theory of $3$-manifolds and its historical development.
    Keywords: ddc:000
    Language: English
    Type: reportzib , doc-type:preprint
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    Lastbalancierung in Peer-to-Peer Systemen (2003)
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    Publication Date: 2016-06-30
    Description: Peer-to-Peer (P2P) Systeme werden u.a. zur Verwaltung von großen Datenmengen benutzt, die auf verschiedene Rechner verteilt sind. Benutzern soll damit der Zugriff auf Daten innerhalb des Systems leicht ermöglicht werden. Damit in P2P Systemen die Daten effizient verteilt und gesucht werden können, existieren Distributed Hash Tables. Distributed Hash Tables (DHT) sind eine Methode, um globale Informationen persistent speichern zu können. Der Wertebereich der Hashfunktion, welche die zu veröffentlichenden Einträge auf Werte abbildet, wird in Abschnitte aufgeteilt, die einzelnen Knoten zugeteilt werden. Die meisten DHTs haben aber ein Problem bei der Verteilung der Last. Die verschiedenen DHT Systeme beruhen meist auf einem identischen Ansatz der Lastverteilung. Die Last wird nur mit Hilfe einer Hashfunktion verteilt. Es wird davon ausgegangen, dass diese Funktion die Last gleichmäßig verteilt. Im Rahmen dieser Arbeit wurde ein Verfahren zur Last Verteilung entwickelt, simuliert und implementiert. Bei dem Verfahren wird die Last wie bei der Verteilung von Wärme an die Umgebung abgegeben. Es wird mit existierenden Lastbalancierungsalgorithmen verglichen. Mit diesem neuen Verfahren ist es möglich, Last in DHTs besser zu verteilen ohne große Änderungen an den DHTs vorzunehmen. Es wird gezeigt, wie mit dem Verfahren zusätzlich die Fehlertoleranz des P2P Systems erhöht werden kann.
    Description: One of the many uses of Peer-to-Peer (P2P) systems is the administration of large data sets that are distributed across different computers, with the goal of facilitating user access to files within the system. Distributed Hash Tables (DHT) are designed to enable the efficient distribution and search of files, by allowing global information to be persistently stored. The range of values of the hash function (the possible entries in the published hash table) are assigned to individual nodes. Most DHTs, however, have a problem with load distribution. The various DHT systems usually operate by distributing load equally among nodes. Thus the load is distributed using the help of the hash function. One assumes this function distributes the load evenly. In the context of this work a method of distributing load has been developed, simulated and implemented. With this method load is transferred in a fashion analogous to the dissipation of heat into the environment. Comparisons with existing algorithms for load balancing are drawn. With the new procedure it is possible to better distribute load in DHTs without requiring major changes to the DHTs themselves. It is shown that with the procedure the fault tolerance of P2P systems may also be increased.
    Keywords: ddc:000
    Language: German
    Type: masterthesis , doc-type:masterThesis
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    Robust Perron Cluster Analysis in Conformation Dynamics (2003)
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    Publication Date: 2014-02-26
    Description: The key to molecular conformation dynamics is the direct identification of metastable conformations, which are almost invariant sets of molecular dynamical systems. Once some reversible Markov operator has been discretized, a generalized symmetric stochastic matrix arises. This matrix can be treated by Perron cluster analysis, a rather recent method involving a Perron cluster eigenproblem. The paper presents an improved Perron cluster analysis algorithm, which is more robust than earlier suggestions. Numerical examples are included.
    Keywords: ddc:000
    Language: English
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    Demand-wise Shared Protection for Meshed Optical Networks (2003)
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    Publication Date: 2014-11-11
    Description: In this paper, a new shared protection mechanism for meshed optical networks is presented. Significant network design cost reductions can be achieved in comparison to the well-known 1+1 protection scheme. Demand-wise Shared Protection (DSP) bases on the diversification of demand routings and exploits the network connectivity to restrict the number of backup lightpaths needed to provide the desired level of prorection. Computational experiments approve the benefits of the concept DSP for cost efficient optical network designs.
    Keywords: ddc:000
    Language: English
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    Simulation of the Human Mandible: Comparison of Bone Mineral Density and Stress/Strain Profiles due to Masticatory Muscles' Traction (2003)
    Details
    Publication Date: 2019-05-10
    Description: The correlation of the inner architecture of bone and its functional loading was already stated by Wolff in 1892. Our objective is to demonstrate this interdependence in the case of the human mandible. For this purpose, stress/strain profiles occuring at a human lateral bite were simulated. Additionally, by a combination of computer graphics modules, a three--dimensional volumetric visualization of bone mineral density could be given. Qualitative correspondences between the density profile of the jaw and the simulated stress/strain profiles could be pointed out. In the long run, this might enable the use of the simulation for diagnosis and prognosis. The solution of the underlying partial differential equations describing linear elastic material behaviour was provided by an adaptive finite element method. Estimates of the discretization errors, local grid refinement, and multilevel techniques guaranteed the reliability and efficiency of the method.
    Keywords: ddc:000
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    MoDySim - A parallel dynamical UMTS simulator (2003)
    Details
    Publication Date: 2014-02-26
    Description: UMTS is a 3rd generation mobile telecommunication system which enables multi-service and multi-bit rate communication going beyond the possibilities of previous systems. The simulator MoDySim models UMTS in great detail. Characteristics of UMTS such as soft hand-over and the interdependency of load and capacity among neighbouring cells are challenges for the parallelisation of such a system. In this paper we explain how the software was parallelised and present performance results of a UMTS simulation for the city of Berlin.
    Keywords: ddc:000
    Language: English
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    A numerical reinvestigation of the Aoki phase with $N_f=2$ Wilson fermions at zero temperature (2003)
    Details
    Publication Date: 2014-02-26
    Description: We report on a numerical reinvestigation of the Aoki phase in lattice QCD with two flavors of Wilson fermions where the parity-flavor symmetry is spontaneously broken. For this purpose the Hybrid Monte Carlo algorithm was used and an explicit symmetry-breaking source term $h\bar{\psi} i \gamma_{5} \tau^{3}\psi$ was added to the Wilson fermion action. The order parameter $\langle\bar{\psi}i\gamma_{5}\tau^{3}\psi\rangle$ was studied at several values of $(\beta,\kappa,h)$ on lattices of sizes $4^4$ to $12^4$. Our largest lattices can be considered as infintely large allowing to extrapolate to $h=0$. The existence of a parity-flavor-breaking phase can be confirmed at $\beta=4.0$ and $\beta=4.3$ while we find no sign of parity-flavor-breaking at $\beta=4.6$ and $\beta=5.0$.
    Keywords: ddc:000
    Language: English
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  • 53
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    Clustering by using a simplex structure (2003)
    Details
    Publication Date: 2014-02-26
    Description: In this paper we interpret clustering as a mapping of data into a simplex. If the data itself has simplicial struture this mapping becomes linear. Spectral analysis is an often used tool for clustering data. We will show that corresponding singular vectors or eigenvectors comprise simplicial structure. Therefore they lead to a cluster algorithm, which consists of a simple linear mapping. An example for this kind of algorithms is the Perron cluster analysis (PCCA). We have applied it in practice to identify metastable sets of molecular dynamical systems. In contrast to other algorithms, this kind of approach provides an a priori criterion to determine the number of clusters. In this paper we extend the ideas to more general problems like clustering of bipartite graphs.
    Keywords: ddc:000
    Language: English
    Type: reportzib , doc-type:preprint
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  • 54
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    Ein neues Verfahren zur Lösung des Streuproblems der Maxwell-Gleichungen (2003)
    Details
    Publication Date: 2016-06-09
    Keywords: ddc:000
    Language: German
    Type: masterthesis , doc-type:masterThesis
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  • 55
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    Jahresbericht 2002 (2003)
    Details
    Publication Date: 2019-10-24
    Keywords: ddc:000
    Language: German
    Type: annualzib , doc-type:report
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  • 56
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    Semantic Annotation in Mathematics and Math-Net (2003)
    Details
    Publication Date: 2022-04-11
    Description: The Web of the future will provide a huge amount of information. We need better ways for dealing with and managing the information. A qualified semantic annotation of the information plays a key role for the Web of the future. This article gives an overview about the efforts of the mathematical community to build up a distributed and open information and communication system for mathematics: the Math-Net. The Math-Net Initiative has developed metadata schemas for some classes of Web resources which are relevant in mathematics. Math-Net Services process this information and enable the user to efficiently search and access the information.
    Keywords: ddc:000
    Language: English
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  • 57
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    A new Finite Element realization of the Perfectly Matched Layer Method for Helmholtz scattering problems on polygonal domains in 2D (2003)
    Details
    Publication Date: 2022-07-07
    Description: In this paper we propose a new finite element realization of the Perfectly Matched Layer method (PML-method). Our approach allows to deal with arbitrary shaped polygonal domains and with certain types of inhomogeneous exterior domains. Among the covered inhomogeneities are open waveguide structures playing an essential role in integrated optics. We give a detailed insight to implementation aspects. Numerical examples show exponential convergence behavior to the exact solution with the thickness of the PML sponge layer.
