Combination Chemotherapy in Treating Male Patients With Germ Cell Tumors

OBJECTIVES:

Primary

• Compare the response rate in patients with poor-prognosis extracranial nonseminoma germ cell tumors treated with intensive induction chemotherapy comprising cisplatin, vincristine, bleomycin, and carboplatin followed by bleomycin, etoposide phosphate, and cisplatin (BEP) vs standard BEP chemotherapy.

Secondary

• Compare overall and progression-free survival of patients treated with these regimens.
• Compare the toxicity of these regimens in these patients.

OUTLINE: This is a multicenter, open-label, randomized study. Patients are stratified according to participating center, pre-protocol low-dose chemotherapy (yes vs no), and other clinically important factors. Patients are randomized to 1 of 2 treatment arms.

• Arm I (BEP): Patients receive bleomycin IV over 15 minutes once on day 1 or 2 and days 8 and 15 and etoposide phosphate IV over 1 hour and cisplatin IV over 4 hours on days 1-5. Treatment repeats every 21 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.
• Arm II (CBOP/BEP): Patients receive chemotherapy according to the following schedule:

• Weeks 1-6: Patients receive cisplatin IV over 6 hours on days 1, 2, 8, 15, 16, and 22 (OR over 4 hours on days 1-5 and 15-19); vincristine IV on days 1, 8, 15, 22, 29, and 36; bleomycin IV over 15 minutes on days 1, 15, 29, and 36 and bleomycin IV continuously on days 8-12 and 22-25; and carboplatin IV over 30-60 minutes on days 8 and 22.
• Weeks 7-15: Patients receive bleomycin IV continuously on days 1-5, 8-12, and 15-19 and etoposide phosphate IV over 1 hour and cisplatin IV over 4 hours on days 1-5. Treatment repeats every 21 days for 4 courses.

After completion of study treatment, patients are followed periodically for 5 years.

Peer Reviewed and Funded or Endorsed by Cancer Research UK

PROJECTED ACCRUAL: A total of 88 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• Nonseminoma germ cell tumor of any extracranial primary site diagnosed by 1 of the following methods:

• Histologic confirmation
• Alpha-fetoprotein (AFP) > 1,000 ng/mL or human chorionic gonadotropin (hCG) > 5,000 IU/L with appropriate clinical picture in a man < 45 years of age
• Poor prognosis features as defined by ≥ 1 of the following:

• AFP > 10,000 ng/mL
• hCG > 50,000 IU/L
• Lactic dehydrogenase > 10 times normal
• Nonpulmonary visceral metastases
• Mediastinal primary site

PATIENT CHARACTERISTICS:

• Male
• WHO performance status 0-3
• Glomerular filtration rate > 50 mL/min

• Less than 50 mL/min eligible if due to obstructive neuropathy that can be relieved by stenting or nephrostomy
• No comorbid condition that would prevent treatment
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

• No prior chemotherapy except low-dose chemotherapy to stabilize disease before study therapy