title: A phase II trial of trastuzumab plus weekly ixabepilone   and carboplatin in patients with HER2-positive metastatic breast   cancer: an Eastern Cooperative Oncology Group Trial.
abstract: The epothilone B analogue, ixabepilone, binds to b-tubulin, is effective for taxane-refractory metastatic breast cancer (MBC), and may be given every 3 weeks or weekly. We evaluated the efficacy of weekly ixabepilone (I) plus trastuzumab (T) and carboplatin (C) as first line therapy in HER2 + MBC. Patients with HER2+ (3+ by IHC or FISH amplified) MBC received I (15 mg/m2 IV) and C (area under the curve, AUC = 2 IV) on days 1, 8, and 15 of a 28-day cycle for a maximum of 6 cycles, plus weekly T (4 mg/kg loading dose then 2 mg/kg IV) during chemotherapy then every 3 weeks (6 mg/kg IV) until disease progression. The primary objective was to determine whether the combination was associated with a response rate (RR) of at least 75%. Fifty-nine patients were treated, and 39 had HER2 overexpression confirmed in a central lab (cHER2+). For all treated patients, objective response occurred in 26 patients (44%; 95% CI 31-58%), median time to progression was 8.2 months (95% CI 6.3-9.9), and median overall survival was 34.7 months (95% CI 25.7 to [not reached]). Results were comparable for cHer2? cancers. Grade 3-4 adverse events included neutropenia (49%), thrombocytopenia (14%), fatigue (12%), nausea (7%), diarrhea (7%), and neuropathy (7%). One patient died from treatment complications during cycle 1. Weekly ixabepilone and carboplatin plus trastuzumab have an acceptable toxicity profile, but are not likely to be associated with an RR of 75% in HER2+ MBC. Efficacy appears comparable to paclitaxel, carboplatin, and trastuzumab.
authors.affiliation: Breast Medical Oncology, The University of Texas M. D. Anderson Cancer Center, 1155 Pressler Street,Unit 1354, P.O. Box 301438, Houston, TX 77030, USA. smoulder@mdanderson.org
authors.forename: Stacy
authors.initials: S
authors.lastname: Moulder
authors.forename: Hailun
authors.initials: H
authors.lastname: Li
authors.forename: Molin
authors.initials: M
authors.lastname: Wang
authors.forename: William J
authors.initials: WJ
authors.lastname: Gradishar
authors.forename: Edith A
authors.initials: EA
authors.lastname: Perez
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Sparano
authors.forename: Michael
authors.initials: M
authors.lastname: Pins
authors.forename: Ximing
authors.initials: X
authors.lastname: Yang
authors.forename: George W
authors.initials: GW
authors.lastname: Sledge
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D016190:Carboplatin / Q000008:administration & dosage / Q000009:adverse effects; D034261:Epothilones / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D016190:Carboplatin; D034261:Epothilones; D018719:Erb-b2 Receptor Tyrosine Kinases; C430592:ixabepilone