[A tolerability study of A cremophor-free albumin bound nanoparticle paclitaxel intravenously administered in...

Capxol is a Cremophor-free,protein stabilized, nanoparticle formulation of paclitaxel. This phase I study was designed to evaluate the tolerability/safety, toxicity profile, and maximum tolerated dose (MTD) of Capxol administered intravenously in Chinese patients with advanced solid tumor, and to provide the recommending dose for the phase II trial.

Capxol was administered intravenously over 30 minutes, no premedication was required. Doses of Capxol ranged from 135 to 350 mg/m(2). The treatment was repeated at 3 weeks interval.

22 patients were treated with Capxol and totally 94 treatments cycles were completed. No acute hypersensitivity reactions were observed during the infusion period. The treatment was tolerated well. Most of AEs (95%) were grade 1/2; >/= grade 3 AEs were only 5%. The most common toxicities were mild leucopenia and peripheral sensory neuropathy. The dose-limiting toxicities,which occurred at dose level of 350 mg/m(2),were grade 4 neutropenia (1 out of 3 patients) and grade 3 diplopia (1 out of 3 patients). The MTD was thus determined at 300 mg/m(2). Among 21 patients who were evaluable for efficacy, 1 CR, 7 PR, 9 SD, 4 PD were observed, overall response rate (CR+PR) was 38%.

This phase I trial has demonstrated that Capxol has several advantages on clinical application, which include non-premedication required, shorter infusion time,higher paclitaxel MTD and safer toxicity. The results support for that a phase II clinical trial to further evaluate the antitumor activity of this drug in Chinese patients is worthy. The recommended dose for phase II clinical trial is 260 mg/m(2), I.V. over 30 minutes,and treatment repeats at every 3 weeks.