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  • 1
    Electronic Resource
    Electronic Resource
    Sequentielle Induktionschemotherapie und Strahlenbehandlung inoperabler kleinzelliger Bronchialkarzinome (1989)
    Springer
    Journal of molecular medicine 67 (1989), S. 1182-1193 
    Details
    ISSN: 1432-1440
    Keywords: Small cell lung cancer ; Sequential chemotherapy ; Thoracic irradiation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary To study the potential benefit of sequential chemotherapy in inoperable small cell lung cancer (SCLC), from 1982 to 1986 ninety-one patients with histologically proven and previously untreated SCLC (median age: 53 years; median Karnofsky status: 80%) were randomly assigned to an initial therapy with adriamycin (since 1984 epirubicin), cyclophosphamide, vincristine (ACO resp. EPICO) or etoposide/cisplatin (VP16/DDP). Treatment courses were repeated every 3 weeks for a total of ≤6 courses with a crossover after a maximum of 3 cycles of either regimen. Limited disease (LD) patients with bronchoscopical, computertomographical and (re-) mediastinoscopical complete remission (CR) randomly received either a thoracic irradiation with 40 Gy or observation only. Overall, 60 out of 85 evaluable patients achieved an objective remission. A CR was observed in 24/51 patients (47%) with limited disease, and in 8/34 patients (24%) with extensive disease. Both, ACO (EPICO) and VP16/DDP were equally effective as initial and second-line therapy. Moreover, after failure to the initial therapy an objective remission could be achieved in 13% of the patients following the alternative second line combination. In 28% of LD patients with an otherwise complete remission residual tumor was detected by (re-) mediastinoscopy. Median survival times were 14 (CR: 16) months in LD patients and 10 (CR: 15) months in ED patients. At present, median survival is significantly improved in irradiated versus non-irradiated LD patients (25 vs. 13 months, p〈0.04). The remission rates and median survival times observed in this study are comparable to those of a historical control group treated with ACO plus radiotherapy alone.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01716205
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  • 2
    Electronic Resource
    Electronic Resource
    Comparative activity of ifosfamide and cyclophosphamide (1986)
    Springer
    Cancer chemotherapy and pharmacology 18 (1986), S. S1 
    Details
    ISSN: 1432-0843
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Antitumor activity (increase in lifespan and cure) was greater for ifosfamide (IFO) in several experimental tumors, some of which were primarily resistant to cyclophosphamide (CYC). IFO has been shown to be active in anthracycline-resistant and in adriamycin/cisplatin-resistant sublines of an Ehrlich ascites tumor, as well as in tumor cells primarily resistant to CYC. The few comparative controlled clinical trials available suggest superior single-agent activity of IFO compared with CYC in soft tissue sarcoma and ovarian cancer. Combination chemotherapy with IFO has been effective in second-line treatment of sarcomas, malignant lymphomas, lung cancer, and testicular cancer, most of them pretreated with or refractory to CYC. Although it is difficult to obtain clinical proof that there is no cross-resistance between IFO and CYC, IFO has been shown to be active in multirefractory malignant lymphomas, in small cell lung cancer not responding to adriamycin, vincristine, and etoposide, and in soft tissue and bone sarcomas. Testicular cancer and pancreatic cancer are some of the tumors in which IFO activity is currently being evaluated and in which CYC has so far failed to show sufficient clinical activity. More comparative controlled clinical trials are needed in ovarian cancer, breast cancer, malignant lymphomas, sarcomas and cervical cancer, in which IFO has already shown sufficient single-agent activity. Due to its lower level of cross-resistance with a variety of heterocyclic products, but also with other alkylating agents, in addition to its use in induction chemotherapy, IFO is an important second-line agent in many clinical situations.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00647438