    Keywords: ddc:000
    Language: English
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  • 58
    Electronic Resource
    Electronic Resource
    Transcatheter therapy of gastric cancer metastatic to the liver: preliminary results (2000)
    Springer
    Journal of gastroenterology 35 (2000), S. 907-911 
    Details
    ISSN: 1435-5922
    Keywords: Key words: gastric cancer ; liver neoplasms ; secondary ; interventional radiology ; chemotherapy ; chemoembolization ; therapeutic
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract: Little is known about the effectiveness of transcatheter chemotherapy in liver metastases from gastric cancer. The aim of this study was to evaluate the initial results of hepatic artery infusion and oily chemoembolization in these liver secondaries. Courses of transcatheter arterial infusion with 5-fluorouracil/doxorubicin (12 patients) and oily chemoembolization with doxorubicin-in-iodized oil and gelatin sponge (12 patients) were performed in 24 patients with histologically proven unresectable gastric cancer liver metastases. A positive effect of treatment (partial response + stabilization) was seen in 92% of the patients after chemoinfusion and in 50% after chemoembolization. The 1- and 2-year actuarial survival rates were 92% and 53% for infusion vs 50% and 17% for chemoembolization, respectively (log-rank test, P = 0.0009). For patients who had already died, the mean survival was 19.2 months vs 9.5 months (Student's t-test, P 〈 0.05) with median survivals of 23 months vs 8 months, respectively. The results with arterial infusion were very close to those reported for liver resection. Transcatheter therapy appears to be useful for the palliation of unresectable liver metastases from gastric cancer. If regional chemotherapy is used, arterial infusion should be the first-choice treatment, with oily chemoembolization being reserved for patients who do not respond to infusion.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s005350070004
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  • 59
    Electronic Resource
    Electronic Resource
    Docetaxel (Taxotere®)–cisplatin (TC): An effective drug combination in gastric carcinoma (2000)
    Springer
    Annals of oncology 11 (2000), S. 301-306 
    Details
    ISSN: 1569-8041
    Keywords: chemotherapy ; docetaxel ; gastric cancer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Purpose:A multi-centric trial was performed to explore theclinical activity, in terms of response and toxicity (primary objectives),duration of response and survival (secondary objectives), of docetaxel withcisplatin in advanced gastric cancer (AGC). Patients and methods:Patients with measurable unresectable and/ormetastatic gastric carcinoma, performance status ≤1, normal hematological,hepatic and renal functions and not pretreated for advanced disease bychemotherapy received up to eight cycles of TC (docetaxel 85 mg/m2d1, cisplatin 75 mg/m2 d1) q3w. Dose escalation to 100mg/m2 was performed in five patients and was discontinued forexcessive toxicity. Results:Forty-eight patients were accrued. A median of 5cycles/patient was given. We observed 2 complete and 25 partial responses foran overall intent to treat response rate of 56% (95% CI:41%–71%). Twelve patients had stable disease for ≥9weeks (3 cycles). The median time to progression and overall survival were 6.6and 9 months, respectively. Grade ≥3 toxicities were neutropenia81%, anemia 32%, thrombocytopenia 4%, alopecia36%, fatigue 9%, mucositis 9%, diarrhea 6%,nausea/vomiting 4%, neurologic 2%, and one anaphylaxisprecluding treatment administration. We recorded nine episodes of non-fatalfebrile neutropenia in eight patients, two of them with docetaxel at 100mg/m2. There were no direct treatment-related deaths. Conclusions:TC is active in AGC with a high response rate in amulticentric trial. Despite its hematotoxicity, this regimen is well toleratedand can be recycled as originally planned in 78% of the cases. Theseresults may serve as basis for further developments of docetaxel containingregimens in this disease.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008342013224
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  • 60
    Electronic Resource
    Electronic Resource
    A phase I–II study of concomitant chemoradiotherapy with paclitaxel (one-hour infusion), 5-fluorouracil and hydroxyurea with granulocyte colony stimulating factor support for patients with poor prognosis head and neck cancer (2000)
    Springer
    Annals of oncology 11 (2000), S. 721-728 
    Details
    ISSN: 1569-8041
    Keywords: chemotherapy ; concomitant chemoradiotherapy ; head and neck cancer ; paclitaxel ; radiation ; reirradiation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background:Concomitant chemoradiotherapy is an effectivetreatment modality for advanced head and neck cancer, but improved regimensare needed. We sought to define the toxicities, recommended phase II dose, andoutcome of a combination chemotherapy regimen with concomitanthyperfractionated radiotherapy in patients with poor prognosis cancers of thehead and neck, including those having received prior curative intentradiotherapy. Patients and methods:From 1995 until 1997, 54 patients weretreated, 25 of whom had received a prior full course of radiotherapy to thehead and neck. Patients were treated with 5-fluorouracil (5-FU) 600mg/m2/day continuous infusion × 5 days (days 1–5),hydroxyurea, 500 mg p.o. bid × 11 doses (days 1–6) and paclitaxel(60–150 mg/m2) by one-hour infusion on day 2 using a doseescalation strategy. Radiotherapy was given concomitantly on days 2–6,150 cGy bid. Each of 4–5 cycles was delivered every other week. Results:The MTD of paclitaxel was 100 mg/m2. Theregimen was feasible; radiotherapy was delivered at a median of 7300 cGy and83% of patients received ≥80% planned dose intensity.Hematological toxicity, with granulocyte colony stimulating factor, was verymild. Dose limiting toxicities were mucositis and dermatitis. Despite poorprognosis, two-year survival was 45%. Conclusions:The recommended phase II dose of this regimen is 5-FU600 mg/m2/day × 120 hours (days 1–5), hydroxyurea 500mg p.o. b.i.d. × 11 doses (days 1–6), paclitaxel 100mg/m2 over one hour on day 2, and radiotherapy 150 cGy b.i.d. days2–6. Concomitant chemotherapy and re-irradiation was feasible on thisprotocol and resulted in long-term survival in patients without other curativeintent options.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008324131519
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  • 61
    Electronic Resource
    Electronic Resource
    Spontaneous pneumothorax in malignancy: A case report and review of the literature (2000)
    Springer
    Annals of oncology 11 (2000), S. 887-889 
    Details
    ISSN: 1569-8041
    Keywords: chemotherapy ; lung metastases ; spontaneous pneumothorax
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background:Pneumothorax occurring in the absence of obvious lungdisease is defined as spontaneous pneumothorax. Spontaneous pneumothoraxoccurs in a variety of settings in patients with malignancies. Patients and methods:We present a case report of spontaneouspneumothorax in malignancy and review the literature. Results:No correlation was found between the occurrence ofpneumothorax with age, sex or smoking history. Pneumothorax occurred with avariety of primary tumors. However it was always associated with lungmetastases or lung involvement with tumor. In certain cases the metastaseswere detected after the occurrence of pneumothorax. Conclusions:The occurrence of pneumothorax in a patient withmalignancy should prompt a search for lung metastases.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008323632078
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  • 62
    Electronic Resource
    Electronic Resource
    Paclitaxel and carboplatin in combination with gemcitabine: A phase I–II trial in patients with advanced non-small-cell lung cancer (2000)
    Springer
    Annals of oncology 11 (2000), S. 1421-1426 
    Details
    ISSN: 1569-8041
    Keywords: carboplatin ; chemotherapy ; gemcitabine ; non-small-cell lung cancer ; paclitaxel
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background:The combination of paclitaxel (P) and carboplatin (C)is an effective treatment for advanced NSCLC. Gemcitabine (G) is an active newdrug. We planned a phase I study to find the maximum tolerated dose (MTD) ofthe PCG combination. A phase II study was subsequently conducted to evaluatethe activity and toxicity of PCG. Patients and methods:Forty-five patients entered the study.Twenty-eight had stage IIIA–B disease, 17 stage IV. In the phase Istudy, with a fixed dose of C at AUC = 6 on day 1, P was escalated usingincrements of 25 mg/m2 starting from 175 mg/m2 on day1 and G with increments of 200 mg/m2 starting from 800mg/m2 on day 1 and 8. Results:Fourteen patients entered the phase I study. The MTD wasreached at P 200 mg/m2, C AUC = 6 and G 1000 mg/m2.Neutropenic fever and grade 3 diarrhea were the dose limiting toxicities.Thirty-one patients were treated in the phase II study with P 175mg/m2, C AUC = 6 and G 1000 mg/m2. Response rate was57% (68% in stage III and 47% in stage IV).Myelosuppression was the main toxicity, with grade 3–4 leukopeniaoccurring in 35% of cases. Grade 3 anemia was observed in 24%of cases and grade 3–4 thrombocytopenia occurred in 34% ofpatients. Non-hematological toxicity was mild. Median survival and one-yearactuarial survival were 20.5 months and 74% for stage III and 11.5months and 47% for stage IV. Conclusions:PCG is a promising regimen for treating advancedNSCLC. A phase III study comparing PCG to paclitaxel plus carboplatin inadvanced NSCLC is ongoing. On the other hand, we are planning to introduce thePCG regimen in the treatment of stage II–III patients in the setting ofa multimodality treatment.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1026527004596
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  • 63
    Electronic Resource
    Electronic Resource
    NCIC–CTG phase II study of gemcitabine in patients with malignant glioma (IND.94) (2000)
    Springer
    Annals of oncology 11 (2000), S. 315-318 
    Details
    ISSN: 1569-8041
    Keywords: chemotherapy ; gemcitabine ; malignant glioma
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Purpose:We conducted a phase II multicentre study of gemcitabinein patients with anaplastic astrocytoma and glioblastoma multiforme at firstrelapse. Patients and methods:Patients with anaplastic astrocytoma orglioblastoma multiforme receiving a stable dose of steroids and ECOGperformance status ≤3 were eligible for this study at the time of firstrelapse. One adjuvant chemotherapy regimen was permissible. Patients receivedgemcitabine 1000 mg/m2 i.v. weekly × 3, repeated on afour-weekly cycle. Results:Of 20 patients enrolled, 15 were evaluable for response,19 for non-hematological toxicity and 18 for hematological toxicity. Sevenpatients had anaplastic astrocytoma (AA) and twelve glioblastoma multiforme(GBM). Age ranged from 28–71 years (median 50). Fifteen patientsdiscontinued therapy due to disease progression. The median number of cyclesadministered was 1 (range 1–11); only two patients received more thanthree cycles. Hematologic toxicity was acceptable and no grade 4 toxicity wasseen. One patient developed Pneumocystispneumonia and eventualpulmonary embolism; one died of gastric hemorrhage related to steroid therapy.No objective responses were seen. Nine patients had stable disease (medianduration 2.7 months, range 0.9–11.2). Conclusions:Gemcitabine given in this dose and schedule seemswell tolerated but is not active in patients with recurrent high-gradegliomas.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008336607135
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  • 64
    Electronic Resource
    Electronic Resource
    Weekly administration of bendamustine: A phase I study in patients with advanced progressive solid tumours (2000)
    Springer
    Annals of oncology 11 (2000), S. 729-734 
    Details
    ISSN: 1569-8041
