Phase I study of satraplatin and docetaxel in solid malignancies

Abstract

2570 Background: Satraplatin (S) is a novel, orally administered platinum compound with broad antitumor activity. Preclincal studies have shown synergy with docetaxel (TAX). Here we report the results of a phase I study of S with TAX with and without G-CSF support in patients with advanced solid tumors. Methods: Patients with metastatic solid malignancies were enrolled. All pts had an ECOG performance status of < 2, adequate hematologic, renal and liver function. Prior chemotherapy/XRT had to have been completed 4 weeks prior to enrollment. Other exclusion criteria included prior XRT to > 30% of the marrow, neuropathy grade > 1, and previous platinum or TAX chemotherapy within 3 months of enrollment. TAX was given as a 1-hour infusion on day 1 (starting dose 60 mg/m2) in combination with S (starting dose 50 mg/m2/day, rounded to nearest 10 mg) administered orally in the fasted state, days 1–5 of a 21-day cycle. Results: 23 patients with a median of 3 prior cytotoxic chemotherapy regimens were enrolled. At dose level 1, 2/7 patients developed grade 3/4 neutropenia lasting > 5 days, exceeding the MTD. At dose level-1 (TAX 60 mg/m2, S 40 mg/m2/d), 1/6 patients developed grade 3/4 ANC. The protocol was subsequently amended to re-escalate with G-CSF (300 mcg SQ days 6–15) support. With G-CSF support, no DLT was observed and further dose escalation to level 2 (TAX 70 mg/m2, S 50 mg/m2/d) resulted in only 1/6 patients developing significant neutropenia. The most commonly reported adverse event was neutropenia (22%), followed by anemia, diarrhea and fatigue. Conclusions: The S and TAX combination is feasible with neutropenia as the main toxicity. Of note, this was a heavily pretreated cancer population. The recommended phase II dose is TAX 60 mg/m2 IV day 1 with SA 40 mg/m2 PO days 1–5, without G-CSF, and TAX 70 mg/m2 IV day 1 with SA 50 mg/m2 PO days 1–5, with G-CSF support, repeated in 3-week cycles. Preliminary data shows encouraging activity in men with high-grade castrate-refractory prostate cancer. As a result, this combination is currently being explored in an expanded cohort assessing the safety/tolerability/efficacy in men with chemo-naive, castrate-refractory prostate cancer. No significant financial relationships to disclose.