Maintenance of clinical efficacy after dose reduction of ixabepilone plus capecitabine in patients with anthracycline- and taxane-resistant metastatic breast cancer: a retrospective analysis of pooled data from 2 phase III randomized clinical trials.
BACKGROUND
This retrospective analysis aimed to determine whether early dose reduction impacts the efficacy of ixabepilone plus capecitabine in women with metastatic breast cancer (MBC).


METHODS
In 2 phase III trials, patients (N = 1973) with anthracycline/taxane-pretreated MBC were randomized to receive ixabepilone 40 mg/m(2) on day 1 plus capecitabine 1000 mg/m(2) twice daily (BID) on days 1 to 14 or single-agent capecitabine 1250 mg/m(2) BID on days 1 to 14 of a 3-week course. Because of the similar design and populations, data from trials were pooled to evaluate efficacy of the combination regimen among women who did or did not undergo ixabepilone dose reduction during the first 4 courses. To adjust for bias resulting from selecting patients with inherently better outcome based on longer treatment durations, these analyses were restricted to patients who received ≥ 4 courses of ixabepilone.


RESULTS
The pooled cohort included 566 patients with measurable disease who were evaluable for efficacy. Patients who had early dose reduction showed similar objective response rates (ORRs) and progression-free survival (PFS) as did those with no/late dose reduction. ORRs were 62.6% (95% confidence interval [CI], 55.8%-69.0%) and 55.3% (95% CI, 49.9%-60.6%), respectively; median PFS was 7.2 months (95% CI, 6.6-8.0) and 7.0 months (95% CI, 6.5-7.5), respectively (hazard ratio = 0.98; 95% CI, 0.83-1.17).


CONCLUSIONS
These data suggest that early ixabepilone dose reduction did not affect the overall efficacy of ixabepilone plus capecitabine in patients with MBC who received ≥ 4 courses of treatment. By making appropriate dose reductions, ixabepilone-related toxicities can be minimized while maintaining clinical efficacy.
The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA. vvalero@mdanderson.org
Vicente
V
Valero
Eduard
E
Vrdoljak
Binghe
B
Xu
Eva
E
Thomas
Henry
H
Gómez
Alexey
A
Manikhas
Carlos
C
Medina
Rubi Khaw
RK
Li
Jungsil
J
Ro
Linda
L
Bosserman
Linda
L
Vahdat
Pralay
P
Mukhopadhyay
Diane
D
Opatt
Joseph A
JA
Sparano
D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D000069287:Capecitabine; D015331:Cohort Studies; D016001:Confidence Intervals; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm; D034261:Epothilones / Q000008:administration & dosage; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000031:analogs & derivatives; D006801:Humans; D008875:Middle Aged; D009362:Neoplasm Metastasis; D016017:Odds Ratio; D015996:Survival Rate; D043823:Taxoids / Q000008:administration & dosage; D016896:Treatment Outcome; D050257:Tubulin Modulators / Q000008:administration & dosage
D034261:Epothilones; D043823:Taxoids; D050257:Tubulin Modulators; D003841:Deoxycytidine; D000069287:Capecitabine; C430592:ixabepilone; D005472:Fluorouracil