A phase II study of irinotecan, paclitaxel and oxaliplatin (IPO) in patients with multiply relapsed germ cell tumours (GCT)

Abstract

4527 Background: We have shown that many patients who have viable GCT at surgery, following chemotherapy have enhanced topoisomerase 1 staining on immuno-histochemistry. We have also found that in-vitro the combination of oxaliplatin and SN38 is highly efficacious in the treatment of cisplatin refractory GCT cell lines. Methods: Patients who had failed at least two lines of cisplatin-based therapy (one line in the case of mediastinal tumours) were treated with a novel protocol IPO (oxaliplatin 100mg/m2 on day 1, irinotecan 200mg/m2 on day 1 and paclitaxel 80mg/m2 on day 1, 8 and 15 repeated every 21 days with alternate day filgrastim) to a maximum of 4 cycles. Results: To date 21 patients have been treated of whom 20 were evaluable for response. The median age was 36 years. Eleven were cisplatin sensitive (2 had received prior HDT). Six were refractory and 4 absolutely refractory (AR) according to Beyer’s criteria. A median of 4 cycles was administered. Grade 3/4 toxicity were reported as follows:-alopecia 79%, anorexia 3%, diarrhea 8%, infection 18%, lethargy 16%, vomiting 3%,neutropenia 43%, thrombocytopenia 15%. Response Rate:CR 20%, M-vePR 45%, M+ve PR 15%, SD10% and PD10%. With a median follow up of 13.5 months Seven are currently progression free of whom 2 were AR. Four have had HDT consolidation. Both patients with mediastinal primaries responded to IPO. Two patients who had had prior HDT also responded (CR and m-ve PR). Conclusions: We conclude that IPO is a safe and effective non nephrotoxic salvage therapy in GCT which shows non-cross resistance with previous cisplatin-based chemotherapy. No significant financial relationships to disclose.