Methotrexate, etoposide, ifosfamide and cisplatin (MVIP): an effective first-line therapy for IGCCC intermediate /...

To evaluate the antitumor activity and toxicity of methotrexate (M), etoposide (V), ifosfamide (I) and cisplatin (P) combination chemotherapy (MVIP) administered to chemotherapy-naive patients with intermediate / poor prognosis germ-cell tumors (GCT) according to the International Germ Cell Cancer Collaborative Group (IGCCCG) consensus classification system (IGCCC).

From 1992 to 2001 24 consecutive intermediate (n=14)/poor prognosis (n=10) GCT male patients entered prospectively this phase II trial. Patients received methotrexate 250 mg/m(2), day 1, with folinic acid rescue; cisplatin 100 mg/m(2) with appropriate hydration, day 3; ifosfamide 5 g/m(2) with mesna uroprotection, day 3; and etoposide 100 mg/m(2)/day, days 3-5. MVIP was repeated every 3 weeks.

After 120 cycles of MVIP (median 5, range 2- 7) 18 (75%) patients achieved complete remission (CR). CR was attained by 12 out of 14 (86%) intermediate prognosis and 6 out of 10 (60%) poor prognosis patients. Three CR patients (2 intermediate, 1 poor prognosis) of out 18 (16.7%) relapsed after a median of 6 months and 1 of them (poor prognosis) achieved a durable CR with second-line chemotherapy. After a median follow-up of 37 months (range 5-115 months) 16 patients (10, 71% intermediate and 6, 60% poor prognosis) are long-term survivors with no evidence of disease (NED), and 2 (one of each group) are alive with disease. Actuarial overall survival at 3 and more years is 75% and NED survival is 67%. Hematologic toxicity was most common and easily manageable (grade 3-4 neutropenia 46% of the cycles and thrombocytopenia 25% of the cycles). There were no deaths, withdrawals or delays in chemotherapy administration because of toxicity.

MVIP conventional chemotherapy proved very effective in terms of CR rate, overall survival and longterm NED survival in these unfavorable groups of GCT patients. The results obtained are encouraging and compare favorably with those taken by more intensive regimens including high-dose chemotherapy. We believe that MVIP justifies further studies.