Treatability of patients with metastatic breast cancer after treatment by ixabepilone in first-line

Abstract

e12030 Background: Ixabepilone (BMS-247550), an epothilone B analog, was an active drug in metastatic breast cancer (MBC) patients who were anthracycline pretreated. The main toxicity was mild to moderate neuropathy which was primarily sensory and mostly reversible. This study was performed to evaluate retrospectively the treatability of patients after discontinuation of ixabepilone given as first metastatic line in 2 institutions. Methods: From February 2001 to December 2002, 50 patients (median age 54 years) were enrolled in a phase II clinical trial evaluating ixabepilone as first line chemotherapy (CT) in MBC. Fifteen patients were treated by 50 mg/m2 (as a 1-hour infusion subsequently amended as a 3-hour infusion), and 34 received ixabepilone at 40 mg/m2 IV infusion during 3 hours every 3 weeks in response to the early safety findings. Neurotoxicity occurred in 38 patients (76%) leading to treatment discontinuation in 19 patients (38%). The description of subsequent treatments after ixabepilone was realized to detect eventual cross resistance and subsequent neurotoxicity. Results: Patients received a median number of 3 subsequent CT (range, 0–11) whatever the ixabepilone dosage. The median duration of subsequent CT lines after ixabepilone was of 3.6 months (range, 0–15.6 months). Patients who developed neurotoxicity received a median of 3 subsequents CT (range, 0–9), and those who did not, received a median of 1.5 subsequent lines. Forty-four patients received a second metastatic CT with different regimens stratified according the main cytotoxic agents, which were capecitabine in 54.5% of patients, taxane in 18.2%, and vinorelbine in 15.9%. At third line of metastatic CT (n = 37), taxane based regimen, capecitabine based regimen, and vinorelbine based regimen were administered respectively in 45.9%, 16.2%, and 13.5%. Median survival from first administration of ixabepilone was of 25.3 months (range, 0.2–89.2 months). After ixabepilone treatment, best response rate of subsequent CT was of 18.4%, and neurotoxicity was observed in 42.1%. Conclusions: In spite of neurotoxicity development with ixabepilone used as first metastatic line, the administration of subsequent lines of CT for treated MBC, especially with taxane based regimen, was normally possible. No significant financial relationships to disclose.