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  • 3
    Electronic Resource
    Electronic Resource
    Comparative studies on phenol-soluble nonhistone chromatin proteins in normal and leukaemic human leukocytes (1979)
    Springer
    Journal of molecular medicine 57 (1979), S. 257-265 
    Details
    ISSN: 1432-1440
    Keywords: Phenol-lösliche Chromatinproteine ; menschliche Leukämiezellen ; Adriamycin ; Phenol-soluble chromatin proteins ; Human leukaemia cells ; Adriamycin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Phenol-soluble chromatin proteins which may be involved in gene control mechanisms have been isolated from citric acid nuclei of normal and leukaemic human leukocytes derived from freshly obtained venous blood. They were compared by one-dimensional gel electrophoresis and by comparative labelling with14C-leucine or32P-orthophosphate. In addition, the influence of intercalating agents such as adriamycin and daunomycin was studied. Between 20–35 individual proteins were found in the phenol-soluble nonhistone protein fraction of human leukocytes. They were numbered with increasing mobility on 10% polyacrylamide gels. Distinct differences were found between normal lymphocytes and normal granulocytes, with one specific protein (no. 26 a in lymphocytes; no. 25 in granulocytes) for both cell types. Interestingly, protein no. 25 was not present in CML myelocytes but in CML granulocytes.32P-and leucine labels were generally found decreased with increasing cell differentiation. Leukaemic lymphocytes differed from normal lymphocytes by increased protein concentrations in the high molecular weight region. In comparisons of AML and ALL cells, including blast cells of CML blast crisis, no constant differences nor any markers common to leukaemic cells as compared to normal cells were detectable. However, lymphosarcoma cells showed quantitiative and qualitative aberrations from the usual leukaemia pattern. Afterin vitro incubations of cells with adriamycin a selective decrease of an individual protein (no. 30) was noted. This protein may serve as a marker for the intercalation site.
    Notes: Zusammenfassung Phenol-lösliche Chromatinprotein wurden aus Zellkernen normaler und leukämischer menschlicher Leukozyten isoliert. Die Proteine, deren Bedeutung im Rahmen der Kontrolle des Transkriptionsvorganges diskutiert wird, wurden durch Analyse ihrer gelelektrophoretischen Verteilungsmuster und ihrer Markierung mit14C-Leuzin oder32P-Orthophosphat verglichen. Außerdem wurde der Einfluß interkalierender Agentien wie Adriamycin untersucht. Die Fraktion phenol-löslicher Nicht-Histon-Proteine des Chromatins menschlicher Leukozyten enthält mindestens 20–35 individuelle Proteine, welche mit zunehmender Laufgeschwindigkeit auf 10%-Polyacrylamidgelen numeriert wurden. Zwischen normalen Lymphozyten und normalen Granulozyten ergaben sich charakteristische Unterschiede mit jeweils einer spezifischen Proteinbande (Nr. 26a bei Lymphozyten; Nr. 25 bei Granulozyten) für beide Zelltypen. Interessanterweise war das Protein Nr. 25 in Myelozyten (CML) nicht vorhanden, jedoch in reifen Granulozyten desselben Patienten (CML) nachweisbar. Die radioaktiven Markierungen der Proteine mit32P (Phosphorilierung) bzw.14C-Leuzin (Umsatz) nahmen ganz allgemein mit zunehmender Zelldifferenzierung ab. Leukämische Lymphozyten unterschieden sich von normalen Lymphozyten durch erhöhte Protein-Konzentrationen im hochmolekularen Bereich. Beim Vergleich von Zellen aus AML, ALL und der CML-Blastenkrise ergaben sich bei weitgehend ähnlichen Mustern keine typischen Differenzen. Ebenso waren gemeinsame leukämiespezifische Abweichungen gegenüber Normalzellen nicht nachzuweisen. Lymphosarkomzellen zeigten allerdings quantitative und qualitative Abweichungen vom gewöhnlichen Verteilungsmuster der Zellkernproteine. Nach Einwirkung von Adriamycin in vitro kam es bei den verschiedensten Zellinien dosisabhängig zu einer selektiven Abnahme eines bestimmten Proteins (Nr. 30) dessen mögliche Funktion als „marker“ für den Interkalationslocus von Adriamycin an der DNA diskutiert wird.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01476506
