Phase II clinical trial of ixabepilone (BMS-247550), an epothilone B analog, in patients with taxane-resistant metastatic breast cancer.
OBJECTIVE
Ixabepilone (BMS-247550) is an epothilone analog that optimizes the properties of naturally occurring epothilone B. Natural epothilones and their analogs promote tumor cell death by binding to tubulin and stabilizing microtubules, causing apoptosis. This international phase II trial assessed the activity of ixabepilone in patients with metastatic breast cancer (MBC) that was resistant to taxane therapy.


METHODS
MBC patients, who had experienced disease progression while receiving or within 4 months of taxane therapy (6 months if adjuvant taxane only), and who had a taxane as their last regimen, received ixabepilone (1- or 3-hour infusion of 50 mg/m(2) or 3-hour infusion of 40 mg/m(2) every 3 weeks).


RESULTS
Of 49 patients treated with 40 mg/m(2) ixabepilone during 3 hours, 35 (73%) had experienced disease progression within 1 month of their last taxane dose. The response rate was 12% (95% CI, 4.7% to 26.5%). All responses (n = 6) were partial; five of six patients had not responded to prior taxane therapy. In responders, the median response duration was 10.4 months. In 20 patients (41%), stable disease was the best outcome. Median time to progression was 2.2 months (95% CI, 1.4 to 3.2 months); median survival was 7.9 months. For treated patients across all cohorts (intent-to-treat population), the response rate was also 12% (eight of 66). Treatment-related adverse events in the study were manageable and primarily grade 1/2. Treatment-related neuropathy was mostly sensory and mild to moderate.


CONCLUSIONS
Ixabepilone (40 mg/m(2) as a 3-hour infusion every 3 weeks) demonstrates promising antitumor activity and an acceptable safety profile in patients with taxane-resistant MBC.
Thomas
Eva
E
The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA. est5151@yahoo.com
Tabernero
Josep
J
Fornier
Monica
M
Conté
Pierfranco
P
Fumoleau
Pierre
P
Lluch
Ana
A
Vahdat
Linda T
LT
Bunnell
Craig A
CA
Burris
Howard A
HA
Viens
Patrice
P
Baselga
José
J
Rivera
Edgardo
E
Guarneri
Valentina
V
Poulart
Valerie
V
Klimovsky
Judith
J
Lebwohl
David
D
Martin
Miguel
M
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D018450:Disease Progression; D004334:Drug Administration Schedule; D019008:Drug Resistance, Neoplasm; D034261:Epothilones / Q000737:chemistry* / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008875:Middle Aged; D009362:Neoplasm Metastasis; D043823:Taxoids / Q000494:pharmacology*
D000970:Antineoplastic Agents; D034261:Epothilones; D043823:Taxoids; C430592:ixabepilone; C093788:epothilone B