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  • Hodgkin's disease  (3)
  • Acetat  (1)
  • Earthquake  (1)
  • 1
    Electronic Resource
    Electronic Resource
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008301225839
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  • 2
    Electronic Resource
    Electronic Resource
    BEACOPP: A new regimen for advanced Hodgkin's disease (1998)
    Springer
    Annals of oncology 9 (1998), S. 67-71 
    Details
    ISSN: 1569-8041
    Keywords: chemotheapy ; dose escalation ; efficacy ; Hodgkin's disease ; toxicity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The BEACOPP chemotherapy regimen for advanced Hodgkin's disease employs a rearranged schedule permitting a shortened three-week cycle. With haematological growth factor support, the dosages of cyclophosphamide, etoposide and adriamycin could be moderately escalated. The 3-armed multicentre HD9 trial (recruitment 1993-1998; 1300 patients randomised) aimed to compare BEACOPP with the standard COPP/ABVD chemotherapy and to detect and measure the gain in efficacy, if any, due to moderate dose escalation of BEACOPP. Eight cycles were given, followed by local irradiation. The most recent interim analysis, with 689 evaluable patients, circa 40% of all expected events and a median observation time of 27 months, showed significant differences in progression rate (P) and in two-year freedom from treatment failure (F) between the treatment arms, with escalated BEACOPP (P = 2%, F = 89%) better than baseline BEACOPP (P = 9%, F = 81%) better than COPP/ABVD (P = 13%, F = 72%). Survival was not significantly different. Acute toxicity was more severe due to dose escalation, but remained manageable. These preliminary results suggest that BEACOPP improves efficacy. Moderate dose escalation is feasible with G-CSF support and appears likely to make a worthwhile improvement in the cure rate. The results must await confirmation (or otherwise) by the final analysis including all randomised patients and sufficiently mature data.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008451300320
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  • 3
    Electronic Resource
    Electronic Resource
    Model based development of the BEACOPP regimen for advanced stage Hodgkin's disease (1998)
    Springer
    Annals of oncology 9 (1998), S. 73-78 
    Details
    ISSN: 1569-8041
    Keywords: chemotherapy ; dose response relationship ; Hodgkin's disease ; randomised clinical trials ; statistical models ; tumour growth kinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In this article we summarize the theoretical arguments which led us in the German Hodgkin's Disease Study Group to introduce the BEACOPP-regimen and to initiate a large randomised trial to investigate the role of moderate dose escalation in the treatment of advanced stage Hodgkin's disease. Although some indications for a role of dose were available in the early 1990s no prospective randomised trial had been undertaken. In order to obtain an impression of the shape of the essential dose response characteristic we developed a novel statistical model that could be used to analyse a set of data in which dose variations had occured. The model took tumour growth and chemotherapy effects into account. The model could be applied to clinical data on tumour control and treatment given in a patient population. The model was fitted to the data of 706 patients which had received COPP/ABVD-like regimens. It revealed considerable heterogeneity in chemosensitivity and a positive slope of the doseresponse relationship. The model was used to simulate the effect of various treatment strategies with dose escalation and schedule changes. On the basis of such simulations we predicted that shortening cycle intervals from 4 to 3 weeks should lead to small benefits (about 3% in five-year tumour control rates). In contrast, we predicted that a moderate average dose escalation by 30% of a standard chemotherapy would lead to a potential benefit in the order of 10%-15% in tumour control at five years. Subsequently we searched for a treatment scheme that would permit such a dose escalation. The BEACOPP-scheme was invented to allow the three major myelotoxic substances (cyclophsphamide, adriamycin and etoposide) to be given in the beginning of a cycle. These three substances were then subject to dose escalation in a dose finding trial. G-CSF was introduced to compensate for the myelotoxic effects. The dose level found feasible for a large multicentre setting turned out to be in the required magnitude. The HD9 trial of the GHSG was then initiated to examine whether the predicted dose response curve really exists.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008413113949
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  • 4
    Electronic Resource
    Electronic Resource
    Lipogenesis in Ehrlich ascites tumor cells under anaerobic culture conditions (1979)
    Springer
    Journal of cancer research and clinical oncology 95 (1979), S. 115-122 
    Details
    ISSN: 1432-1335
    Keywords: Acetat ; Anaerobiose ; Lipogenese ; Oktanoat ; Pyruvate ; Tritiiertes Wasser ; Tumor ; Acetate ; Anaerobiosis ; Lipogenesis ; Octanoate ; Pyruvate ; Tritiated water ; Tumor
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Anaerobic culture conditions (95% argon/5% CO2) caused a slightly greater increase in total lipids of Ehrlich ascites tumor cells than a gas phase of 20% O2, 75% N2, 5% CO2. Whereas the rate of [U-14C]acetate incorporation into total lipids and lipid-subclasses rose markedly in the absence of oxygen, a drastic decrease of [U-14C]pyruvate and [1-14C]octanoate incorporation as well as a 30% reduction of 3H incorporation into lipids from tritiated water were observed under these conditions. Since profound changes in the metabolic state of cells cause alterations in the specific activity of the acetyl-CoA pool but do not alter the specific activity of intracellular water, this precursor is considered to be an adequate monitor for lipogenesis under aerobic and anaerobic culture conditions. Therefore, it is concluded that Ehrlich ascites tumor cells are not able to reoxidize NADH/NADPH in the absence of oxygen by a stimulation of biosynthesis of fatty acids as is discussed to be the case in normal cells. The slight increase in total lipids of anaerobically cultured cells seems to be the result of an imbalance between normal uptake and impaired utilization of lipids from serum-supplemented culture medium.
