Phase I/II study of paclitaxel plus ifosfamide (TI) followed by high-dose paclitaxel, ifosfamide, and carboplatin (TIC) with autologous stem cell transplant (ASCT) for salvage treatment of germ cell tumors (GCT).

4534 Background: High-dose chemotherapy (HDCT) can achieve durable remissions in 30-60% of GCT patients (pts) requiring salvage treatment. This Phase I/II study investigated safety and efficacy of a novel high-dose regimen (TI-TIC) in this population. Methods: Pts age ≥18 with GCT and progression after ≥1 cisplatin-based regimen were eligible. TI-TIC consists of 1-2 cycles of conventional-dose paclitaxel plus ifosfamide (TI) q14-21 days followed by 3 cycles of high-dose TIC with ASCT q21-28 days. TI dosing was constant. In Phase I, high-dose TIC was administered in 1 of 5 cohorts (I: 6, 8 or 10g/m2; T: 200 or 250mg/m2; C: AUC=21 or 24) using a standard 3+3 dose escalation design to determine the maximal tolerated dose (MTD). In Phase II, Simon’s 2-stage optimal design was used to estimate the complete response (CR) rate at MTD. Results: Of 26 pts (25 male; median age 31; 21 nonseminoma, 5 seminoma) enrolled, 23 received ≥1 cycle of high-dose TIC. Primary sites included testis (n=15), mediastinum (n=6), ot...