Methotrexate, paclitaxel, ifosfamide, and cisplatin in poor-risk nonseminomatous germ cell tumors

Objective: The efficacy and tolerability of M-TIP was evaluated as first-line treatment for patients with poor-risk germ cell tumors (GCT), according 1:0 International Germ Cell Cancer Collaborative Group (IGCCCG) criteria. Patients and methods: Thirty patients with poor-risk GCT were treated with M-TIP (methotrexate 250 mg/m(2) given as a 4-hour infusion with folinic acid rescue on day 1, paclitaxel 175 mg/m2 given as a 3-hour infusion on day 1, followed by ifosfamide 1.2 g/m(2) given as a 2-hour infusion and cisplatin 20 mg/m(2) given as a 2-hour infusion on days 2 to 6) regimen for four cycles. Results: Five (16.6%, 95% confidence interval [CI]: 2%-31%) patients achieved clinical complete response (cCR) with chemotherapy only, 15 (50%, 95% CI: 31-69%) patients pathologic complete response (pCR) (11 had necrosis/fibrosis and 4 had mature teratoma) and 3 (10%) patients surgical complete response (sCR) for an overall favorable response of 76.6%. Twenty-one patients are continuously disease-free at a median follow-up of 5.3 years (range 0.9-8.4+ years), resulting in a 5-year progression-free survival (PFS) rate of 66.6% (95% CI = 49%-35%) and a 5-year survival rate of 70% (95% CI = 53%-87%). Toxicity was generally mild except for myelotoxicity. Patients with febrile neutropenia were successfully treated with broad spectrum antibiotics and G-CSF support. Hematologic toxicity in this trial was ameliorated with the use of G-CSF. Neurotoxicity and nephrotoxicity were not a problem, since only 6.6% and 3.3% of patients developed sensory neuropathy and renal toxicity, respectively. Conclusion: M-TIP is a highly effective (high proportion of patients achieved long-term disease-free status, lack of relapses) and well tolerated regimen for first-line treatment of poor-risk GCT patients. These results have to be compared with the standard BEP chemotherapy or more intensive regimens in multicentre randomized trials. (C) 2010 Elsevier Inc. All rights reserved.