694P - Sequential high-dose-chemotherapy with 4 cycles paclitaxel, ifosfamide, carboplatin, etoposide (P-ICE) in relapsed/refractory male germ cell cancer: Final results with 15.8 years follow-up

Background

4 cycles of combination chemotherapy (CTx) with High-dose P-ICE plus stem-cell support is a highly active salvage chemotherapy as shown in 37 patients (pts) with relapsed/refractory germ cell tumors (Proc ASCO 2017 #4552). Final survival data after long term follow-up are now available.

Methods

From 04/08 to 05/15 37 pts were included in this phase-II trial. Eligibility criteria: relapse or progression under one or more induction CTx, ECOG PS (0-1), Creatinine-clearance > 30ml/min, adequate liver function, measurable tumor or at least marker-elevation. Dosing & schedule: Stem cell apharesis after 1 (-2) cycles induction CTx with standard dose P-ICE (Paclitaxel 135mg/m² d1, Ifosfamide 1500mg/m² d1,2,3, Carboplatin 150mg/m² d1,2,3, Etoposide 150mg/m² d1,2,3), followed by 4 sequential cycles of High-dose P-ICE (Paclitaxel 200mg/m² d1, Ifosfamide 3300mg/m² d1,2,3, Carboplatin 330mg/m² d1,2,3, Etoposide 330mg/m² d1,2,3) plus stem cell support at d5.

Results

37 patients received standard dose induction CTx, followed by high dose CTx in 33 evaluable patients (insufficient stem cell apharesis 3 pts; medical reasons 1 pt): Seminoma (5 pts) / non-seminoma (28 pts); gonadal (27 pts) / extragonadal (6 pts); N prior CTx: 1 (26 pts) / 2 (4 pts) / 3 (3 pts); ECOG-PS: 0 (19 pts) / 1 (14 pts). Response rate: CR/NED 17 (51.5%), CR/NED/PR-/SD- with marker normalization 21 (63.6%), PD 12 (36.4%). PFS all pts: 85 (4-180) months; DFS of CR/NED: 130 (58-180) months; RFS of all favourable response: 122 (23-180) months. OS all pts: 85 (6-180) months, OS favorable response: 122 (23–180) months, unfavourable response: 14 (6-28) months. Toxicity was tolerable without unexspected toxicities or treatment related death, with grade 4 hematological toxicity in all patients, 27% grade 3-4 mucositis, 12% grade 3-4 diarrhea as most common toxicities.

Conclusions

This protocol is highly active, well tolerated and seems to be currently the most appropriate regimen for salvage CTx in advanced germ cell cancer and strongly requires further prospective investigation in this patient population.

Clinical trial identification

EudraCT 2006-00600411.

Editorial acknowledgement

Legal entity responsible for the study

Martin-Luther-Universität Halle-Wittenberg.

Funding

Amgen GmbH.

Disclosure

All authors have declared no conflicts of interest.