A tolerability study of A cremophor-free albumin bound nanoparticle paclitaxel intravenously administered in patients with advanced solid tumor

BACKGROUND OBJECTIVE: Capxol is a Cremophor-free,protein stabi li zed,nanoparticle formulation of paclitaxel. This phase Ⅰstudy was designed to e valuate the tolerability/safety,toxicity profile,and maximum tolerated dose (MTD ) of Capxol administered intravenously in Chinese patients with advanced solid t umor,and to provide the recommending dose for the phase Ⅱtrial. METHOD: Capxol was administered intravenously over 30 minutes,no premedication was required. Do ses of Capxol ranged from 135 to 350 mg/m2. The treatment was repeated at 3 week s interval. RESULTS: 22 patients were treated with Capxol and totally 94 treatme nts cycles were completed. No acute hypersensitivity reactions were observed dur ing the infusion period. The treatment was tolerated well. Most of AEs (95%) we re grade 1/2; ≥grade 3 AEs were only 5%. The most common toxicities were mild leucopenia and peripheral sensory neuropathy. The dose-limiting toxicities,whic h occurred at dose level of 350 mg/m2,were grade 4 neutropenia (1 out of 3 patie nts) and grade 3 diplopia (1 out of 3 patients). The MTD was thus determined at 300 mg/m2. 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%. CONCLUSION: This phase Ⅰtrial has demonstrated that Capxol has several advantages on clinical applicat ion,which include non-premedication required,shorter infusion time,higher pacli taxel MTD and safer toxicity. The results support for that a phase Ⅱclinical tr ial to further evaluate the antitumor activity of this drug in Chinese patients is worthy. The recommended dose for phase Ⅱclinical trial is 260 mg/m2,I.V. ove r 30 minutes,and treatment repeats at every 3 weeks.