Phase III randomized trial of conventional-dose chemotherapy with or without high-dose chemotherapy and autologous hematopoietic stem-cell rescue as first-line treatment for patients with poor-prognosis metastatic germ cell tumors Journal Article


Authors: Motzer, R. J.; Nichols, C. J.; Margolin, K. A.; Bacik, J.; Richardson, P. G.; Vogelzang, N. J.; Bajorin, D. F.; Lara, P. N. Jr; Einhorn, L.; Mazumdar, M.; Bosl, G. J.
Article Title: Phase III randomized trial of conventional-dose chemotherapy with or without high-dose chemotherapy and autologous hematopoietic stem-cell rescue as first-line treatment for patients with poor-prognosis metastatic germ cell tumors
Abstract: Purpose: To investigate the role of high-dose chemotherapy (HDCT) as first-line treatment in patients with metastatic germ cell tumor (GCT) and poor-prognostic clinical features. Serum tumor marker decline during chemotherapy was assessed prospectively as a predictor of treatment outcome. Patients and Methods: In this randomized phase III trial, previously untreated patients with intermediate- or poor-risk GCT received either four cycles of standard bleomycin, etoposide, and cisplatin (BEP alone), or two cycles of BEP followed by two cycles of HDCT containing carboplatin and then by hematopoietic stem-cell rescue (BEP + HDCT). Serum tumor markers alpha-fetoprotein and human chorionic gonadotrophin were correlated with treatment outcome as a secondary end point. Results: Two hundred nineteen patients were randomly assigned: 108 to BEP + HDCT and 111 to BEP alone. The 1-year durable complete response rate was 52% after BEP + HDCT and 48% after BEP alone (P = .53). Patients with slow serum tumor marker decline (alpha-fetoprotein and/or human chorionic gonadotrophin) during the first two cycles of chemotherapy had a shorter progression-free survival and overall survival compared with patients with satisfactory marker decline (P = .02 and P = .03, respectively). Among 67 patients with unsatisfactory marker decline, the 1-year durable complete response proportion was 61% for patients who received HDCT versus 34% for patients receiving BEP alone (P = .03). Conclusion: The routine inclusion of HDCT in first-line treatment for GCT patients with metastases and a poor predicted outcome to chemotherapy did not improve treatment outcome. Frequent serum marker determinations to estimate marker decline during the first two cycles of BEP chemotherapy provide a clinically useful estimate of outcome. © 2007 by American Society of Clinical Oncology.
Keywords: survival; adolescent; adult; cancer chemotherapy; controlled study; treatment outcome; middle aged; survival analysis; unclassified drug; major clinical study; clinical trial; disease course; cisplatin; drug megadose; antineoplastic agent; prospective study; neoplasm; carboplatin; metastasis; controlled clinical trial; multiple cycle treatment; etoposide; randomized controlled trial; antineoplastic combined chemotherapy protocols; tumor markers, biological; hematopoietic stem cell transplantation; pathology; tumor marker; blood; disease progression; multicenter study; neoplasm metastasis; bleomycin; bep protocol; neoplasms, germ cell and embryonal; phase 3 clinical trial; randomization; germ cell tumor; autologous hematopoietic stem cell transplantation; alpha fetoprotein; chorionic gonadotropin
Journal Title: Journal of Clinical Oncology
Volume: 25
Issue: 3
ISSN: 0732-183X
Publisher: American Society of Clinical Oncology  
Date Published: 2007-01-20
Start Page: 247
End Page: 256
Language: English
DOI: 10.1200/jco.2005.05.4528
PUBMED: 17235042
PROVIDER: scopus
DOI/URL:
Notes: --- - "Cited By (since 1996): 92" - "Export Date: 17 November 2011" - "CODEN: JCOND" - "Source: Scopus"
Altmetric Score
MSK Authors
  1. Dean Bajorin
    413 Bajorin
  2. Robert Motzer
    762 Motzer
  3. Madhu Mazumdar
    123 Mazumdar
  4. George Bosl
    262 Bosl
  5. Jennifer M Bacik
    46 Bacik