    Keywords: alkylating agents ; bendamustine ; chemotherapy ; phase I study ; solid tumours ; weekly chemotherapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background:The cytotoxic agent bendamustine combines apurine-like benzimidazol and alkylating nitrogen mustard group. The clinicallytolerated dose for single bolus bendamustine is 215 mg/m2, forfractionated therapy on four consecutive days 85 mg/m2. The maximumtolerated dose of a day 1 and 8 (q4w) 30 min infusion schedule was recentlyfound to be 160 mg/m2, mouth dryness and fatigue weredose-limiting. Our current phase I trial was designed to define therecommended dose of a new weekly short infusion schedule. Patients and methods:Patients with refractory malignant tumoursqualified for the trial after written informed consent was obtained.Bendamustine was given as a 30-min i.v. infusion weekly for up to eightconsecutive weeks. Results:Twelve patients (8 male, 4 female, median age 57.5 years,range 42–64) were enrolled in this trial. At the starting dose of 80mg/m2, two patients had dose-limiting toxicity (fatigue grade 3,mouth dryness grade 3, fever grade 4 Common Toxicity Criteria). Nodose-limiting events were observed in six patients treated at 60mg/m2. An intermediate dose level of 70 mg/m2 wasstudied in three younger, less heavily pre-treated patients, was welltolerated and not associated with dose-limiting events. Haematologicaltoxicity was mild except for grade 3–4 lymphocytopenia, occurring in 11of 12 patients. Bendamustine was found to induce long-lastingpanlymphocytopenia with predominant B-cell cytotoxicity. Conclusions:The maximum tolerated dose of weekly bendamustinegiven as a 30-min i.v. infusion is 80 mg/m2, mouth dryness, fatigueand fever are dose-limiting. The recommended dose for phase II trials is 60mg/m2.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008309911008
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  • 65
    Electronic Resource
    Electronic Resource
    A dose-finding study of liposomal daunorubicin with CVP (COP-X) in advanced NHL (2000)
    Springer
    Annals of oncology 11 (2000), S. 691-695 
    Details
    ISSN: 1569-8041
    Keywords: anthracycline ; chemotherapy ; liposomal daunorubicin ; lymphoma
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background:Standard therapy for lymphoma consists of acyclophosphamide (C), doxorubicin, vincristine (V), and prednisone (P) (CHOP)combination regimen. Liposomal daunorubicin (DaunoXome®) is an alternativeto doxorubicin for patients with lymphoma because of its more favorable safetyprofile and potentially more selective uptake in lymphoma. The objectives ofthis study were to determine the maximum tolerated dose (MTD) of liposomaldaunorubucin with CVP (COP-X) and the tolerability of the regimen in patientswith indolent lymphoma. Patients and methods:Patients with low-grade andintermediate-grade lymphoma having adequate cardiac, hepatic, and renalfunction were enrolled. Patients received C 750 mg/m2, V 1.4mg/m2 (maximum 2.0 mg), and liposomal daunorubicin 50–100mg/m2 i.v. on day 1 and P 100 mg p.o. on days 1–5. MTD wasthe liposomal daunorubicin dose associated with 20% dose-limitingtoxicity (ANC 〈500/mm3 for 〉5 days or febrile neutropenia). Results:Twenty patients, median age 59 years, were treated. Theliposomal daunorubicin MTD combined with CVP was 70–80 mg/m2,depending on patient population. No significant non-hematologic toxicityoccurred. Response rate was 44% (2 complete and 5 partial responses). Conclusions:A liposomal daunorubicin dose of 80 mg/m2in the COP-X regimen was well tolerated with little non-hematologic toxicity.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008361914894
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  • 66
    Electronic Resource
    Electronic Resource
    Efficacy of adjuvant chemotherapy after curative resection for gastric cancer: A meta-analysis of published randomised trials (2000)
    Springer
    Annals of oncology 11 (2000), S. 837-843 
    Details
    ISSN: 1569-8041
    Keywords: adjuvant ; chemotherapy ; gastric cancer ; meta-analysis ; randomised clinical trial
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background:Several studies have investigated the possible roleof the adjuvant chemotherapy after curative resection for gastric cancerfailing to show a clear indication; previous meta-analyses suggested smallsurvival benefit of adjuvant chemotherapy, but the statistical methods usedwere open to criticisms. Materials and methods:Randomised trials were identified by meansof Medline and CancerLit and by selecting references from relevant articles.Systematic review of all randomised clinical trials of adjuvant chemotherapyfor gastric cancer compared with surgery alone, published before January 2000,were considered. Pooling of data was performed using the fixed effect model.Death for any cause was the study endpoint. The hazard ratio and its95% confidence intervals (95% CI), derived according to themethod of Parmar, were the statistics chosen for summarising the relativebenefit of chemotherapyversuscontrol. Results:Overall 20 articles (21 comparisons) were considered foranalysis. Three studies used single agent chemotherapy, seven combination of5-fluorouracil (5-FU) with anthracyclin, ten combination of 5-FU withoutanthracyclines. Information on 3658 patients, 2180 deaths, was collected. Chemotherapy reduced the risk of death by 18% (hazard ratio 0.82,95% CI: 0.75–0.89, P 〈 0.001). Association ofAnthracyclines to 5-FU did not show a statistically significant improvementwhen compared with the effect of the other regimens. Conclusions:Chemotherapy produces a small survival benefit inpatients with curatively resected gastric cancer. However, taking into accountthe limitations of literature based meta-analyses, adjuvant chemotherapy isstill to be considered as an investigational approach.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008377101672
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  • 67
    Electronic Resource
    Electronic Resource
    Chromosome aberrations after etoposide containing cisplatin-based chemotherapy for malignant germ-cell tumours (2000)
    Springer
    Annals of oncology 11 (2000), S. 897-898 
    Details
    ISSN: 1569-8041
    Keywords: chemotherapy ; chromosome aberrations ; malignant germ-cell tumours
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008311532043
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  • 68
    Electronic Resource
    Electronic Resource
    Evaluation of drug interactions in the established FEC regimen in primary cultures of tumour cells from patients (2000)
    Springer
    Annals of oncology 11 (2000), S. 1301-1307 
    Details
    ISSN: 1569-8041
    Keywords: chemotherapy ; drug interaction ; in vitroassay
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: Chemotherapy using multi-drug regimens is consideredmore active than single-agent therapy. This may be due to synergisticinteractions or, simply, a higher probability of administering an activeagent. We investigated in vitrothe type of drug interactions in arecognized regimen in relationship to tumour type and drug sensitivity. Patients and methods: The possibility of synergistic and additiveinteractions between individual cytotoxic drugs was investigated for thecomponent drugs of the established FEC regimen, i.e., 5-fluorouracil,epirubicin and cyclophosphamide, in 243 patient tumour samples representingvarious drug sensitivity using the non-clonogenic fluorometric microculturecytotoxicity assay. Results: Using a cell survival of ≤50% as a limit fordrug activity and sample sensitivity, the overall response rates to the mostactive single drug (Dmax) and the combination were 56% and64%, respectively, with a distribution among diagnoses similar to thatin the clinic. For 86% of the samples there was concordance withrespect to judgement of activity using either Dmax or thecombination. For samples being sensitive to at least one single drug,95% were also sensitive to the combination whereas for samples withinsignificant Dmax effect, only 2% were sensitive to thecombination. In samples with modest Dmax effects, i.e., cellsurvival in the range 〉50%–≤80%, 45%responded to the combination. The effect of the combination was generally wellpredicted from the Dmax effect. Conclusions:The superior antitumour effect of drug combinationscompared with single drugs may be due to the higher chance of selecting anactive agent. However, for intermediately sensitive tumours, additionalinteraction effects of a combination may be of clinical significance.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008332816407
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  • 69
    Electronic Resource
    Electronic Resource
    A phase I study of gemcitabine and epirubicin for the treatment of platinum-resistant or refractory advanced ovarian cancer (2000)
    Springer
    Annals of oncology 11 (2000), S. 613-616 
    Details
    ISSN: 1569-8041
    Keywords: chemotherapy ; ovarian cancer ; second-line
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background:Gemcitabine is active in patients with otherwiseresistant or refractory ovarian cancer. As the drug is well tolerated, studiesusing gemcitabine combined with other antineoplastic agents are needed. Theaim of the study was to determine the maximum tolerated dose (MTD) ofepirubicin combined with gemcitabine, with and without support of G-CSF. Patients and methods:Patients with platinum-resistant orrefractory ovarian cancer were eligible. Gemcitabine (G) (starting dose 800mg/m2 day 1 and 8; 200 mg/m2 escalation per level) andepirubicin (E) (starting dose 60 mg/m2 day 1; 15 mg/m2escalation per level) were given every 21 days for four to six cycles. G-CSF(filgrastim 5 µg/kg/die) was given in case of grade 4 neutropenia(levels without support) or from day 9 up to leukocyte count〉10,000/mm3 after nadir (levels with support). Cohorts of threepatients were enrolled at each level, and another three patients were planned,if one dose-limiting toxicity (DLT) was registered. MTD was determined firstwithout and then with G-CSF. Results:Four levels were studied (G 800 + E 60; G 1000 + E 60;G 1000 + E 75; G 1000 + E 75 + G-CSF) with four, four, three and threepatients enrolled, respectively. DLT (grade 4 febrile neutropenia) wasobserved in two patients at level 3. Thus, G1000 + E 60 mg/m2 wasthe MTD without G-CSF. The addition of prophylactic G-CSF did not allow afurther increase of the dose and grade 4 thrombocytopenia was the DLT at level4. Non-hematological toxicity was mild. Grade 2 mucositis was reported in fourpatients. Among the 13 patients with measurable or evaluable disease, 3partial responses were observed for an overall response rate of 23.1%. Conclusions:The combination of gemcitabine 1000 mg/m2(day 1, 8) and epirubicin at 60 mg/m2 (day 1) is a feasibletherapy. Grade 4 neutropenia is frequent and G-CSF support is often required.With prophylactic support of G-CSF, the DLT is thrombocytopenia.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008344528791
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  • 70
    Electronic Resource
    Electronic Resource
    Primary cerebral lymphomas: Unsolved issues regarding first-line treatment, follow-up, late neurological toxicity and treatment of relapses (2000)
    Springer
    Annals of oncology 11 (2000), S. 39-44 
    Details
    ISSN: 1569-8041
    Keywords: brain tumor ; chemotherapy ; encephalopathy ; late neurological toxicity ; leucoencephalopathy ; primary cerebral lymphoma ; radiochemotherapy ; systematic follow-up
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background:Primary cerebral non-Hodgkin's lymphomas (NHL) inimmunocompetent patients (PCL) are located exclusively in the central nervoussystem, the eye, or meninges. Clinical management of these patients remainscontroversial. Patients and methods:Clinical characteristics of the patients andparameters influencing their outcome as of December 1998 were investigated andregistered in a database of 226 patients treated in the French Federation ofCancer Centers between 1980 and 1995. Results:Most PCL are diffuse large-cell NHL with a B phenotype.The incidence of PCL has been steadily increasing over the past 20 years insome but not all countries. The overall survival of primary cerebral lymphoma(PCL) patients in the published series, a median of 12–16 months and afive-year survival of 5%–20%, is poor. Several series havenow reported long-term survivals of more than 10 years and PCL may thereforebe a curable tumor in some patients. The optimal treatment of PCL is notknown. Complete resection of the tumor does not improve outcome andmultidisciplinary approaches combining chemotherapy and radiotherapy are nowcommonly used, although the superiority of combination over radiotherapy- orchemotherapy-alone has never been demonstrated in a phase III trial. Theoptimal chemotherapy regimen, the dose and even the usefulness of brainradiotherapy after chemotherapy are therefore still matters of debate.Recently, several authors have reported a relatively high incidence of lateneurological sequelae after PCL treatment. Conclusions:The optimal treatment of PCL patients remains to bedefined. Large cooperative international phase III trials are now required todefine and improve the optimal treatment of PCL and reduce its sequelae.
