Ixabepilone plus capecitabine for metastatic breast cancer progressing after anthracycline and taxane treatment.
OBJECTIVE
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.


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-related toxicities were similar for both treatment groups.


CONCLUSIONS
Ixabepilone plus capecitabine demonstrates superior efficacy to capecitabine alone in patients with metastatic breast cancer pretreated or resistant to anthracyclines and resistant to taxanes.
Thomas
Eva S
ES
M.D. Anderson Cancer Center, Houston, TX, USA. eva.s.thomas@kp.org
Gomez
Henry L
HL
Li
Rubi K
RK
Chung
Hyun-Cheol
HC
Fein
Luis E
LE
Chan
Valorie F
VF
Jassem
Jacek
J
Pivot
Xavier B
XB
Klimovsky
Judith V
JV
de Mendoza
Fernando Hurtado
FH
Xu
Binghe
B
Campone
Mario
M
Lerzo
Guillermo L
GL
Peck
Ronald A
RA
Mukhopadhyay
Pralay
P
Vahdat
Linda T
LT
Roché
Henri H
HH
D000328:Adult; D000368:Aged; D018943:Anthracyclines / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality; D001952:Bridged-Ring Compounds / Q000627:therapeutic use; D000069287:Capecitabine; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D018450:Disease Progression; D034261:Epothilones / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D006801:Humans; D008875:Middle Aged; D009362:Neoplasm Metastasis; D043823:Taxoids / Q000627:therapeutic use
D018943:Anthracyclines; D001952:Bridged-Ring Compounds; D034261:Epothilones; D043823:Taxoids; D003841:Deoxycytidine; C080625:taxane; D000069287:Capecitabine; C430592:ixabepilone; D005472:Fluorouracil