A 20% dose reduction of the original CISCA/VB regimen allows better tolerance and similar survival rate in disseminated testicular non-seminomatous germ-cell tumors: final results of a phase III randomized trial.

Abstract

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: K Fizazi, K A Do, X Wang, L Finn, C J Logothetis, R J Amato
• Journal: Annals of oncology : official journal of the European Society for Medical Oncology (Ann Oncol) Vol. 13 Issue 1 Pg. 125-34 (Jan 2002) ISSN: 0923-7534 [Print] England
• PMID: 11863094 (Publication Type: Clinical Trial, Clinical Trial, Phase III, Journal Article, Randomized Controlled Trial)

Chemical References

• Bleomycin
• Vinblastine
• Doxorubicin
• Cyclophosphamide
• Cisplatin

Topics

• Adolescent
• Adult
• Antineoplastic Combined Chemotherapy Protocols (administration & dosage, adverse effects, therapeutic use)
• Bleomycin (administration & dosage, adverse effects, therapeutic use)
• Cisplatin (administration & dosage, adverse effects, therapeutic use)
• Cyclophosphamide (administration & dosage, adverse effects, therapeutic use)
• Dose-Response Relationship, Drug
• Doxorubicin (administration & dosage, adverse effects, therapeutic use)
• Humans
• Male
• Middle Aged
• Neoplasm Staging
• Neoplasms, Germ Cell and Embryonal (drug therapy, pathology)
• Survival Analysis
• Testicular Neoplasms (drug therapy, pathology)
• Time Factors
• Vinblastine (administration & dosage, adverse effects, therapeutic use)