    Notes: Zusammenfassung Unter anaeroben Kulturbedingungen, (95% Argon 5% CO2) stieg der Gesamtlipidgehalt in Ehrlich Ascites Tumorzellen etwas stärker an als unter aeroben Bedingungen (20% O2, 75% N2, 5% CO2). In Abwesenheit von Sauerstoff war der Einbau von [U-14C]Acetat in die Gesamtlipidfraktion als auch in einzelne Lipidklassen, deutlich erhöht, wohingegen ein drastischer Abfall der Einbauraten aus [U-14C]Pyruvat und [1-14C]Oktanoat sowie eine signifikante Verminderung des Einbaus von 3H-Wasser unter diesen Kulturbedingungen beobachtet wurde. Da die spezifische Aktivität von intrazellulärem Wasser auch unter tiefgreifenden Änderungen des metabolischen Zustandes der Zellen praktisch konstant bleibt, wird 3H-Wasser als die zuverlässigste Vorstufe zur Messung der Lipidbiosynthese unter aeroben und anaeroben Kulturbedingungen angesehen. Aus den Ergebnissen wird geschlossen, daß Ehrlich Ascites Tumorzellen nicht, wie es für Normalgewebe angenommen wird, in der Lage sind, NADH/NADPH bei Ausschluß von Sauerstoff durch erhöhte Fettsäuresynthese zu, reoxidieren. Der beobachtete Anstieg im Gesamtlipidgehalt von anaerob kultivierten Zellen erklärt sich wahrscheinlich durch ein Ungleichgewicht zwischen normaler Aufnahme und gehemmtem Abbau von exogenen Lipiden.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00401005
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  • 5
    Electronic Resource
    Electronic Resource
    Seismic observations at an overstep of the western North Anatolian Fault (Abant–Sapanca region, Turkey) (1997)
    Springer
    Geologische Rundschau 86 (1997), S. 93-102 
    Details
    ISSN: 0016-7835
    Keywords: Key words Neotectonics ; Seismicity ; Fault-plane solution ; Stress ; Coda Q ; Earthquake ; Micro-earthquake ; Fault ; Pull-apart basin ; Overstep ; Strike slip ; North Anatolian Fault ; Turkey
    Source: Springer Online Journal Archives 1860-2000
    Topics: Geosciences
    Notes: Abstract  The course of the active North Anatolian Fault system from Lake Abant to Lake Sapanca was traced by its high micro-earthquake activity. If approaching from the east this section includes a broad south to north overstep (fault offset) of the main fault. Local seismicity has been recorded in this area by a semi-permanent network of 8 stations since 1985 within the frame of the Turkish–German Joint Project for Earthquake Research. The effect of the overstep and its complex fracture kinematics are reflected by the seismicity distribution, the variations of composite fault-plane solutions, and by the spatial coda-Q distribution. Areas of different stress orientation can be distinguished and assigned to different groups of faults. The stresses and the tectonic pattern only in part correspond to a simple model of an extensional overstep and its correlative pull-apart basin. Other types of deformation involved are characterized by normal faulting on faults parallel to the general course of the main strike-slip fault and by synthetic strike-slip faults oriented similar to Riedel shears. Shear deformation by this fault group widely distributed in an area north and east of the main fault line may play an important role in the evolution of the overstep. The development of a pull-apart basin is inhibited along the eastern half of the overstep and compatibility of both strands of the main fault (Bolu–Lake Abant and Lake Sapanca– Izmit–Marmara Sea) seems to be achieved with the aid of the fault systems mentioned. The extension of the missing part of the pull-apart basin seems to be displaced to positions remote from the Lake Abant–Lake Sapanca main fault line, i.e. to the Akyaz℩–Düzce basin tract. Highest Q-values (lowest attenuation of seismic waves) were found in the zone of highest seismicity north and west of the overstep which is the zone of strongest horizontal tension. If high coda-Q is an indicator for strong scattering of seismic waves it might be related to extensional opening of fractures.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s005310050124
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