Ixabepilone Plus Capecitabine for Metastatic Breast Cancer Progressing After Anthracycline and Taxane Treatment

作者：Eva S. Thomas, Henry Gómez, Rubi K. Li, Hyun Cheol Chung, Luis Enrique Fein, Valorie F. Chan, Jacek Jassem, Xavier B. Pivot, Judith Klimovsky, F Mendoza, Binghe Xu, Mario Campone, Guillermo Luis Lerzo, Ronald A. Peck, Pralay Mukhopadhyay, Linda T. Vahdat, Henri Hubert Roche · 发表于：Journal of Clinical Oncology · 年份：2007 · DOI：10.1200/jco.2007.12.6557 · 被引用次数：483 · 研究领域：Cancer Treatment and Pharmacology、Breast Cancer Treatment Studies、Chemotherapy-related skin toxicity

PURPOSE: Effective treatment options for patients with metastatic breast cancer resistant to anthracyclines and taxanes are limited. Ixabepilone has single-agent activity in these patients and has demonstrated synergy with capecitabine in this setting. This study was designed to compare ixabepilone plus capecitabine versus capecitabine alone in anthracycline-pretreated or -resistant and taxane-resistant locally advanced or metastatic breast cancer. PATIENTS AND METHODS: Seven hundred fifty-two patients were randomly assigned to ixabepilone 40 mg/m(2) intravenously on day 1 of a 21-day cycle plus capecitabine 2,000 mg/m(2) orally on days 1 through 14 of a 21-day cycle, or capecitabine alone 2,500 mg/m(2) on the same schedule, in this international phase III study. The primary end point was progression-free survival evaluated by blinded independent review. RESULTS: Ixabepilone plus capecitabine prolonged progression-free survival relative to capecitabine (median, 5.8 v 4.2 months), with a 25% reduction in the estimated risk of disease progression (hazard ratio, 0.75; 95% CI, 0.64 to 0.88; P = .0003). Objective response rate was also increased (35% v 14%; P < .0001). Grade 3/4 treatment-related sensory neuropathy (21% v 0%), fatigue (9% v 3%), and neutropenia (68% v 11%) were more frequent with combination therapy, as was the rate of death as a result of toxicity (3% v 1%, with patients with liver dysfunction [>/= grade 2 liver function tests] at greater risk). Capecitabine-rela...