Ifosfamide in Germ Cell Tumors

Ifosfamide has always had significant single-agent activity in patients with germ cell tumors. We first began studies of cisplatin + ifosfamide combination chemotherapy as salvage chemotherapy in 1982. The regimen of etoposide (VP-16) + ifosfamide + cisplatin (VIP) was initially utilized as third-line chemotherapy. Even in this refractory setting, we were able to cure a small cohort of patients. Ifosfamide-cisplatin combination chemotherapy then became a standard second-line chemotherapy program, and achieved a 25% cure rate. Subsequent phase III studies compared VIP to bleomycin + etoposide + cisplatin (BEP) as initial chemotherapy. Although the results of the ifosfamide-based regimen were slightly better, there was no statistically significant difference and BEP was less toxic. However, for individual patients with concern for bleomycin-induced pulmonary fibrosis, VIP remains an attractive first-line regimen.