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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Journal of molecular medicine 62 (1984), S. 203-212 
    ISSN: 1432-1440
    Keywords: Tumor heterogeneity ; ‘Short-term assays’ ; DNA damage ; Human tumor-stem cell assay ; Xenograft model
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The evolution of medical oncology so far owes much to the preclinical and clinical development of antineoplastic agents. Prognostic factors and empiric treatment strategies have guided the clinician in his choice of drugs. In the light of increasing ethical restrictions met with phase I–II clinical trials and major advances in propagating human tumor cells outside the donor patient, a reappraisal of predictive tests in cancer chemotherapy is warranted. Among ‘short-term assays’ only the determination of steroid-hormone receptor content in tumor tissues has gained clinical acceptance, whereas other methods still suffer from theoretical or practical shortcomings. Both the human tumor stem cell assay and the xenograft model have revealed unique patterns of sensitivity for each individual tumor line. While interindividual heterogeneity among tumors sharing a common site of origin justifies efforts to develop predictive tests, microheterogeneity among tumor samples from the same donor patient limits the potential of this approach. Predictive tests should be performed in conjunction with clinical trials to ensure optimal extraction of information. As additional prognostic factors, they should in the near future accelerate drug development and reduce the hazard of unnecessary drug toxicity without therapeutic benefit.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-1440
    Keywords: Small-cell lung cancer ; Primary resistance ; Relapse ; Vindesine ; Cisplatin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Thirty-eight pretreated patients with primarily resistant [6] or relapsed [32] small-cell lung cancer were treated with a combination of vindesine (3–4 mg/m2) and cisplatin (60–100 mg/m2). Eight patients responded to this therapy with three (8%) complete and five (13%) partial remissions. Minor responses were noted in 12 (32%) additional patients. Chemotherapeutic response was rare in regions of prior irradiation. In the complete remission group survival from start of vindesine/cisplatin therapy lasted 61, 48 and 38 weeks, respectively. In the “less-than-complete-remission” group median survival was 12 weeks. Nausea and vomiting were the prominent side-effects, while only mild to moderate myelosuppression was noticed in most cases. The vindesine/cisplatin combination showed significant activity in heavily pretreated small-cell lung carcinoma. However, the remission rates remain low in this unfavourable condition, which might be due to pronounced chemotherapeutic resistance in previously irradiated areas.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Annals of hematology 49 (1984), S. 471-472 
    ISSN: 1432-0584
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Journal of cancer research and clinical oncology 105 (1983), S. 162-165 
    ISSN: 1432-1335
    Keywords: Aclacinomycin A ; Phase II study ; Refractory neoplasms
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Aclacinomycin A (ACM) is a new anthracycline antibiotic with a reduced cardiac toxicity in animal models. A phase II study was performed in a total of 25 patients, 23 of whom are evaluable for response. All suffered from recurrent and advanced tumors. Pretreatment consisted of at least four different chemotherapeutic agents (range: 4–9). Lung cancer patients (3/9) were irradiated to the mediastinum. Eighteen patients were pretreated with doxo- or daunomycin. The dose for solid tumors was 2–3 mg/kg given on 3 consecutive days every 3 weeks. Leukemia patients received a daily dose of 20 mg/m2, and standard response criteria were used. Marked reductions of leukocyte counts were achieved in leukemia patients. The overall response rate was about 15% in solid tumors, but major objective responses (CR+PR) have not been observed. Myelosuppression was commonly moderate in solid tumor patients, nausea and vomiting were rare, and alopecia was not induced. Cumulative cardiotoxicity was not evaluated in this trial. Treatment with ACM requires further investigation in acute leukemias and solid tumors, not pretreated with anthracycline antibiotics.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-1440
    Keywords: Small cell bronchogenic carcinoma ; Induction therapy ; Maintenance ; Remission rate ; Survival ; Kleinzelliges Bronchialkarzinom ; Induktionsbehandlung ; Erhaltungstherapie ; Remissionsraten ; Überlebenszeiten
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Seit Juli 1978 wurden 103 Patienten mit inoperablem kleinzelligem Bronchialkarzinom mit der Zytostatikakombination Adriamycin, Cyclophosphamid und Vincristin (ACO) behandelt. Im Stadium „limited disease“ (n=64) erfolgte während des zweiten Chemotherapiekurses eine prophylaktische Schädelbestrahlung, nach dem vierten eine konsolidierende thorakale Bestrahlung. Nach Erreichen einer kompletten Remission erhielten die Patienten prospektiv randomisiert Etoposid oder keine weitere spezifische Therapie. Ein objektives Ansprechen konnte bei 88/100 auswertbaren Patienten erzielt werden. Im Stadium „limited disease“ fanden sich 72%, im Stadium „extensive disease“ nur 33% komplette Remissionen. Im Stadium „limited disease“ betrug die hochgerechnete mediane Überlebenszeit 15,8, im Stadium „extensive disease“ 9,3 Monate (p〈0.005). Es leben noch 29 Patienten, 4 rezidivfrei länger als 24 Monate. Patienten mit kompletter Remission hatten eine statistisch signifikant (p〈0.001) längere Überlebenszeit als Patienten mit geringerem Ansprechen. Regelmäßig traten gastrointestinale und hämatologische Nebenwirkungen auf, drei Patienten starben während der Induktionsphase an Infektionen. Die kurzzeitige Induktionsbehandlung verbesserte jedoch den Krankheitsverlauf subjektiv und objektiv. Bisher ist kein positiver Effekt der zyklischen Etoposid-Gabe nach ACO festzustellen.
