Multicenter phase II study of a cremophor-free polymeric micelle-formulated paclitaxel in patients (pts) with metastatic breast cancer (MBC)

Abstract

10520 Background: The results of a phase I trial of a novel taxane, a cremophor-free polymeric micelle-formulated paclitaxel (Genexol-PM), were previously reported (Clin Cancer Res 10:3708, 2004). The dose limiting toxicities were neuropathy, myalgia, and neutropenia. Notably, acute hypersensitivity reaction was not observed. Methods: This was a single arm phase II study performed at 6 major hospitals in Korea to evaluate the efficacy and safety of Genexol-PM as a 1st- or 2nd-line therapy for MBC. Genexol-PM with no premedication was given at 300 mg/m2 i.v. over 3 hr on day 1 every 3 weeks until disease progression or intolerability. Two-stage group sequential design was used. If more than 14 responses were attained in the first 30 pts, early termination was possible. Results: Forty-three pts with MBC were enrolled from 7/2004 to 12/2004. Median follow-up duration was 7.0 mo. Thirty-seven of 41 pts excluding 2 pts who did not receive Genexol-PM received Genexol-PM as a first-line therapy. Nineteen pts received prior anthracycline containing regimen in adjuvant (15) and in metastatic (4) settings. No pts were anthracycline-resistant. Median age was 48 years (range; 30 to 69 years) with ECOG PS 0 or 1. A total of 331 cycles were administered, with median of 8 per patient (range; 1 to 16). Of 39 pts evaluable for efficacy, there were 5 CRs /19 PRs with response rate of 61.5%, 13 SDs and 2 PDs. Median response duration was not reached (range; 1.9+ to 10.0+ mo). Median TTP and OS were 9.8 and 11.2 mo, respectively. G3 non-hematologic toxicities included peripheral sensory neuropathy (51.2%) and myalgia (2.4%). Hematologic toxicities were G3/G4 neutropenia (51.2%, 17.1%, respectively) and G1/2 thrombocytopenia (22.0%). Seventeen pts (41.5%) required dose reductions due to G3 neuropathy. No febrile neutropenia was observed. Eight pts developed hypersensitivity reactions with G3 in 2 pts. Mean dose intensity (DI) was 87.4 mg/m2/wk (range; 27.7 to 116.7) at 87.4% of planned DI. Conclusions: Genexol-PM at 300 mg/m2 appears a promising agent with high response rate for anthracycline sensitive MBC. Further trials at a different dose schedule or duration of delivery, or in combination with other drugs are warranted. Supported by Samyang Co, Korea. No significant financial relationships to disclose.