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  • 4
    Electronic Resource
    Electronic Resource
    Cystostatic efficacy of DNA-complexes of adriamycin, daunomycin, and actinomycin D (1977)
    Springer
    Journal of cancer research and clinical oncology 90 (1977), S. 307-312 
    Details
    ISSN: 1432-1335
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Die cytostatische Wirksamkeit der Antibiotica Adriamycin, Daunomycin und Actinomycin D sowie der entsprechenden DNA-Komplexe dieser Verbindungen wurde an einem Ehrlich-Ascitestumor in vivo verglichen. Die Substanzen wurden in verschiedenen Dosierungen jeweils 8 Tage nach Transplantation von 106 Ehrlich Ascites Tumorzellen bei weiblichen NMRI-Mäusen in einmaligen Dosen intraperitoneal verabreicht. Überlebensanalysen der so behandelten Versuchstiere wiesen durchweg auf eine Verbesserung des therapeutischen Index der DNA-Komplexe gegenüber den freien Cytostatica. Da in einer ersten Mitteilung (Seeber et al., 1977) aufgrund biochemischer Studien eine verminderte Cytotoxizität der DNA-Komplexe nachgewiesen werden konnte, beruht die jetzt gefundene Verbesserung der Wirksamkeit in vivo wahrscheinlich auf Veränderungen pharmakologischer Eigenschaften mit einer zeitlichen Verlängerung wirksamer intraperitonealer Cytostaticakonzentrationen bei möglicherweise verminderter systemischer Toxizität.
    Notes: Summary The cytostatic efficacy of the antibiotics adriamycin, daunomycin and actinomycin D and of DNA-complexes of these compounds was compared in an Ehrlich ascites tumor in vivo. Various doses of the individual drugs and their DNA-complexes were injected intraperitoneally into female NMRI mice following 8 days after inoculation of 106 Ehrlich ascites cells. Survival analyses of animals demonstrated that by addition of DNA therapeutic indices were improved for adriamycin, daunomycin and actinomycin D. DNA alone had no effect on this tumor. Since earlier biochemical data (Seeber et al., 1977) had shown decreased in vitro cytotoxicity of DNA-bound antibiotics, this increase in therapeutic efficacy is probably due to an altered pharmacological behaviour after complex formation with a prolongation of effective intraperitoneal drug levels and decreased systemic toxicity.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00284304
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  • 5
    Electronic Resource
    Electronic Resource
    Zum Problem der prätherapeutischen Sensibilitätsbestimmung von Tumoren durch Inkorporationsstudien in vitro (1977)
    Springer
    Journal of molecular medicine 55 (1977), S. 1127-1136 
    Details
    ISSN: 1432-1440
    Keywords: Praetherapeutic sensitivity testing ; Human solid tumours ; Nucleic acid precursors ; Prätherapeutische Sensibilitätsbestimmung ; Menschliche solide Tumoren ; Nukleinsäurevorläufer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Prätherapeutische Sensibilitätsbestimmungen an menschlichen Tumoren auf der Basis von Nukleinsäurevolräufer-Inkorporationsstudien sind von verschiedenen Arbeitsgruppen beschrieben worden. Diese Übersicht will zeigen, weshalb solche Tests für eine dringend erforderliche individuelle Chemotherapieplanung vorerst nur von geringem Nutzen zu sein scheinen. Einer der wesentlichsten Gründe ist, daß es gegenwärtig für viele Zytostatika noch keinen Nachweis einer Korrelation zwischen biochemischer und klinischer Wirkung gibt. Darüber hinaus wird der Aussagewert von Sensibilitätsbestimmungen beeinträchtigt durch methodische Probleme bei der In-vitro-Dosierung und der Zellaufbereitung, die unterschiedliche Pharmakologie und Toxikologie der einzelnen Zytostatika sowie deren Wechselwirkungen bei der kombinierten Chemotherapie.