    Notes: Summary Since July 1978 one hundred and three consecutive patients with unresectable small cell bronchogenic carcinoma were treated with a combination of doxorubicin, cyclophosphamide and vincristine (ACO). In limited disease patients (64) the second chemotherapy course was followed by prophylactic cranial irradiation, the fourth by irradiation towards primary disease sites. Complete responders were randomised to either receive etoposide or no further maintenance therapy. Objective responses were reached in 88/100 evaluable patients, with 72% of complete remissions in limited-stage disease and 33% in extensive disease, respectively. The actuarial median survival time for limited disease patients was 15.8 months compared to 9.3 months in extensive disease (p〈0.005). 29 of the 100 patients remain still alive, 4 for more than 24 months without disease recurrence. The survival advantage of patients reaching complete remissions relative to those who did not is highly significant (p〈0.001). Acute gastrointestinal and hematological side effects were common, with possibly three drug-related deaths from infections during transient granulocytopenia (mean nadir: 600–900 cells/mm3). The present induction regimen using only four courses of chemotherapy produces high complete remission rates on roentgenography and bronchoscopy and improved survival in the majority of patients. Thus far any effectiveness of etoposide-maintenance therapy following ACO could not be substantiated.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1432-1440
    Keywords: Testicular neoplasms ; Stage II ; Combination chemotherapy ; Radiotherapy ; Lymph node dissection ; Testikuläre Tumoren ; Stadium II ; Kombinierte Chemotherapie ; Radiotherapie ; Lymphknoten-Exstirpation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Seit 1975 wurden 140 Patienten mit retroperitoneal-metastasierten nicht-seminomatösen Hodentumoren nach Orchiektomie und retroperitonealer Lymphadenektomie sequentiell alternierend mit den Zytostatika-Kombinationen Velbe/Bleomycin und Adriamycin/Cisplatin plus/minus Radiotherapie behandelt. Davon erhielten 68 Patienten nach totaler retroperitonealer Lymphadenektomie mit postoperativ normalisierten Tumormarkern (Stadium IIA) 6 Chemotherapie-Kurse, woran sich bei 35 Patienten eine Strahlentherapie anschloß. Vierzig Patienten wurden nach subtotaler retroperitonealer Lymphadenektomie oder bei postoperativ erhöhten Tumormarkern (Stadium IIB) und 32 Patienten nach palliativer Lymphadenektomie (Stadium IIC) mit mindestens 12 Chemotherapie-Kursen und fakultativer intermittierender Radiotherapie und/oder Relaparotomie behandelt. Der Vergleich der Behandlungsergebnisse bei den Stadien IIA und IIB ergab unabhängig von der zusätzlichen Radiotherapie nach der „Life-table“-Methode Vier-Jahres-Überlebensraten zwischen 80 und 100%. Diese günstigen Resultate sind mit den Ergebnissen bei 34 nicht adjuvant behandelten Patienten ohne histologisch nachweisbare retroperitoneale Metastasierung (Stadium I) vergleichbar. Ausdruck einer statistisch signifikant schlechteren Prognose bei fortgeschrittener retroperitonealer Metastasierung ist eine Vier-Jahres-Überlebensrate von 12% bei den Patienten im Stadium IIC.
