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
Autor: | George J. Bosl, Vaia Vlamis, Dean F. Bajorin, Madhu Mazumdar, Subhash C. Gulati, Robert J. Motzer, P Lyn |
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Rok vydání: | 1993 |
Předmět: |
Adult
Male Cancer Research medicine.medical_specialty Adolescent medicine.medical_treatment Urology Vinblastine Carboplatin Bleomycin chemistry.chemical_compound Antineoplastic Combined Chemotherapy Protocols medicine Humans Cyclophosphamide Neoadjuvant therapy Etoposide Bone Marrow Transplantation Cisplatin Chemotherapy business.industry Induction chemotherapy Combined Modality Therapy Survival Analysis Chemotherapy regimen Surgery Regimen Oncology chemistry Dactinomycin Germinoma business medicine.drug |
Zdroj: | JNCI Journal of the National Cancer Institute. 85:1828-1835 |
ISSN: | 1460-2105 0027-8874 |
Popis: | BACKGROUND 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. PURPOSE 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). METHODS 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. RESULTS 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. CONCLUSIONS 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. IMPLICATIONS 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. |
Databáze: | OpenAIRE |
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