Salvage chemotherapy with irinotecan and nedaplatin for cisplatin refractory germ cell tumors

Abstract

e16022 Background: Only 20 - 30 % of patients with cisplatin (CDDP) refractory germ cell tumor (GCT) will remain continuously disease-free with salvage chemotherapy. The present study investigated the combination chemotherapy with irinotecan (Ir) and nedaplatin (CDGP), the second generation derivative of CDDP developed in Japan, as salvage chemotherapy for CDDP-refractory GCT. Methods: Between June 1998 and December 2007, 39 CDDP refractory GCT patients treated with irinotecan and CDGP (IrN therapy) were assessed retrospectively. IrN therapy consisted of Ir: 100–150 mg/m2 on day 1, 15 or 200–300 mg/m2 on day 2, CDGP: 100 mg/m2 on day 1 every four weeks with oral administration of Chinese-herb ‘Hange-shashinto’ and sodium bicarbonate for diarrhea. After tumor marker normalization, residual masses were resected and chemotherapy was continued in the case of without marker normalization. Results: The median age was 31 years old (range; 17–48). The median number of cycles of prior chemotherapy was 6 (range; 2–30). The median number of cycles of IrN therapy was 3 (range: 1–9). The response rate was 30.8% ( CR: 0%, PRm−: 15.4%, PRm+: 15.4% ) and the outcome was no evidence of disease (NED) 46.2%, alive with disease (AWD) 25.6% and dead 28.2%, respectively. Twenty-five patients with IrN therapy as 2nd (17 cases) and 3rd (8 cases) line salvage therapy showed that the response rate was 48% (CR: 0%, PRm−: 16.0%, PRm+: 16.0, NCm−: 16.0%) and the outcome was as follows; NED 64%, AWD 16% and dead 20%, respectively. On the other hand, 14 pts who had the treatment as fourth-line or more showed less response rate (PR: 28.5%) and worse outcome (NED 14.2%). Major adverse events more than grade 3 were neutropenia and thrombocytopenia. These adverse events were manageable. Grade 4 diarrhea which was major adverse event of CPT-11 was observed in only one case and there was no treatment related death. Conclusions: This study demonstrates that combination chemotherapy with CPT-11 and CDGP showed significant anticancer activity for patients with CDDP-refractory GCT without severe adverse events. These findings suggest that salvage IrN therapy may be one of the options as second- or third-line therapy. No significant financial relationships to disclose.