    Notes: Summary Following orchiectomy and retroperitoneal lymph node dissection (RND) 140 patients with stage II non-seminomatous testicular cancer were treated by sequential combination chemotherapy consisting of vinblastine/bleomycin and adriamycin/cis-dichlorodiammineplatinum(II) (DDP), plus/minus radiotherapy. 68 stage IIA-patients (complete RND and normal tumor-markers thereafter) received 6 courses of chemotherapy, followed by radiotherapy in 35 patients. 40 stage IIB-patients (minor residual disease after RND or elevated tumor-markers after RND) and 32 stage IIC-patients (advanced residual disease after RND) were treated by at least 12 chemotherapy courses and optional intermittent radiotherapy and/or relaparotomy. In stage IIA and IIB disease the actuarial 4-year survival rates were between 80 and 100%. These favourable results were not significantly influenced by additional radiotherapy and corresponded to the survival rates for 34 stage I-patients. For stage IIC-patients the prognosis was significantly worse with a 12% 4-year survival rate.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1432-1440
    Keywords: Testicular neoplasms ; Stage IV ; Combination chemotherapy ; Prognosis ; Cross-resistance ; Testikuläre Tumoren ; Stadium IV ; kombinierte Chemotherapie ; Prognose ; Kreuzresistenz
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Vierundsiebzig Patienten mit pulmonal metastasierten nicht-seminomatösen Hodentumoren wurden im Rahmen einer prospektiven randomisierten Phase III-Studie sequentiell alternierend mit Velbe/Bleomycin und Adriamycin/Cisplatin behandelt. Unabhängig von der Randomisierung der initialen Zytostatika-Kombination wurden bei 71 auswertbaren Patienten bei einer Ansprechrate von 89% in 54% der Fälle Vollremissionen erzielt, die bei 35% der Patienten zwischen 2+ und 28+ Monaten mit einem Median von 12 Monaten andauerten. Durch zusätzliche operative Entfernung residueller pulmonaler Solitärmetastasen wurde die Vollremissionsrate auf 40/71 (56%) und die Anzahl der andauernden Vollremissionen auf 27/71 (38%) erhöht. Die Zwei-Jahres-Überlebensrate betrug nach der „Life-table“-Methode 63% bei den Patienten, bei denen eine Vollremission erreicht wurde, und war mit 29% bei den übrigen Patienten statistisch signifikant niedriger. Dreiundfünfzig Patienten (75%) waren bei einer mittleren Überlebenszeit von 9 Monaten zwischen 3 und 28 Monaten am Leben. Zusätzliche fortgeschrittene abdominelle Metastasierung, initial erhöhte β-HCG-und LDH-Werte und das Ausmaß der pulmonalen Metastasierung beeinflußten die Prognose statistisch signifikant negativ. Die Auswertung der einzelnen Chemotherapie-Kurse zeigte, daß beide Zytostatika-Kombinationen gleich wirksam waren. Dabei war jedoch ein Ansprechen auf Adriamycin/Cisplatin in 46% der Fälle nachweisbar, in denen Velbe/Bleomycin versagt hatte, während Velbe/Bleomycin nur bei 21% der Fälle wirksam war, in denen Adriamycin/Cisplatin zu keinem Ansprechen geführt hatte. Eine unterschiedlich ausgeprägte Kreuzresistenz zwischen den beiden Zytostatika-Kombinationen muß daher angenommen werden.
    Notes: Summary 74 patients with disseminated non-seminomatous testicular cancer were randomly entered on a prospective sequential combination chemotherapy regimen with mandatory crossover, consisting of either vinblastine/bleomycin or adriamycin/cis-dichlorodiammineplatinum (II) (DDP) as initial therapy. Independent of the randomization the overall remission rate in 71 evaluable patients was 89% including 54% complete remissions. 35% of the patients remained disease-free at 2+ to 28+ months with a median of 12 months. By additional surgical removal of residual pulmonary metastases in two patients the complete remission rate was increased to 40/71 (56%), and the number of patients with no evidence of disease to 27/71 (38%). According to the life-table method the two-years survival rates were 63% for complete responders and 29% for all other patients, which was significantly lower. 53 patients (75%) were alive at 3 to 28 months with a median of 9 months. Additional advanced abdominal disease, initially elevated β-HCG and LDH and extension of pulmonary disease were of significant negative influence on the prognosis. The evaluation of single chemotherapy courses revealed equal efficacy of both combinations. However, response to adriamycin/DDP occurred in 46% of the courses, when vinblastine/bleomycin had failed, while response to vinblastine/bleomycin occurred only in 21% of the courses when adriamycin/DDP had failed. Thus different patterns of cross-resistance between these alternative regimens may exist.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Journal of cancer research and clinical oncology 107 (1984), S. 57-60 
    ISSN: 1432-1335
    Keywords: Cisplatin ; Phase II study ; Solid tumors
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Seventy-three evaluable patients with advanced measurable solid tumors were given cisdichlorodiammineplatinum (II) (DDP) at a dose of 20 mg/M2 IV for 1–5 days every 3 weeks, and 19 patients who failed on this low dose DDP protocol received a single high dose of 100 mg/M2 IV once every 3 weeks. Forty-six patients had received prior chemotherapy, and 29 patients were untreated. Results included four complete responses (5.5%) in malignant melanoma, spindle-cell sarcoma, adrenal carcinoma, and bladder carcinoma lasting 2 to 4 months. In 21 patients (28.8%), partial responses were achieved. Twenty-two patients (30.1%) showed stable disease and 26 (35.6%) had tumor progression. A response rate of 25% (4/16 patients) was found for malignant melanoma, 45.5% (5/11) for nonsmall-cell lung cancer, and 35.3% (6/17) for sarcomas of various types. One patient with teratocarcinoma, who relapsed on low-dose DDP, had another partial remission for 4 months after high-dose therapy. Toxicity was most commonly seen with gastrointestinal side effects and myelosuppression. Cumulative nephrotoxicity was prevented by prehydration and/or treatment with furosemide or mannitol.
