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 Journal Article

Authors: Motzer, R. J.; Mazumdar, M.; Gulati, S. C.; Bajorin, D. F.; Lyn, P.; Vlamis, V.; Bosl, G. J.
Article Title: 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
Abstract: 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 cisplatinresistant 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 50000/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 carboplatincontaining 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-intensiveregimen 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. [J Natl Cancer Inst 85: 1828-1835, 1993] © 1993 Oxford University Press.
Keywords: adolescent; adult; cancer survival; clinical article; survival analysis; cisplatin; diarrhea; liver dysfunction; combined modality therapy; drug megadose; carboplatin; nephrotoxicity; phase 2 clinical trial; etoposide; blood toxicity; nausea; vomiting; antineoplastic combined chemotherapy protocols; granulocyte macrophage colony stimulating factor; cyclophosphamide; vinblastine; thrombocyte count; dactinomycin; bleomycin; lactate dehydrogenase; hyperbilirubinemia; leukocyte count; bone marrow transplantation; germ cell tumor; granulocyte; alpha fetoprotein; chorionic gonadotropin; autologous bone marrow transplantation; germinoma; prognosis; human; male; priority journal; article; support, non-u.s. gov't; support, u.s. gov't, p.h.s.
Journal Title: JNCI: Journal of the National Cancer Institute
Volume: 85
Issue: 22
ISSN: 0027-8874
Publisher: Oxford University Press  
Date Published: 1993-11-17
Start Page: 1828
End Page: 1835
Language: English
DOI: 10.1093/jnci/85.22.1828
PUBMED: 7693955
PROVIDER: scopus
Notes: Article -- Export Date: 1 March 2019 -- Source: Scopus
Citation Impact
MSK Authors
  1. Dean Bajorin
    604 Bajorin
  2. Robert Motzer
    1084 Motzer
  3. Madhu Mazumdar
    127 Mazumdar
  4. George Bosl
    422 Bosl
  5. Vaia   Vlamis
    38 Vlamis
  6. Subhash C. Gulati
    124 Gulati