Antitumoral activity of oxaliplatin/cisplatin-based combination therapy incisplatin-refractory germ cell cancer patients

Purpose: Only 20-30% of patient with advanced germ cell tumors, relapsing a fter standard first-line therapy, are curable with current second-line cisp latin-based regimens. New salvage combinations incorporating new active age nts are needed. We report the toxicity/tolerance of a new salvage regimen b ased on the oxaliplatin (Eloxatin)/cisplatin combination, evaluated in pati ents with recurrent, mostly cisplatin-refractory germ cell tumors. Patients and methods: Thirteen patients were enrolled in this study. All except one had received cisplatin-based chemotherapy. Eight had progressive disease a s the best response on their last platinum-based chemotherapy, and three ha d potentially sensitive tumors. The median interval since the last platinum -based chemotherapy was 6 months (range: 1-36 months). One untreated patien t with poor prognosis was also enrolled. Twelve patients had pathological m arkers [median alpha-fetoprotein 14 800 ng/ml (58-10(6)), median human chor ionic gonadotrophin beta subunit 7000 IU/ml (37-723 700)]. Patients receive d either oxaliplatin (130 mg/m(2)) and cisplatin (100 mg/m(2)) every 3-4 we eks (Bi regimen, four patients), or the same regimen combined with one to f our of the following cytotoxic agents: ifosfamide, epirubicin, vinorelbine, methotrexate, dactinomycin, etoposide and bleomycin (BIC regimen, 9 patien ts). Treatment was individualized according to each individual patient's pr etreatment and clinical characteristics. Results: Seven objective responses were obtained (overall response rate = 54%), all with the BIC regimens (tw o complete and five partial responses). Two patients with recurrent disease achieved a long-term complete response lasting over 5 years. Four partial responders were seen in the eight cisplatin-refractory tumors, lasting 4-8 months. All objective responses had a corroborating major decrease in tumor marker blood levels (median decrease: 99.7%). The median survival for the whole group was 8 months. The commonest severe toxicity was hematological ( grade 4 neutropenia in 78% and thrombopenia in 74% of the BIC cycles). Conc lusion: Our combined salvage regimen induced significant antitumoral activi ty in recurrent, cisplatin-refractory germ cell tumors. Oxaliplatin merits further evaluation as a component of combination therapy for this disease.