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    URL: http://dx.doi.org/10.1023/A:1008364612406
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  • 71
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    Electronic Resource
    Treatment of Hodgkin's disease: Results and current concepts of the German Hodgkin's Lymphoma Study Group (2000)
    Springer
    Annals of oncology 11 (2000), S. 81-85 
    Details
    ISSN: 1569-8041
    Keywords: ABVD ; BEACOPP ; chemotherapy ; clinical trials ; COPP ; dose intensification ; Hodgkin's disease ; radiotherapy ; risk factors
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background:Treatment strategies in Hodgkin's disease (HD) arechanging fundamentally over the last decades. Both radiotherapy andcombination chemotherapy are effective treatment modalities. However, theoptimal choice of treatment or combinations of treatment is still debated fordifferent prognostic groups. Patients and methods:The German Hodgkin's Lymphoma Study Group(GHSG) initiated randomized clinical trials since 1978. Over the past 20years, more than 6000 patients with HD in all stages were randomized, treatedand followed by the GHSG. Patients are now being recruited from more than 300clinical centers. Results:As a consequence of different clinical trials, it is nowthe policy of the GHSG to tailor treatment to the individual risk of patients,giving favorable patients less intensive and less toxic therapy thanunfavorable patients. The treatment for early and intermediate stage HDbecomes quite similar with few cycles of polychemotherapy followed by involvedfield irradiation. In advanced stage HD, the introduction of dose intensifiedchemotherapy (BEACOPP), has improved treatment results and thus willsubstitute the MOPP or ABVD regimens. Conclusions:Although most of the patients with HD will be curedby modern treatment stategies, several questions are still subjects of ongoingclinical trials: 1) which chemotherapy regimen in which quantity will be thebest with respect to efficacy and toxicity and 2) which dose and field sizeof radiotherapy is adequate within the combined modality.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008317426152
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  • 72
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    Phase II study of the multitargeted antifolate LY231514 (ALIMTA™, MTA, pemetrexed disodium) in patients with advanced pancreatic cancer (2000)
    Springer
    Annals of oncology 11 (2000), S. 101-103 
    Details
    ISSN: 1569-8041
    Keywords: antifolate ; chemotherapy ; pancreatic cancer ; thymidylate synthase inhibitor
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Purpose:To determine the safety and activity of LY231514(ALIMTA™, MTA, pemetrexed disodium, Eli Lilly and Co.,Indianapolis, IN) in chemotherapy-naïve patients with advanced pancreaticcancer. Patients and methods:Patients with unresectable or metastaticpancreatic cancer received LY231514 600 mg/m2 as a 10–minuteinfusion every three weeks. Results:Forty-two patients were enrolled in this phase II trial.The median age was 60.3 (range 37–77) years; 79% had metastaticdisease. Neutropenia was common (40% of patients ≥ grade 3) butinfectious complications were rare. Significant anemia or thrombocytopeniaoccurred in 〈20% of patients. Non-hematologic toxicities includedgrade 2 or 3 skin reaction which was ameliorated by dexamethasone. Elevationsof bilirubin or transaminases were infrequent (〈25% of patients) anddid not require dose reductions or treatment delays. Thirty-five patientsreceived two cycles of therapy and were evaluable for response. One complete(duration 16.2 months) and one partial (duration 6.9 months) were observedresulting in an objective response rate of 5.7% for evaluable patients.In addition, 17 patients (40%) had stable disease that lasted ≥6months in 5 patients. The median survival was 6.5 months, with 28% ofpatients alive at one year. Conclusions:LY231514 is a well-tolerated agent with minimalobjective antitumor activity in pancreatic cancer. The median and one yearsurvival times, which may be important indicators in phase II trials of newagents, are of interest. Combination trials of LY231514 in pancreatic cancerare planned.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008305205159
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  • 73
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    A phase II trial of gemcitabine in combination with 5-fluorouracil (24-hour) and folinic acid in patients with chemonaive advanced pancreatic cancer (2000)
    Springer
    Annals of oncology 11 (2000), S. 1267-1272 
    Details
    ISSN: 1569-8041
    Keywords: chemotherapy ; 5-FU ; folinic acid ; gemcitabine ; Gemzar® ; pancreas cancer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background:Gemcitabine (Gemzar®) and 5-fluorouracil (5-FU)plus folinic acid (FA) both have proven activity in the treatment of patientswith advanced pancreatic cancer. The present study was initiated toinvestigate the efficacy of gemcitabine in combination with 5-FU–FA. Patients and methods:Thirty-eight patients, median age 60 years(range 34–70) with inoperable, stage IV, pancreatic cancer were enrolledinto the study and treated on an outpatient basis. All except one patientreceived at least one cycle of treatment with gemcitabine (1000mg/m2), followed by FA (200 mg/m2) and 5-FU (750mg/m2) administered as a 24-hour continuous infusion on days 1, 8,15 and 22 of a 42-day schedule. No patient had received prior chemotherapy orradiotherapy. All 38 patients were assessed for efficacy, toxicity and timeto progressive disease. Results:Two patients (5%), achieved a partial response andthirty-four patients (89%) achieved stable disease. There were twoearly deaths (≤4 weeks). The median time to progression was 7.1 months(range 0.4–18.1+; 95% confidence interval (95% CI):5.3–7.9 months). Three patients had a progression-free interval ofgreater than 12 months and 12 of 38 patients (32%) survived longer than12 months. The median overall survival was 9.3 months (range 0.5–26.5;95% CI: 7.3–13.0 months). The incidence of grade 3 and 4toxicities was low. Conclusions:The combination of gemcitabine and 5-FU–FA isactive and well tolerated and seems to offer an improvement inprogression-free interval over both gemcitabine monotherapy and 5-FU–FAtherapy.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008364018881
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  • 74
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    Hepatic arterial 5-fluorouracil in patients with liver metastases of colorectal cancer: Single-centre experience in 145 patients (2000)
    Springer
    Annals of oncology 11 (2000), S. 1563-1570 
    Details
    ISSN: 1569-8041
    Keywords: 5-fluorouracil ; arterial access device ; chemotherapy ; colorectal cancer ; hepatic arterial chemotherapy ; liver metastases ; port-a-cath
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background:Hepatic arterial chemotherapy for liver metastases ofcolorectal cancer is still under discussion. Mainly because of the technicalcomplications of this mode of treatment and the lack of a survival benefit inrandomized studies. We performed an analysis of hepatic arterial5-fluorouracil (5-FU) chemotherapy in 145 consecutive patients treated at asingle institution. Patients and methods:One hundred forty-five patients withinoperable liver metastases from colorectal cancer were included. 5-FU, 1000mg/m2/day continuous infusion for five days every three weeks, wasdelivered in the hepatic artery by percutaneous catheter or arterial accessdevice. Results:The response rate was 34% for all patients,40% in patients with extrahepatic disease, and 15% in patientswith i.v. 5-FU-based pretreatment. TTP and OS for all patients were 7.5 and14.3 months, respectively. In patients with extrahepatic disease or i.v.5-FU-based pretreatment, OS was significantly shorter compared to patientswithout extrahepatic disease or 5-FU-based pretreatment (9.7 vs. 19.3 monthsand 10.1 vs. 17.4 months, respectively). forty-seven percent of patientsstopped treatment because of a complication. Complications most often seen inpatients with arterial ports were hepatic artery thrombosis (48%) anddislocation of the catheter (22%). Conclusions:The results of our analysis are in line with previousphase III studies. Extrahepatic disease and i.v. 5-FU-based pretreatment wereprognostic for reduced OS. The complication rate of hepatic arterial deliverywas worrisome, although, no negative impact on survival could be established.There is a strong need for improvement of hepatic arterial delivery methodsbefore further evaluation of hepatic arterial 5-FU will be worthwhile.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008369520179
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  • 75
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    High-dose therapy with autologous stem-cell transplantation (ASCT) after first progression prolonged survival of follicular lymphoma patients included in the prospective GELF 86 protocol (2000)
    Springer
    Annals of oncology 11 (2000), S. 1585-1590 
    Details
    ISSN: 1569-8041
    Keywords: autologous stem-cell transplantation ; chemotherapy ; follicular lymphoma ; progression
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background:Among the 566 patients with follicular lymphomas (FL)included in the GELF 86 prospective trials from October 1986 to September1995, 372 with progressive/relapsing disease were analyzed retrospectively toidentify prognostic factors at first relapse. Patients and methods:For progressive FL, patients received mono-(22%) or polychemotherapy (78%) followed by high-dose therapy(HDT) with ASCT for 83 patients (22%). The median time toprogression from initial treatment was 23 months (range 3–102 months)and 24% of documented patients (52 of 217) had histologicaltransformation (HT). Salvage therapy produced an overall response in64% of patients and the five-year survival from progression was42%. Results:For patients who underwent HDT with ASCT compared tostandard treatment, five-year freedom from second failure was at 42%vs. 16% (P = 0.0001) and five-year survival was58% vs. 38% (P = 0.0005), respectively. Thebenefit of HDT and ASCT remained if we consider only patients less than 65years (five-year survival at 60% vs. 40%; P =0.001). Multivariate analysis of parameters significant according tounivariate analysis found that no ASCT at first progression, age at relapse〉50 years, progression on-therapy were adversely significant onsurvival. Conclusions:HDT with ASCT compared to standard treatmentprolonged remission and survival after first progression of FL patients.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008399623564
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  • 76
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    Cost-effectiveness of second-line treatment with irinotecan or infusional 5-fluorouracil in metastatic colorectal cancer (2000)
    Springer
    Annals of oncology 11 (2000), S. 157-161 
    Details
    ISSN: 1569-8041
    Keywords: 5-fluorouracil ; chemotherapy ; colorectal cancer ; cost/effectiveness analysis ; irinotecan
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background:It has been shown that irinotecan is superior toinfusional 5-fluorouracil (5-FU) in patients with advanced colorectal cancerafter 5-FU failure. In a recent trial, median survival was 10.8 months forpatients treated with irinotecan, compared to 8.5 months in patients receivinginfusional 5-FU. Considering the statistically significant but clinicallyrelatively small advantage of irinotecan over 5-FU, cost effectiveness shouldalso be part of treatment decision. Purpose:To relate the costs of each management approach tooverall survival in patients with metastatic colorectal cancer. Patients and methods:The healthcare costs and medical benefits(treatment-added survival) of second-line chemotherapy in patients (infusional5-FU: 129, irinotecan: 127) were compared. Data on overall survival were drawnfrom a multicenter randomised trial that compared infusional 5-FU (continuousinfusion, AIO, or LV5-FU2 regimens) to irinotecan alone. Costs were derivedfrom the accounting system in two university hospitals in Paris, France. Results:The range in total healthcare costs was 14,135 to 12,192US$ patient between management approaches, with irinotecan chemotherapycosting most and 5-FU-continuous infusion least. If survival was included asa treatment benefit, the cost-effectiveness ratio of irinotecan over 5-FUranged from 9,344 to 10,137 US$ per year of added survival. Conclusions:The least expensive management for metastaticcolorectal was 5-FU infusion but the additional cost of irinotecan wasbalanced by the added months of survival, with a cost-effectiveness ratioclose to that of other cancer treatments.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008358411251
