Phase II trial of high-dose carboplatin and etoposide with autologous bone marrow transplantation in first-line therapy for patients with poor-risk germ cell tumors

• Published in: JNCI : Journal of the National Cancer Institute Vol. 85; no. 22; p. 1828
• Main Authors: Motzer, R J, Mazumdar, M, Gulati, S C, Bajorin, D F, Lyn, P, Vlamis, V, Bosl, G J
• Format: Journal Article
• Language: English
• Published: United States 17-11-1993
• Subjects: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Bleomycin - administration & dosage; Bone Marrow Transplantation; Carboplatin - administration & dosage; Cisplatin - administration & dosage; Combined Modality Therapy; Cyclophosphamide - administration & dosage; Dactinomycin - administration & dosage; Etoposide - administration & dosage; Germinoma - drug therapy; Germinoma - therapy; Humans; Male; Survival Analysis; Vinblastine - administration & dosage
• ISSN: 0027-8874
• DOI: 10.1093/jnci/85.22.1828

Between 20% and 30% of patients with advanced germ cell tumors (GCTs) fail to have durable complete response to conventional cisplatin-based induction chemotherapy. However, third-line therapy with high-dose carboplatin and etoposide plus autologous bone marrow transplantation (AuBMT) has induced durable complete response in 10%-20% of patients with cisplatin-resistant GCT.
We conducted a phase II trial of first-line therapy that included high-dose carboplatin and etoposide plus AuBMT in untreated men with advanced GCTs and unfavorable prognosis (i.e., "poor-risk" patients).
Twenty-eight patients were treated with a conventional-dose, cisplatin-containing regimen (VAB-6 [cisplatin, vinblastine, bleomycin, cyclophosphamide, dactinomycin]) with or without high-dose carboplatin (1500 mg/m2) and etoposide (1200 mg/m2) plus AuBMT. Twenty-two of these patients were selected for treatment with two cycles of high-dose carboplatin and etoposide plus AuBMT when reduced clearance of serum tumor markers (alpha-fetoprotein [AFP] or human chorionic gonadotropin [HCG]), as evidenced by prolonged half-life (> 7 days for AFP and > 3 days for HCG), was observed after two cycles of conventional treatment.
Fifteen (56%) of 27 patients considered assessable for response achieved a complete response (12 treated with high-dose chemotherapy plus AuBMT). Sixteen (57%) are alive; 13 (46%) are free of disease at a median follow-up of 31.2 months. For 36 cycles of high-dose chemotherapy, the median duration from bone marrow infusion until a granulocyte count of 0.5/mm3 and a platelet count of 50,000/mm3 was 16 days (range, 7-41 days and 8-30 days, respectively). Analysis showed a trend toward improved survival (P = .07) in patients treated with high-dose chemotherapy in this study, compared with 68 poor-risk patients with GCT treated with conventional-dose therapy alone in two earlier studies. Toxicity was not cumulative, and recovery of blood counts after AuBMT was generally rapid.
Inclusion of high-dose carboplatin-containing chemotherapy in treatment of poor-risk GCT patients is feasible when serum tumor marker half-life is used to predict resistance to standard cisplatin-based therapy. High-dose therapy in this setting was well tolerated.
Early use of a dose-intensive regimen may increase survival compared with conventional-dose therapy alone. Further studies with standard induction therapy and intensive high-dose therapy using hematopoietic growth factor support are warranted, followed by a randomized trial comparing this strategy with standard therapy.