A phase II study to determine if sensory neuropathy of nab-paclitaxel can be reduced by prolonging infusion in patients with non-small cell lung cancer (NSCLC)

Abstract

18087 Background: We have previously reported that nab-paclitaxel (ABI-007; Abraxane) administered at 125 mg/m 2 over 30 minutes on days 1, 8, and 15 every 28 days has a response rate (RR) of 30% and median survival of 11 months [Rizvi, Proc. ASCO 2006]. We also observed 15/40 (38%) patients developed grade 2/3 sensory neuropathy with a 30 minute infusion. We hypothesize that a longer infusion with nab-paclitaxel may reduce peak plasma levels and accordingly reduce sensory neuropathy. Methods: After enrollment of 40 patients at 125 mg/m 2 over 30 minutes on days 1, 8, and 15 every 28 days, we amended the protocol to study an additional 25 patients with chemotherapy naïve stage IV NSCLC with a 2 hour infusion. The enrollment criteria and treatment schedule otherwise remained the same. Our goal was to detect 1 to 2 grade improvement of peripheral neuropathy with 80% power at the two sided p=0.10 significance level compared to the 40 patients treated with this dose given over 30 minutes. Results: To date, 22 of 25 planned patients have been treated with a 2 hour infusion. The mean number of doses administered was 11 for the initial 40 patients treated with a 30 minute infusion and 10 for the 22 patients treated with the 2 hour infusion. We observed 9/40 grade 2 and 6/40 grade 3 sensory neuropathy with the 30 minute infusion and 2/22 grade 2 and 1/22 grade 3 sensory neuropathy with the 2 hour infusion. The combined grade 2 and 3 toxicities were less with the 2 hour infusion (3/22, 14%) compared with the 30 minute infusion (15/40, 38%; p=0.078, Fisher’s exact test). Conclusions: Prolonging the infusion rate of nab-paclitaxel from 30 minutes to 2 hours is associated with a significant decrease in grade 2 and 3 sensory neuropathy. Efficacy data is presently being evaluated. [Table: see text]