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  • 77
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    Phase II trial of gemcitabine in patients with previously untreated metastatic cancer of the esophagus or gastroesophageal junction (2000)
    Springer
    Annals of oncology 11 (2000), S. 1161-1164 
    Details
    ISSN: 1569-8041
    Keywords: chemotherapy ; esophageal cancer ; gemcitabine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background:There were approximately 12,500 cases of esophageal carcinoma diagnosed in the US in 1992 and 12,200 deaths. The impact of chemotherapy on patients with metastatic disease is marginal with a median survival of only five months. Gemcitabine (LY188011,2,2,–difluorodeoxycytidine: dFdC), an analog of cytosine arabinoside (ara-C), is a pyrimidine antimetabolite. Gemcitabine has shown interesting clinical activity in initial phase II clinical trials in a variety of malignancies, including the aerodigestive malignancies, squamous-cell carcinoma of the head/neck and both non-small-cell and small-cell lung cancer. Patients and methods:A total of 21 patients with chemotherapy-naïve metastatic esophageal carcinoma were entered. Nineteen patients were evaluable for toxicity and seventeen patients were evaluable for response. Gemcitabine was administered intravenously at 1250 mg/m2 over 30–60 minutes on days 1, 8, and 15 followed by 1 week of rest. This four-week schedule defined a cycle of treatment. Patients may have received a maximum of six cycles. Results:Gemcitabine was well tolerated with minimal non-hematologic toxicity and grade 3–4 anemia, granulocytopenia, and thrombocytopenia occurring in 10.5%, 21%, and 0% of patients, respectively. No responses were seen in the seventeen evaluable patients. Conclusions:At the dose and schedule studied it would appear that gemcitabine has no activity in patients with chemotherapy-naïve esophageal carcinoma.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008369718242
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  • 78
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    Electronic Resource
    Vitamin C induced apoptosis in human articular chondrocytes (2000)
    Springer
    Pflügers Archiv 440 (2000), S. r046 
    Details
    ISSN: 1432-2013
    Keywords: Key words vitamin C (L-ascorbic acid) ; apoptosis ; human articular chondrocytes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Chondrocytes present in articular cartilage survive as a resident cell population throughout the lifespan of the individual organism. However, articular chondrocytes as other cells also undergo apoptosis and there is an ever increasing list of diverse stimuli that can induce this phenomenon in vitro. Our main interest was to investigate potential cytotoxic effects of vitamin C (L-ascorbic acid) on human articular chondrocytes. The present study suggests that vitamin C can induce apoptosis in a cell culture of chondrocytes after 18 h of cultivation. Apoptosis-inducing activity of L-ascorbic acid is dose dependent and significantly affected by the presence of serum. The increased number of vitamin C induced apoptotic cells was associated with DNA fragmentation and morphological changes of the cells.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004240000001
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  • 79
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    Infusional ECarboF in patients with advanced breast cancer: A very active and well-tolerated out-patient regimen (2000)
    Springer
    Annals of oncology 11 (2000), S. 1557-1561 
    Details
    ISSN: 1569-8041
    Keywords: breast cancer ; carboplatinum ; chemotherapy ; continuous 5-fluorouracil
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We performed a trial using the combination of epirubicin 50mg/m2/day 1, carboplatinum AUC 5/day 1 and continuous5-fluorouracil (5-FU) 200 mg/m2/day (every 4 weeks for6 months) to confirm the efficacy and low toxicity profile of thisregimen in breast cancer. In 51 patients with metastatic(n = 33) or locally advanced (n = 18)breast cancer the overall response rate was 86% (95% confidenceinterval (95% CI): 73%–94%): 94% in locallyadvanced and 81% metastatic disease. Grade 3–4 toxicity was low:4% of patients presented with febrile neutropenia, 16% withsevere palmar-plantar syndrome, 10% with Port-a-cath thrombosis. This study confirms the high efficacy of infusional 5-FU-based regimens andjustifies further research into novel promising oral 5-FU derivatives.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008378220547
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  • 80
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    Electronic Resource
    Intra-arterial chemotherapy for unresectable pancreatic cancer (2000)
    Springer
    Annals of oncology 11 (2000), S. 569-573 
    Details
    ISSN: 1569-8041
    Keywords: chemotherapy ; intra-arterial ; liver metastasis ; unresectable pancreatic cancer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background:A phase II trial of a new intra-arterial chemotherapyregimen for unresectable pancreatic cancer (UPC). Patients and methods:Ninety-six patients with UPC were treatedwith intra-arterial chemotherapy at three-weekly intervals. The schedule usedwas FLEC: 5-fluorouracil 1000 mg/m2, folinic acid 100mg/m2, carboplatin 300 mg/m2; epirubicin 60mg/m2. Results:The overall response rates by CT-scan evaluation were:15% partial response (PR), 44% stable disease (SD), 17%progressive disease (PD). The overall median survival was 9.9 months, and 10.6and 6.8 for UICC stage III and IV, respectively. Pain reduction occurred in42% of patients. A weight gain 〉7% from baseline occurred in8% of patients. A total of 341 courses of FLEC were administered. Grade3–4 hematological toxicity was seen in 25% of patients;ematemesis in 4%; grade 3 gastrointestinal toxicity in 3%; andgrade 3 alopecia in 16%. One sudden death, a pre-infarction angina, anda transitory ischemic attack were observed. The only complication related tothe angiographic procedure was an intimal dissection of the iliac artery. Conclusions:The intra-arterial FLEC regimen was well toleratedand active. It requires only one day of hospitalization. Efficacy could onlybe assessed in a randomized study against a gemcitabine containing regimen.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008335331516
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  • 81
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    Ifosfamide plus oral etoposide salvage chemotherapy for platinum-resistant paclitaxel-pretreated ovarian cancer (2000)
    Springer
    Annals of oncology 11 (2000), S. 607-612 
    Details
    ISSN: 1569-8041
    Keywords: chemotherapy ; combination ; etoposide ; ifosfamide ; ovarian cancer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background:The prognosis of platinum resistant ovarian cancer isvery poor and the treatment of choice has not been clearly defined. Patients and methods:We conducted a phase II study with thecombination of ifosfamide i.v. at 2.25 g/m2 (days 1, 2) andetoposide per os at 100 mg daily (days 1–10) every four weeks. To beeligible for the study patients had to be resistant to platinum and paclitaxelpretreated. Results:Forty-one patients entered the study. The median intervalfrom the previous chemotherapy was 3.9 months. The median number of previouschemotherapeutic regimens was 2. Severe toxicities included neutropenia(41% of patients), leukopenia (29%) and thrombocytopenia(13%). Thirty-five patients are assessable for response. Nine patientsresponded (22% of the eligible, 26% of the assessable), four ofthemdemonstrated complete response to chemotherapy (10% and 12%,respectively), while three patients demonstrated stabilization of theirprogressive disease. After a median follow-up of 18 months, time toprogression is 3 months (range 0.9–14.4), duration of response is 9months (2.5–11) and median survival is 13 months (2.5–37.4+). Conclusions:The combination of ifosfamide with oral etoposideappears to have significant but manageable toxicity and encouraging efficacyin platinum resistant ovarian cancer.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008327412571
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  • 82
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    Recurrent squamous-cell carcinoma of the head and neck: Overview of current therapy and future prospects (2000)
    Springer
    Annals of oncology 11 (2000), S. 11-16 
    Details
    ISSN: 1569-8041
    Keywords: chemotherapy ; gene therapy ; head and neck cancer ; immunotherapy ; radiotherapy ; recurrent ; surgery
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Locoregional recurrence is the most common cause of failure after head andneck cancer surgery. It is a disease which causes significant morbidityespecially on speech and swallowing. There are many different treatmentsavailable including surgery, reirradiation and chemotherapy. However, none ofthese have produced any significant survival benefit. Because of this, therehas been considerable interest in the development of new biological therapiessuch as gene therapy and immunotherapy for this disease. The objectives ofthis article are to provide an overview of the currently available therapiesfor recurrent head and neck cancer including gene therapy and immunotherapy.Prevention of recurrent disease by the detection and treatment of minimalresidual disease is also discussed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008330026617
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  • 83
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    A phase II study of pegylated liposomal doxorubicin for treatment of advanced hepatocellular carcinoma (2000)
    Springer
    Annals of oncology 11 (2000), S. 113-114 
    Details
    ISSN: 1569-8041
    Keywords: chemotherapy ; hepatocellular carcinoma ; liposomal doxorubicin ; phase II
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background:Pegylated liposomal doxorubicin has an enhancedefficacy and reduced toxicity compared with free doxorubicin. The efficacy andtoxicity of pegylated liposomal doxorubicin was investigated in patients withhepatocellular carcinoma. Patients and methods:Patients with histologically confirmed,locally advanced or metastatic hepatocellular carcinoma and a Karnofsky index〉60% were included in this prospective single-arm study. Exclusioncriteria were liver cirrhosis stage Child–Pugh C, previous chemotherapy,or chemoembolization. Pegylated liposomal doxorubicin was given in a dose of30 mg/m2 every three weeks until progression of disease. Afterinclusion of five patients the dose could be escalated to 40 mg/m2in absence of toxicity grade 3 and 4. Results:Sixteen patients were evaluable for response. Noobjective response was achieved. The median survival time was 140 days(95% confidence interval: 126–154 days). Treatment toxicitiesgrade ≥3 comprised increased liver enzymes in patients with preexistinggrade 1 or 2 elevation (n = 6), hematologic toxicity (n =5), and hypersensitivity (n = 2). Conclusions:Pegylated liposomal doxorubicin is not effective fortreatment of advanced hepatocellular carcinoma. The favorable toxicity profilewas confirmed even in patients with underlying liver disease.
