Phase II clinical trial of ixabepilone (BMS-247550), an epothilone B analog, as first-line therapy in patients with metastatic breast cancer previously treated with anthracycline chemotherapy.
OBJECTIVE
There is a need for new agents to treat metastatic breast cancer (MBC) in patients for whom anthracycline therapy has failed or is contraindicated. This study was conducted to assess the efficacy and safety of the novel antineoplastic, the epothilone B analog ixabepilone, in patients with MBC previously treated with an adjuvant anthracycline.


METHODS
Patients were age >or= 18 years and had received a prior anthracycline-based regimen as adjuvant treatment. Ixabepilone as first-line metastatic chemotherapy was administered as a 40 mg/m(2) intravenous infusion during 3 hours every 3 weeks. The primary efficacy end point was objective response rate (ORR). Secondary efficacy end points included duration of response, time to response, time to progression, and survival.


RESULTS
All 65 patients were assessable for response. Their median age was 52 years (range, 33 to 80 years). ORR was 41.5% (95% CI, 29.4% to 54.4%), median duration of response was 8.2 months (95% CI, 5.7 to 10.2 months), and median time to response was 6 weeks (range, 5 to 17 weeks). Median survival was 22.0 months (95% CI, 15.6 to 27.0 months). Treatment-related adverse events were manageable and mostly grades 1/2: the most common of these (other than alopecia) was mild to moderate neuropathy, which was primarily sensory and mostly reversible in nature.


CONCLUSIONS
Ixabepilone is efficacious and has a predictable and manageable safety profile in women with MBC previously treated with an adjuvant anthracycline.
Roché
Henri
H
Institut Claudius Regaud, 20-24 rue du Saint Pierre, 31052 Toulouse Cedex, France. roche.henri@claudiusregaud.fr
Yelle
Louise
L
Cognetti
Francesco
F
Mauriac
Louis
L
Bunnell
Craig
C
Sparano
Joseph
J
Kerbrat
Pierre
P
Delord
Jean-Pierre
JP
Vahdat
Linda
L
Peck
Ronald
R
Lebwohl
David
D
Ezzeddine
Rana
R
Curé
Hervé
H
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018943:Anthracyclines / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy*; D015331:Cohort Studies; D034261:Epothilones / Q000737:chemistry* / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008875:Middle Aged; D009362:Neoplasm Metastasis; D013997:Time Factors; D016896:Treatment Outcome
D018943:Anthracyclines; D000970:Antineoplastic Agents; D034261:Epothilones; C430592:ixabepilone; C093788:epothilone B