BACKGROUND: This prospective randomized clinical trial was designed to compare the efficacy of a low-dose regimen of cisplatin, doxorubicin and cyclophosphamide alternated with vinblastine and bleomycin (CISCA/VB) with the original CISCA/VB regimen in patients with disseminated nonseminomatous germ-cell tumors (NSGCT) and a predicted favorable outcome. PATIENTS AND METHODS: One hundred and twenty-five patients with disseminated NSGCT and a predicted favorable outcome according to the M.D. Anderson Cancer Center classification [testicular primary and human chorionic gonadotropin (hCG) serum level <50000 mIU/ml] were randomized to receive the original CISCA/VB regimen (100% dose) or a low-dose CISCA/VB regimen (80% dose). RESULTS: Among the 124 eligible patients, there was no significant difference in the number of patients in the two treatment arms who achieved a complete response to therapy: 53 of 65 patients (82%) on the original CISCA/VB regimen and 53 of 59 patients (90%) on the low-dose CISCA/VB regimen (P = 0.29). Overall, the original CISCA/VB regimen resulted in a significantly higher relative dose intensity (P <0.0001). After a median follow-up of 6.8 years (range 0.37 to 12.94 years), there was no significant difference in disease-free survival (P = 0.87) or in overall survival (P = 0.88) between the two treatment arms. The 5-year overall survival rate was 93.7% [95% confidence interval (CI) 88% to 100%] and 94.1% (95% CI 84% to 100%) in the original CISCA/VB arm and the low-dose CISCA/VB arm, respectively. The 5-year overall survival rate for the entire study population was 98% (95% CI 94% to 100%) and 88% (95% CI 76% to 100%) in the good- and intermediate-prognosis groups, respectively, as defined by the International Germ Cell Consensus Classification Group (IGCCCG). The low-dose CISCA/VB regimen resulted in significantly less neutropenic fever (P <0.001), grade 4 thrombocytopenia (P <0.03) and severe mucositis (P <0.01) than the original CISCA/VB regimen. CONCLUSIONS:CISCA/VB is highly efficient in patients with good or intermediate prognosis NSGCT according to the IGCCCG criteria. Although equivalent antitumor efficacy cannot be claimed, the low-dose CISCA/VB regimen appears to be a better mode of delivery than the original CISCA/VB regimen with respect to toxicity, since survival is comparable.
RCT Entities:
BACKGROUND: This prospective randomized clinical trial was designed to compare the efficacy of a low-dose regimen of cisplatin, doxorubicin and cyclophosphamide alternated with vinblastine and bleomycin (CISCA/VB) with the original CISCA/VB regimen in patients with disseminated nonseminomatous germ-cell tumors (NSGCT) and a predicted favorable outcome. PATIENTS AND METHODS: One hundred and twenty-five patients with disseminated NSGCT and a predicted favorable outcome according to the M.D. Anderson Cancer Center classification [testicular primary and human chorionic gonadotropin (hCG) serum level <50000 mIU/ml] were randomized to receive the original CISCA/VB regimen (100% dose) or a low-dose CISCA/VB regimen (80% dose). RESULTS: Among the 124 eligible patients, there was no significant difference in the number of patients in the two treatment arms who achieved a complete response to therapy: 53 of 65 patients (82%) on the original CISCA/VB regimen and 53 of 59 patients (90%) on the low-dose CISCA/VB regimen (P = 0.29). Overall, the original CISCA/VB regimen resulted in a significantly higher relative dose intensity (P <0.0001). After a median follow-up of 6.8 years (range 0.37 to 12.94 years), there was no significant difference in disease-free survival (P = 0.87) or in overall survival (P = 0.88) between the two treatment arms. The 5-year overall survival rate was 93.7% [95% confidence interval (CI) 88% to 100%] and 94.1% (95% CI 84% to 100%) in the original CISCA/VB arm and the low-dose CISCA/VB arm, respectively. The 5-year overall survival rate for the entire study population was 98% (95% CI 94% to 100%) and 88% (95% CI 76% to 100%) in the good- and intermediate-prognosis groups, respectively, as defined by the International Germ Cell Consensus Classification Group (IGCCCG). The low-dose CISCA/VB regimen resulted in significantly less neutropenic fever (P <0.001), grade 4 thrombocytopenia (P <0.03) and severe mucositis (P <0.01) than the original CISCA/VB regimen. CONCLUSIONS: CISCA/VB is highly efficient in patients with good or intermediate prognosis NSGCT according to the IGCCCG criteria. Although equivalent antitumor efficacy cannot be claimed, the low-dose CISCA/VB regimen appears to be a better mode of delivery than the original CISCA/VB regimen with respect to toxicity, since survival is comparable.
Authors: Hans-Georg Kopp; Markus Kuczyk; Johannes Classen; Arnulf Stenzl; Lothar Kanz; Frank Mayer; Michael Bamberg; Jörg Thomas Hartmann Journal: Drugs Date: 2006 Impact factor: 9.546
Authors: S D Fosså; B Paluchowska; A Horwich; G Kaiser; P H M de Mulder; O Koriakine; A T van Oosterom; L de Prijck; L Collette; R de Wit Journal: Br J Cancer Date: 2005-11-28 Impact factor: 7.640
Authors: K Fizazi; D M Prow; K-A Do; X Wang; L Finn; J Kim; D Daliani; C N Papandreou; S-M Tu; R E Millikan; L C Pagliaro; C J Logothetis; R J Amato Journal: Br J Cancer Date: 2002-05-20 Impact factor: 7.640