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    URL: http://dx.doi.org/10.1023/A:1008386822906
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  • 84
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    Electronic Resource
    A phase I–II study of gemcitabine and paclitaxel in advanced non-small-cell lung cancer patients (2000)
    Springer
    Annals of oncology 11 (2000), S. 109-112 
    Details
    ISSN: 1569-8041
    Keywords: chemotherapy ; gemcitabine ; non-small-cell lung cancer ; paclitaxel
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Thirty patients with chemotherapy-naïve advanced non-small-cell lungcancer (NSCLC) were given escalating doses of paclitaxel (150, 175, 200mg/m2) on day 1 in three consecutive cycles, together with a fixeddose of gemcitabine 1000 mg/m2 on days 1 and 8; cycles wererepeated every three weeks. The dose escalation of paclitaxel was feasible inthe majority of patients. Subsequently, 30 other NSCLC patients received adose of 200 mg/m2 paclitaxel with gemcitabine 1000 mg/m2in a phase II study. The major side effect was mild myelosuppression. Aresponse rate of 24% was achieved in 49 fully evaluable patients. Thisregimen proved to be safe and easy to administer on an out-patient setting,and constitutes now one of the arms of the current EORTC randomized study foradvanced NSCLC.
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    URL: http://dx.doi.org/10.1023/A:1008321000887
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  • 85
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    Acute hematologic toxicity and practicability of dose-intensified BEACOPP chemotherapy for advanced stage Hodgkin's disease (2000)
    Springer
    Annals of oncology 11 (2000), S. 1105-1114 
    Details
    ISSN: 1569-8041
    Keywords: BEACOPP ; chemotherapy ; dose intensification ; hematotoxicity ; Hodgkin's disease ; practicability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background:Evidence is recently accumulating that the novelBEACOPP (bleomycin (B), etoposide (E), adriamycin (A), cyclophosphamide (C),vincristine (O), procarbazine (P), prednisone (P)) chemotherapy is a highlyeffective treatment for advanced stage Hodgkin's disease. Two dose variantsof BEACOPP are currently tested in a phase III randomized multicenter trialof the GHSG. To enable more extensive testing of BEACOPP we characterized itspracticability regarding schedule adherence, acute hematotoxicity and need forsupportive treatment. Patients and methods:Data of 858 patients (6592 therapy cycles)from 184 participating institutions were evaluated. Planned total drug dosesof the baseline variant (arm 1) were 80, 2400, 200, 5200, 11.2, 5600 and 4480mg/m2 for B, E, A, C, O, P and P, respectively. Compared to arm 1,the doses of E, A and C in the dose-intensified variant (arm 2) were escalatedby factor 2.0, 1.4, 1.92, respectively, using G-CSF assistance. Stepwise dosereductions were specified in case of dose-limiting toxicities. Both variantsare given in eight three-weekly courses. Results:Median dose adherence (dose actually given relative toplanned arm 1 dose) in arm 1 was 1.0 for all drugs. Relative dose escalationof E, A, and C actually maintained in arm 2 was 1.83, 1.37 and 1.77 (medians),respectively, and 70% of patients maintained elevated dose levelsthroughout the entire treatment. Dose-limiting toxicities occurred in25% of cycles in arm 2, most frequently due to leukocytopenia andthrombocytopenia. Time courses of leukocytes in arm 2 showed more severe butnot more prolonged leukocytopenia compared with arm 1. WHO grades 3–4infections were documented in 2.1% (arm 1) and 3.1% (arm 2) ofall cycles. Erythrocytes were transfused in 6% (arm 1) and 28%(arm 2), platelets in 〈1% (arm 1) and 6% (arm 2) of allcycles. Conclusions:Both BEACOPP schemes are practicable in a largemulticenter setting. Despite increased hematotoxicity, moderate doseescalation is safe for the majority of the patients with G-CSF assistance andstandard supportive treatment.
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    URL: http://dx.doi.org/10.1023/A:1008301225839
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  • 86
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    Radiation myositis: The possible role of gemcitabine (2000)
    Springer
    Annals of oncology 11 (2000), S. 1615-1616 
    Details
    ISSN: 1569-8041
    Keywords: chemotherapy ; gemcitabine ; radiotherapy ; radiation myositis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008353224251
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  • 87
    Electronic Resource
    Electronic Resource
    A phase II trial of docetaxel in platinum pre-treated patients with advanced epithelial ovarian cancer: A Japanese Cooperative Study (2000)
    Springer
    Annals of oncology 11 (2000), S. 1531-1537 
    Details
    ISSN: 1569-8041
    Keywords: advanced ovarian cancer ; chemotherapy ; docetaxel ; phase II trial
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background:This phase II study was conducted to evaluate theefficacy and toxicity of docetaxel in Japanese patients with advanced ovariancancer. Patients and methods:Docetaxel was administered at a dose of 70mg/m2 intravenously to patients with platinum pre-treated advancedovarian cancer. Treatment was repeated every three weeks. No routinecorticosteroid premedication was given. Results:Ninety patients with advanced ovarian cancer were enteredand sixty were assessable for response. The overall response rate was28% in the assessable patients (95% confidence interval(95% CI): 17.5%–41.4%). CA125 responses were seenin 8 (24%) of 34 assessable patients for CA125 criteria. The 36platinum-refractory patients had a response rate of 25% compared with33% in the platinum-sensitive patients. The predominant toxicity wasneutropenia, with 86% of the patients experiencing grade 3 or 4.Hypersensitivity reactions occurred in 37% of the patients and were notlife threatening. Edema was mild and infrequent. Conclusion:Docetaxel at 70 mg/m2 demonstratedeffectiveness as a treatment of both platinum-sensitive andplatinum-refractory ovarian cancer patients, with a low incidence of severehypersensitivity reactions and edema.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008337103708
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  • 88
    Electronic Resource
    Electronic Resource
    Is `one cycle every three or four weeks' obsolete? A critical review of dose-dense chemotherapy in solid neoplasms (2000)
    Springer
    Annals of oncology 11 (2000), S. 133-149 
    Details
    ISSN: 1569-8041
    Keywords: chemotherapy ; dose ; dose-density ; dose-intensity ; high-dose chemotherapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background:Shortening the interval between cycles is one meansof increasing the dose intensity of chemotherapy, and can be supported bybiological and mathematical rationales. Our objective was to assess theclinical relevance of the rapid repetition of regimens (so-called `dose-densechemotherapy') in various solid neoplasms. Design:The medical literature was reviewed in accord withMulrow's recommendations. Randomised studies comparing frequently-repeatedchemotherapy to standard regimens as well as open studies are described andcritically examined. Results:Dose-dense regimens were widely found to be feasible. In small-cell lung cancer, survival of patients receiving dose-denseregimens was better than that of patients treated by standard chemotherapy inthree trials, two of which reached significance, when these intensive regimensallowed better dose intensity. In poor-prognosis germ-cell tumors, a dose-dense regimen was not betterthan standard therapy, perhaps because of an excessively high toxicity-relateddeath rate. However, recent phase II studies have provided encouragingresults. In early breast cancer, the one published randomized study in the adjuvantsetting showed only a trend towards better disease-free survival innode-positive women receiving a weekly-repeated regimen. Two randomized trialsfailed to show any benefit in the neoadjuvant setting with a dose-denseregimen. No evidence of a benefit was provided in metastatic breast cancer. In advanced colorectal cancer, evidence of an improvement in survival withweekly or bi-weekly 5-FU–leucovorin compared to a classic monthlyschedule has recently been shown in two randomized trials, and dose-denseregimens are recognized as standard therapy in many countries. Phase II studies of dose-dense regimens have also shown high response ratesand long survival in many neoplasms, including Ewing's sarcoma, gestationaltrophoblastic disease, ovarian carcinoma and gastric cancer. Conclusions:A considerable amount of experience has been gainedwith frequently-repeated regimens. A few randomized trials have demonstrateda benefit for survival on standard chemotherapy in small-cell lung cancer andadvanced colorectal cancer. However, this benefit appears to be weak. Thecombination of dose-dense chemotherapy regimens with new anti-cancerstrategies based on our insights into the mechanisms of oncogenesis is achallenge on the eve of the millennium.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008344014518
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  • 89
    Electronic Resource
    Electronic Resource
    Thyroid carcinosarcoma, a rare and aggressive histotype: A case report (2000)
    Springer
    Annals of oncology 11 (2000), S. 1497-1499 
    Details
    ISSN: 1569-8041
    Keywords: carcinosarcoma ; chemotherapy ; thyroid
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Thyroid carcinosarcoma is a rare and aggressive thyroid tumor. Histologicalexamination of a tumor showed the characteristic of epithelial carcinoma andmesenchymal differentiation. We retrospectively analyzed the course of thepatient and reviewed the literature in which only 19 other cases aredescribed. Carcinosarcoma of the thyroid is a very aggressive tumor with aclinical course similar to anaplastic thyroid carcinoma. Survival is veryshort despite aggressive multimodal treatment.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1026538410510
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  • 90
    Electronic Resource
    Electronic Resource
    Acute myeloid leukemia and lung cancer occurring in a chronic lymphocytic leukemia patient treated with fludarabine and autologous peripheral blood stem-cell transplantation (2000)
    Springer
    Annals of oncology 11 (2000), S. 1493-1495 
    Details
    ISSN: 1569-8041
    Keywords: acute myeloid leukemia ; chemotherapy ; chronic lymphocytic leukemia ; immunosuppression ; second neoplasms
