title: Phase II randomized trial of weekly and every-3-week ixabepilone in metastatic breast cancer patients.
abstract: This multicenter, open-label, randomized phase II trial compared the efficacy and tolerability of weekly ixabepilone versus the standard 3 weekly dosing regimen. Patients with human epidermal growth factor receptor 2-negative, metastatic breast cancer (MBC) were randomly assigned to receive either ixabepilone 16 mg/m(2) as a 1-h intravenous (IV) infusion weekly on days 1, 8, and 15 of a 28-day cycle (1 week off therapy; n = 85), or 40 mg/m(2) as a 3-h IV infusion on day 1 of a 21-day cycle (n = 91), until disease progression or unacceptable toxicity. Randomization was stratified by (i) measurable versus nonmeasurable (evaluable) disease, (ii) ≤two versus >two prior chemotherapy regimens for MBC, and (iii) hormone receptor (HR)-positive versus HR-negative breast cancer. The primary endpoint was rate of progression-free survival (PFS) at 6 months. Of 176 randomized patients, 171 were treated. The 6-month PFS rate was significantly higher in patients treated with ixabepilone every 3 weeks (42.7, 95 % confidence interval [CI] 31.5-53.5) compared with those who received ixabepilone weekly (28.6, 95 % CI 18.9-38.9; log-rank P = 0.03). Every-3-week dosing significantly prolonged median PFS versus weekly dosing (5.3 vs. 2.9 months; log-rank P = 0.05). The every-3-week regimen was associated with higher rates of grade 3/4 toxicities, particularly neutropenia (38.2 vs. 6.1 %) and a higher rate of patient withdrawal due to adverse events. These results suggest that every-3-week ixabepilone is more effective than weekly treatment in MBC, albeit with more toxicity.
authors.affiliation: Compass Oncology, 5050 NE Hoyt Street, Suite 256, Portland, OR, 97213, USA, john.smith@usoncology.com.
authors.forename: John W
authors.initials: JW
authors.lastname: Smith
authors.forename: Svetislava
authors.initials: S
authors.lastname: Vukelja
authors.forename: Amy
authors.initials: A
authors.lastname: Rabe
authors.forename: Nicole
authors.initials: N
authors.lastname: Wentworth-Hartung
authors.forename: Nicholas
authors.initials: N
authors.lastname: Koutrelakos
authors.forename: Spencer H
authors.initials: SH
authors.lastname: Shao
authors.forename: Thomas
authors.initials: T
authors.lastname: Whittaker
authors.forename: Yunfei
authors.initials: Y
authors.lastname: Wang
authors.forename: Lina
authors.initials: L
authors.lastname: Asmar
authors.forename: Diane Opatt
authors.initials: DO
authors.lastname: McDowell
authors.forename: Pralay
authors.initials: P
authors.lastname: Mukhopadhyay
authors.forename: Joyce
authors.initials: J
authors.lastname: O'Shaughnessy
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D004334:Drug Administration Schedule; D034261:Epothilones / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D034261:Epothilones; C430592:ixabepilone