    Notes: Summary Praetherapeutic sensitivity tests of human solid tumours based on incorporation studies of nucleic acid precursors have been described by various authors. This review intends to show that such tests may only be of rather limited value for the design of individual chemotherapeutic regimens. In many drugs, a correlation between biochemical and clinical effects has not yet been established. The reliability of praetherapeutic sensitivity tests is further impaired by general methodological difficulties of short-term cultures, individual pharmacology and toxicology of cytostatic agents as well as pharmacological and biochemical drug interactions in combination chemotherapy. Praetherapeutic testing with individual cytostatic drugs is discussed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01478050
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  • 6
    Electronic Resource
    Electronic Resource
    Adriamycin, Cyclophosphamid und Fluorouracil in der Therapie des metastasierenden Mamma-Carcinoms (1976)
    Springer
    Journal of cancer research and clinical oncology 86 (1976), S. 135-145 
    Details
    ISSN: 1432-1335
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung In einer prospektiven Studie wurden 11 Patientinnen mit metastasierendem Mamma-Carcinom mit einer Cytostaticakombination aus Fluorouracil, Adriamycin und Cyclophosphamid (FAC) behandelt. Bei drei Patientinnen konnte eine Vollremission (vollständiger Rückgang aller meßbaren Tumorparameter für mehr als 4 Wochen) erreicht werden, die in zwei Fällen (4 und 13 Monate) noch andauert. Partielle Remissionen (Größenabnahme der meßaren Herde über 50% für mehr als 4 Wochen) wurden in 5 Fällen verzeichnet, von denen 3 noch anhalten. Die Zeit bis zum Erreichen der Remissionen betrug 1–3 Monate. Die mittlere Dauer der Vollremission lag bei mehr als 13 Monaten, die der Teilremissionen bei 6,5 Monaten. Zwei Patientinnen zeigten einen Stillstand des Metastasenwachstums über 4 und mehr als 11 Monate. Nur in einem Fall kam es zur Krankheitsprogression. Die mittlere Überlebenszeit ab Beginn der Cytostaticatherapie betrug für die gesamte Patientinnengruppe dieser Studie 7,5 Monate. Für die Fälle mit Voll- und Teilremission lag sie bei mehr als 18 Monaten. Außer in einem Fall wurde die Therapie regelmäßig auf ambulanter Basis durchgeführt. Tierexperimentelle Untersuchungen über den therapeutischen Synergismus von Adriamycin, Cyclophosphamid und Fluorouracil und der Vergleich mit den Remissionsraten unter der alleinigen Kombination aus Adriamycin und Cyclophosphamid lassen weitere Untersuchungen zur optimalen Cytostaticakombination für die Remissionsinduktion des metastasierenden Mamma-Carcinoms notwendig erscheinen.
    Notes: Summary In a prospective study eleven patients with metastasizing breast cancer were treated with 5-fluorouracil, adriamycin, and cyclophosphamide (FAC). Complete remission occurred in three patients, with two of them still in remission four and thirteen months later. Partial remission (50% decrease in tumour size for more than four weeks) was achieved in five cases, with three of them still in remission. Time for remission induction was one to three months. The mean duration of complete remissions is not yet reached after thirteen months, that of partial remissions was 6.5 months. Two patients showed stable disease for four and more than eleven months, respectively. Only in one case progressive disease was noticed. Mean survival time from the start of therapy was 7.5 months for all patients. For complete and partial responders mean survival is not yet reached after eighteen months. With one exception therapy was given on an outpatient basis. Experimental and clinical data on therapeutic synergism of adriamycin, cyclophosphamide, and 5-fluorouracil show no advantage of the three-drug combination over the combination of adriamycin and cyclophosphamide alone.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00284001
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