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract An increased incidence of different malignancies associated to chroniclymphocytic leukemia (CLL) has been reported. The association of CLL and acuteleukemia is a rare event described in 〈1% of CLL, the type of acuteleukemia being either from the lymphoid or more often from the myeloidlineage. The coexistence of acute myeloid leukemia (AML) and CLL in the samepatient has been occasionally reported. Most of these cases have beenassociated with the administration of chemotherapy or radioterapy for CLL,suggesting that the former may be a secondary leukemia. On the other hand, CLLcould precede, but could also be diagnosed at the same, or delayed time asAML, suggesting the presence of other leukemogenic factors. We describe theexceptional development of AML and lung cancer in a patient with previouslydiagnosed CLL in minimal residual disease status after fludarabine treatmentfollowed by autologous peripheral blood stem-cell transplantation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1026505632679
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  • 91
    Electronic Resource
    Electronic Resource
    Phase II EORTC trial with 5-fluorouracil, cisplatin and interferon-α as second-line treatment of advanced transitional cell cancer of the urothelial tract (2000)
    Springer
    Annals of oncology 11 (2000), S. 1391-1394 
    Details
    ISSN: 1569-8041
    Keywords: chemotherapy ; interferon ; transitionall-cell carcinoma ; urothelial tract
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background:Based on the favorable results of the combination5-fluorouracil (5-FU), cisplatin and interferon-α as second-line treatmentin advanced metastatic transitional-cell carcinoma of the urothelial tract aconfirmatory study was executed in a multicenter setting. Patients and methods:In this open label phase II study 43patients failing adequate previous chemotherapy were treated with IFN-α2b5 MU/m2 subcutaneously for 5 consecutive days starting on day 1 and22 simultaneous with 5-FU 500 mg/m2 daily as a continuous infusion.In between the same dose of IFN-α2b was given 3 times weekly with CDDP 25mg/m2 on days 1, 8, 15 and 22. This cycle was repeated every sixweeks. Results:In 40 eligible patients 5 PR were seen (12.5%;95% confidence interval (95% CI):4.1%–26.8%). The major toxicity was hematological. Twotoxic deaths were seen due to gastro-intestinal hemorrhage. Conclusions:In view of these results this combination can not berecommended as second line treatment for metastatic transitional-cellcarcinoma of the urothelial tract.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1026589120989
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  • 92
    Electronic Resource
    Electronic Resource
    Metastatic secretory breast cancer. Non-responsiveness to chemotherapy: Case report and review of the literature (2000)
    Springer
    Annals of oncology 11 (2000), S. 1343-1347 
    Details
    ISSN: 1569-8041
    Keywords: chemotherapy ; Her2/neu ; indolent ; malignant ; palliative care ; secretory breast cancer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Secretory carcinoma of the breast is a rare and indolent tumour originallydescribed in children but occurring equally in the adult population. Theprincipal management problems following primary surgical treatment are localrecurrence and axillary lymph node metastases. Distant metastases areextremely rare. We present the case of a 27-year-old woman with pulmonary metastases froma secretory breast cancer treated by mastectomy and axillary lymph nodedissection 12 years previously. There was no response to chemotherapy; however, the patient remained aliveand active two years from presentation with metastatic disease and one yearfrom cessation of all cytotoxic chemotherapy. She eventually died ofrespiratory failure two and a half years after presentation. To our knowledge, this is only the fourth reported case of distantmetastases from secretory breast cancer and the second reported case in whichcurrent active chemotherapy has been used. We review the literature anddiscuss the apparent chemoresistance of this tumour including the lack ofmembrane staining for Her2/neu. In the absence of any proven effective chemotherapy we believe that symptomcontrol becomes the focus of management and offers patients with metastaticsecretory breast cancer the greatest chance of a functional and good qualityexistence.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008387800525
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  • 93
    Electronic Resource
    Electronic Resource
    Downstream molecular determinants of response to 5-fluorouracil and antifolate thymidylate synthase inhibitors (2000)
    Springer
    Annals of oncology 11 (2000), S. 385-391 
    Details
    ISSN: 1569-8041
    Keywords: 5-fluorouracil ; antifolates ; apoptosis ; DNA repair ; p53 ; thymidylate synthase
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Thymidylate synthase (TS) is an essential enzyme for the de novo synthesis of thymidylate and subsequently DNA synthesis. TS has been usedas a target for cancer chemotherapy in the development of fluoropyrimidinessuch as 5-fluorouracil (5-FU) and 5-fluorodeoxyuridine and of novelfolate-based TS inhibitors such as ZD1694 (Tomudex, Raltitrexed), ZD9331,LY231514 (ALIMTA, Pemetrexed), AG337 (Thymitaq, Nolatrexed) and AG331.Although TS has been considered as a target for chemotherapy, the precisemechanism by which TS inhibition leads to cell death is still not completelyresolved. TS inhibition results in depletion of dTTP, an essential precursorfor DNA, and an increase in dUTP. This results in the so-called thymine-lessdeath due to misincorporation of dUTP into DNA; its excision, catalysed byuracil-DNA glycosylase, results in DNA damage. Both this imbalance indTTP/dUTP and DNA damage can result in induction of downstream events, leadingto apoptosis. On the other hand a specific interaction exists betweenoncogenes and TS, by binding of TS protein to the p53and c-mycRNA, while wt p53can also inhibit TS promotor activity. TSinhibition by either 5-FU or antifolates can also result in a depression ofTS protein mediated inhibition of TS mRNA translation leading to induction ofmore TS protein synthesis, and p53protein may further deregulatethis process. These complex indirect and direct interactions between oncogenesand TS may have as yet unclear clinical implications, since most data arebased on in vitroor in vivo studies and some results arecontradictive. In some preliminary clinical studies evidence was postulatedfor a combined prognostic role for TS and p53.This knowledge shouldbe used to design clinical studies with the aim to deliver effective treatmentto potentially sensitive patients both in the adjuvant setting and in advancedstage disease.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008351221345
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  • 94
    Electronic Resource
    Electronic Resource
    A phase I trial of docetaxel and gemcitabine in patients with advanced cancer (2000)
    Springer
    Annals of oncology 11 (2000), S. 421-426 
    Details
    ISSN: 1569-8041
    Keywords: chemotherapy ; docetaxel ; gemcitabine ; non-small-cell lung cancer ; phase I trials ; taxanes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background:Docetaxel and gemcitabine are active in a broad rangeof malignancies. The objective of this phase I trial was to determine themaximally tolerated doses of the combination of docetaxel and gemcitabine. Patients and methods:Patients with advanced cancer, WHOperformance status 0–2, who had received up to one prior chemotherapyregimen were treated with gemcitabine on days 1 and 8 and docetaxel on day 8repeated every 21 days. Prophylactic ciprofloxacin was commenced on day 11 ofeach cycle and continued until the neutrophil count reached 1.0 ×109/l. G-CSF was not administered. Dose levels studied weredocetaxel/gemcitabine: 60/800, 60/1000, 75/1000, 75/1200, 85/1200 and 100/1200mg/m2. Results:Thirty-nine patients were entered and all were assessablefor toxicity. The highest administered dose level was 100 mg/m2docetaxel and 1200 mg/m2 gemcitabine with dose limiting toxicitiesof febrile neutropenia, grade 4 neutropenia ≥7 days, grade 4thrombocytopenia, grade 3 stomatitis and/or grade 3 fatigue in three out ofsix patients. Treatment was well tolerated (40 cycles) in the 10 patientstreated at the recommended dose level (85/1200) with only a single episode offebrile neutropenia and grade 3 or 4 non-hematologic toxicity was infrequent.There was no significant pulmonary toxicity. Responses were seen in a rangeof malignancies including non-small-cell lung cancer. Conclusions:The recommended dose level of 85 mg/m2docetaxel and 1200 mg/m2 gemcitabine has a favourable toxicityprofile and is suitable for further investigation in phase II trials. Thisnon-platinum containing regimen warrants further investigation as a potentialalternative to platinum containing regimens in non-small-cell lung cancer andother malignancies.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008384326701
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  • 95
    Electronic Resource
    Electronic Resource
    Phase I study with weekly cisplatin–paclitaxel and concurrent radiotherapy in patients with carcinoma of the cervix uteri (2000)
    Springer
    Annals of oncology 11 (2000), S. 455-459 
    Details
    ISSN: 1569-8041
    Keywords: cervical cancer ; chemotherapy ; phase I ; radiotherapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background.Cisplatin and paclitaxel are active in cervical cancerand both are able to potentiate the effects of radiotherapy. In this study weevaluated the maximum-tolerated dose (MTD) of paclitaxel in combination witha fixed dose of cisplatin when given weekly concurrently with pelvicradiotherapy to patients with carcinoma of the cervix uteri. Patients and methods:Eighteen patients with cervical cancer wereenrolled in this study. Cisplatin (30 mg/m2) and paclitaxel(starting dose 40 mg/m2; 5 mg/m2 escalation per level)were given on day 1 of radiotherapy and then weekly for six times.Radiotherapy was given to the pelvis with a four-field box technique for fivedays each week. Patients received 65 Gy in 1.8 Gy fractions. Cohorts of threepatients were enrolled at each level and three further patients were includedif one or two dose-limiting severe adverse events (SAE) were recorded. SAE wasdefined as grade 3 or 4 nonhematologic toxicity, excluding nausea or vomitingand alopecia, grade 4 neutropenia or thrombocytopenia, and prolonged (〉1week) neutropenia or thrombocytopenia. Results:Four levels were studied (paclitaxel 40, 45, 50, 55mg/m2) with three, five, four and six patients enrolled,respectively. The MTD of paclitaxel was found at 50 mg/m2/wk andcisplatin 30 mg/m2/wk. Diarrhea was the dose-limiting toxicity.Thirteen patients were evaluable for response: seven complete and five partialresponses were obtained with an overall response rate of 92.3%. Conclusions:The MTD of paclitaxel is 50 mg/m2/wk whenassociated to cisplatin 30 mg/m2/wk and concurrent pelvicradiotherapy. Diarrhea is the dose limiting side effect. Preliminary datasuggest that concurrent chemoradiotherapy with paclitaxel and cisplatin couldbe a very active treatment for patients with locally advanced carcinoma of thecervix.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008379922120