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    Journal of cancer research and clinical oncology 100 (1981), S. 85-93 
    ISSN: 1432-1335
    Keywords: Leydig cell tumor ; Cushing's syndrome ; Klinefelter's syndrome ; o,p′-DDD ; Leydig-Zell-Karzinom ; Cushing-Syndrom ; Klinefelter-Syndrom ; o,p′-DDD
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Wir berichten über einen 39jährigen Patienten mit einem Klinefelter-Syndrom, bei dem sich die autonome Produktion von Cortisol durch einen metastasierenden Leydig-Zell-Tumor nachweisen ließ. Die endokrine Tumoraktivität zeigte sich — neben einem Cushing-Syndrom — in der abnormen Sekretion von Östradiol, Östron, alkalischer Phosphatase und Testosteron. Es handelt sich dabei unseres Wissens um den ersten beschriebenen Fall eines Cushing-Syndroms, das nicht über die Bildung von ACTH, sondern durch ektope Steroidproduktion verursacht wurde. Bei fehlender Radio- und Chemotherapiesensibilität zeigte sich eine Tumorrückbildung während der Behandlung mit o,p′-DDD, die mit einem dauerhaften Abfall der biologischen Tumormarker verbunden ist. Die Ätiologie des Tumors im Zusammenhang mit dem Klinefelter-Syndrom wird besprochen.
    Notes: Summary We present the case of a 39-year-old man with Klinefelter's syndrome and metastatic Leydig cell carcinoma in whom autonomous cortisol production induced by the interstitial cell tumor was found. Apart from the Cushing's syndrome the endocrine activity of the tumor was demonstrated by the secretion of estradiol, estrone, alkaline phosphatase, and testosterone. This is, to our knowledge, the first description of a Cushing's syndrome not caused via ACTH production but directly induced by ectopic steroid production. While being resistent to chemotherapy and radiation, the tumor responded favorably to treatment with o,p′-DDD. The reduction of tumor size was accompanied by a continuous decrease of serum markers. The etiology of the tumor is discussed in the light of the hormonal derangement caused by the genetic abnormality of Klinefelter's syndrome.
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 1432-1335
    Keywords: Synthesis ; Antitumor activity ; Leukemia L 5222 ; ADJ/PC6 Plasmacytoma ; MDA-MB 231 ; Breast cancer cell line ; Cisplatin-, daunomycin-, and cisplatin/daunomycin-resistant Ehrlich ascites tumor lines
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Ring unsubstituted dichloro(diphenylethylenediamine)platinum(II) complexes show a dependence of their antitumor activity on the configuration and position of phenyl rings in ethylenediamine ligand. Dichloro(1,1-diphenylethylenediamine)platinum(II) (1d) and meso-dichloro(1,2-diphenylethylenediamine)-platinum(II) (meso-2d) have a weaker effect on the human breast-cancer cell line MDA-MB 231 and on rat leukemia L5222 than (±)-dichloro(1,2-diphenylethylenediamine)platinum(II) ((+)-2d) and its enantiomers (+)-2d and (-)-2d which cause marked and comparable inhibition of both tumors; (±)-2d is also active on ADJ/PC 6 plasmacytoma of the mouse and on cisplatin-, daunomycin-, and cisplatin/daunomycin-resistant Ehrlich ascites tumors of the mouse. The differences in activity of the diastereomers (±)-2d and meso-2d, for which distinct influences on the DNA secondary structure can be demonstrated CD spectroscopically may be explained by a steric hindrance of the drug-DNA interaction.
    Type of Medium: Electronic Resource
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