A phase II multicentre study of oxaliplatin (Ox) in combination with paclitaxel (Px) in patients (pts) who failed cisplatin (CDDP) based chemotherapy (CT) for germ cell tumors (GCT)

Abstract

4534 Background: pts with either CDDP refractory (REF) or with a poor prognosis relapse (REL) GCT, defined as progressing less than 2 or between 2 and 6 months (mos) of CDDP administration respectively have dismal prognosis.Px induces 11 to 26% response rates (RR) in a similar pt population.Ox is a platinum compound with a lack of cross resistance with CDDP. Methods: REF and REL pts, who had received at least one line of CT containing Etoposide+CDDP. Treatment: combination of Px (175 mg/m2, 3h infusion) followed by Ox (130 mg/m2, 2h infusion) administered q3 weeks. Endpoints were RR (WHO criteria) and tumor marker decrease (TMD)>90% or >50%.The 2-step modified Gehan design was used for sample size determination. Results: 26 pts were enrolled; median age 31 yrs (range 18–46); PS 0/1:13/13; 18 had non seminoma (among whom 5 mediastinal primaries), 2 seminoma and 6 mixed GCT; 16 pts were REF and 10 pts were REL; 22, 3 and one pts had previously received 2, 3 and 5 lines of CDDP based CT. A total of 87 cycles (median 4,range 1 to 7) were administered. The worst toxicity (NCI-CTC) consisted in: grade (G) 3 and 4 neutropenia (N) in 3 and 4 pts respectively, G 3 anemia in 3 pts, G 3 thrombocytopenia in one pt, G 3 neuropathy in one pt and G3 infection without N in one pt. One Partial Response with normal TM (lasting 18+ mos) and 4 TMD > 90% and 3 TMD > 50% were observed. Median Time to Tumor Progression and Overall Survival (months) were 2.0 [95% CI :1.5 - 2.5] and 8.8 [95% CI : 5 -12] respectively. However 2 pts were eventually salvaged by surgical exeresis of limited disease and are alive free of disease progression at 13+ and 23+ months respectively. Conclusions: Ox-Px Combination is safe and looks active in refractory and relapsed GCT, it warrants further developments within the treatment strategy in these patients. No significant financial relationships to disclose.