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  • 96
    Electronic Resource
    Electronic Resource
    Grading of chemotherapy-induced peripheral neuropathy (2000)
    Springer
    Annals of oncology 11 (2000), S. 509-513 
    Details
    ISSN: 1569-8041
    Keywords: assessment ; chemotherapy ; eripheral neuropathy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008345613594
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  • 97
    Electronic Resource
    Electronic Resource
    Gemcitabine and vinorelbine as second-line treatment in patients with metastatic breast cancer progressing after first-line taxane-based chemotherapy: A phase II study conducted by the Hellenic Cooperative Oncology Group (2000)
    Springer
    Annals of oncology 11 (2000), S. 873-875 
    Details
    ISSN: 1569-8041
    Keywords: advanced breast cancer ; chemotherapy ; gemcitabine ; vinorelbine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background:Gemcitabine and vinorelbine have shown activity inbreast cancer. A phase II trial was initiated in order to evaluate theresponse rate (RR) and time to progression (TTP) of the combination of the twodrugs in patients with metastatic breast cancer progressing after first-linetaxane-based chemotherapy. Patients and methods:Thirty-one patients were treated with thecombination of gemcitabine 1000 mg/m2 days 1 + 8 and vinorelbine30 mg/m2 days 1 + 8. The cycles were repeated every three weeks. Results:Of 27 evaluable patients 1 (4%, 95%confidence interval (95% CI): 0.1%–19%) achievedcomplete remission (CR), five (18%; 95% CI:6%–38%) partial remission (PR), eleven (40%;95% CI: 22%–61%) stable disease and ten patientsprogressed. The median duration of response was six months (range 4–10+)and the median duration of disease stabilization was five months (range2–22+). With a median follow-up of 16 months (range 0.4–22+) themedian TTP was 3.5 months (range 0.4–22+) and the median survival was9.5 months (range 0.4–22+). Grade 3–4 toxicities weregranulocytopenia 15 patients (48%), rash 3 patients (10%),neuropathy 1 patient (3%) and thrombocytopenia 1 patient (3%).In conclusion the combination of gemcitabine/vinorelbine in the dosesadministered in this group of patients had a response rate of 22% andneeds to be further evaluated in metastatic breast cancer.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008361711049
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  • 98
    Electronic Resource
    Electronic Resource
    Therapeutic management of primary central nervous system lymphoma: Lessons from prospective trials (2000)
    Springer
    Annals of oncology 11 (2000), S. 927-937 
    Details
    ISSN: 1569-8041
    Keywords: brain lymphomas ; chemotherapy ; intrathecal chemotherapy ; methotrexate ; primary central nervous system lymphoma ; radiotherapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Primary central nervous system lymphomas (PCNSL) are aggressivemalignancies, exhibiting one of the worst prognoses among lymphomas. The besttreatment modality for PCNSL has not yet been identified. Several therapeuticquestions still remain unanswered, and some methodological pitfalls inclinical trials prevent definitive conclusions from being drawn. In thisreview, certain aspects of trial design as well as emerging therapeuticguidelines are analyzed, and future perspectives are discussed. In the vast majority of prospective trials, general criteria for treatmentof aggressive lymphomas were adopted, choosing primary chemotherapy (CHT)followed by radiotherapy (RT) as therapeutic modality. This strategy produceda five-year survival of 22%–40% in comparison to the3%–26% reported with RT alone. Systemic high-dosemethotrexate (HD-MTX) seems to be the most effective drug, producing aresponse rate of 80%–90% and a two-year survival of60%–65%. To date, the addition of other drugs atconventional doses have not consistently improved outcome. With a fewexceptions, any regimen without HD-MTX comprehensively performed no betterthan RT alone. In combined treatment, RT doses should be decided on the bases of responseto primary CHT and the number of lesions, and, until definitive conclusionsfrom well-designed trials are available, RT parameters should follow thewidely accepted principles used for other aggressive lymphomas. CHT asexclusive treatment, keeping RT for relapses or persistent disease, appearsto be an attractive strategy. However, the worldwide experience with thismodality is still limited, and corroborating data are needed. Intrathecal CHTstill has not found a defined role in PCNSL management. Preliminary data seemto indicate that adequate meningeal treatment with HD-MTX, but withoutintrathecal CHT, could also be suitable in positive-cerebrospinal fluidpatients. Future efforts should be addressed to identify new active drugs and moreefficient CHT combinations, to evaluate the efficacy of high-dose CHTsupported by autologous peripheral blood stem cells transplantation, and toclarify the impact of RT delay in complete responders, the usefulness ofintrathecal CHT, and the best management for elderly patients. The assessmentof impact of treatment on neuropsychological functions and quality of life isa mandatory endpoint in clinical trials.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008376412784
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  • 99
    Electronic Resource
    Electronic Resource
    Acute deterioration of Charcot–Marie–Tooth disease IA (CMT IA) following 2 mg of vincristine chemotherapy (2000)
    Springer
    Annals of oncology 11 (2000), S. 743-747 
    Details
    ISSN: 1569-8041
    Keywords: Charcot–Marie–Tooth disease ; chemotherapy ; hereditary motor and sensory neuropathy ; PMP22 ; vincristine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background:Severe up to life-threatening neuropathy has beenobserved in patients with hereditary neuropathies receiving vincristine. Case report:A 52-year-old female painter suffering fromhigh-grade non-Hodgkin's lymphoma (stage IVB) was treated with a total of 4mg of vincristine during two courses of CHOP chemotherapy (cyclophosphamide,vincristine, adriamycin, prednisone). At onset of treatment no neurologicalproblems were reported. There was good lymphoma response to chemotherapy. Atthe same time, however, the patient gradually developed dysphagia, dysarthria,muscular weakness of both lower and upper extremities, areflexia, paraesthesiaof the fingertips and bilateral sensory impairment of feet and lower legs.These symptoms continually worsened over a period of seven weeks until she wasunable to walk or to perform her work. Electrophysiological studies showedperipheral axonal and demyelinative sensorimotor neuropathy in correlation tohistological findings. Molecular analysis revealed 17p11.2 duplication typicalfor Charcot–Marie–Tooth disease IA. While continuing chemotherapywithout the use of vincristine the patient's neurologic symptoms slowlyrecovered within six months. Conclusion:Prior to administration of vincristine family andpatient history as well as physical examination should be performed carefullyto look for underlying hereditary neuropathy. For those patients with aclinical history or symptoms suggestive for CMT nerve conduction velocitystudies and on an individual base even molecular genetic analysis areneccessary to prevent serious neurologic complications.
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    URL: http://dx.doi.org/10.1023/A:1008369315240
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  • 100
    Electronic Resource
    Electronic Resource
    Chemotherapy in advanced androgen-independent prostate cancer 1990–1999: A decade of progress? (2000)
    Springer
    Annals of oncology 11 (2000), S. 1523-1530 
    Details
    ISSN: 1569-8041
    Keywords: androgen-independent prostate cancer ; chemotherapy ; metastatic prostate cancer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background and purpose:A great number of clinical researchstudies have been reported in the field of chemotherapy for advancedandrogen-independent prostate cancer during the last ten years. The aims ofthe present review were to assess their impact on management of the diseaseand on survival of patients. Methods:The review of full published reports was facilited by theuse of a MEDLINE computer search. Results:Clinical research studies have focused on definingguidelines for eligibility criteria and accurate endpoints for patients to beenrolled onto clinical trials and developing new agents or combinationof drugs including estramustine phosphate. Any combination of currentchemotherapy has no impact on overall survival of patients. Among drugs indevelopment, only the promising activity observed with docetaxel deservesrandomized trials to assess its impact on survival. The major innovativeadvance of the 90s is the demonstration of the impact of chemotherapy(mitoxantrone + prednisone) on quality of life as compared to prednisonealone. A greater and longer-lasting improvement in quality of life along witha concomitant decrease in costs was observed. Conclusions:At the present time, chemotherapy should beconsidered as a palliative treatment in patients with symptomaticandrogen-independent disease. The enrollment of patients into clinical trialsdealing with quality of life as primary endpoint is strongly solicited. Astandard methodology should be used in phase II trials with a primary goal ofselection of agents which should progress to randomized trials using survivalas an endpoint. Hopefully new specific strategies targeted to reverse themolecular changes that underlie prostate tumorigenesis should rapidly impactthe multimodality management of AIPC in the third millenium.
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    URL: http://dx.doi.org/10.1023/A:1008394823889
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