The efficacy of irinotecan, paclitaxel, and oxaliplatin (IPO) in relapsed germ cell tumours with high-dose chemotherapy as consolidation: a non-cisplatin-based induction approach

Objectives To determine the outcome of an expanded cohort of patients with relapsed germ cell tumours (GCTs) treated with a salvage chemotherapy regimen consisting of irinotecan, paclitaxel and oxaliplatin (IPO) and assess the role of IPO as an alternative to standard cisplatin-based chemotherapy regimens in this setting. Patients and Methods The results of 72 consecutive patients were reviewed retrospectively. IPO was used either as a second-line treatment (29 patients), of which 20 patients subsequently received high-dose chemotherapy (HDCT), or third-line (43), of which 32 patients proceeded to HDCT. Results The 2-year progression-free survival (PFS) and 3-year overall survival (OS) rates for the whole cohort were 30.2% (95% confidence interval [ CI] 17.3-40.5%) and 33.4% (95% CI 20.1-43.8%), respectively. Complete remission was achieved in 3%, marker-negative partial response (PR) in 41%, marker-positive PR in 18%, stable disease in 17% and progressive disease in 20%. In the second-line setting, the 2-year PFS rate was 43.5% 95% CI 21.7-60.8%) and 3-year OS 49.1% 95% CI 24.2-65.1%). In the third-line setting, the 2-year PFS rate was 21.0% 95% CI 9.5-35.4%) and the 3-year OS rate was 23.9% 95% CI 11.7-38.2). According to the current international prognostic factor study group criteria for first relapse for the high-and very high-risk group the 2-year PFS rates were 50% and 30%, respectively. There were two treatment-related deaths from IPO, and four from HDCT. Grade 3 or 4 toxicities included neutropenia 35%), thrombocytopaenia 18%), infection 15%), diarrhoea 11%) and lethargy 8%). Conclusions IPO offers an effective, well-tolerated, non-nephrotoxic alternative to cisplatin-based salvage regimens for patients with relapsed GCTs. It appears particularly useful in high-risk patients and for those in whom cisplatin is ineffective or contra-indicated.