Phase II clinical trial of the epothilone B analog, ixabepilone, in patients with non small-cell lung cancer whose tumors have failed first-line platinum-based chemotherapy.
OBJECTIVE
Ixabepilone is the first in a new class of antineoplastic agents, the epothilones and their analogs. This international, randomized, phase II trial assessed two administration schedules of ixabepilone as second-line therapy in patients with non-small-cell lung cancer (NSCLC).


METHODS
Patients had experienced disease progression after one prior cisplatin- or carboplatin-based chemotherapy regimen. Ixabepilone was administered as a single 32 mg/m(2) 3-hour infusion (77 patients; arm A) or a 6 mg/m(2) 1-hour infusion daily for 5 consecutive days (69 patients; arm B) in a 3-week cycle.


RESULTS
The intent-to-treat objective response rate was 14.3% in arm A and 11.6% in arm B. Median duration of response was 8.7 months (95% CI, 5.3 to 9.5 months) in arm A and 9.6 months (95% CI, 6.1 to 19.7 months) in arm B. Median time to progression was 2.1 months (95% CI, 1.4 to 2.8 months) for arm A and 1.5 months (95% CI, 1.4 to 2.8 months) for arm B. Median survival was 8.3 months (95% CI, 5.8 to 11.5 months) for arm A, and 7.3 months (95% CI, 5.7 to 11.7 months) for arm B; the 1-year survival rate (both cohorts) was 38%. Responses occurred in patients with taxane-pretreated and platinum-refractory tumors. Both regimens had an acceptable toxicity profile. Myelosuppression was manageable, manifesting primarily as neutropenia and leukopenia. Neuropathy was primarily sensory, generally mild to moderate in severity, and mostly reversible (both regimens).


CONCLUSIONS
Single-agent ixabepilone had clinically relevant activity and an acceptable safety profile in patients with advanced NSCLC whose tumors had failed one prior platinum-based chemotherapy regimen.
Vansteenkiste
Johan
J
Respiratory Oncology Unit, University Hospital Gasthuisberg, Leuven, Belgium. johan.vansteenkiste@uz.kuleuven.ac.be
Lara
Primo N
PN
Le Chevalier
Thierry
T
Breton
Jean-Luc
JL
Bonomi
Philip
P
Sandler
Alan B
AB
Socinski
Mark A
MA
Delbaldo
Catherine
C
McHenry
Brent
B
Lebwohl
David
D
Peck
Ronald
R
Edelman
Martin J
MJ
Edelman
Mark
M
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D018450:Disease Progression; D034261:Epothilones / Q000737:chemistry* / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D017671:Platinum Compounds / Q000494:pharmacology*; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D034261:Epothilones; D017671:Platinum Compounds; C430592:ixabepilone; C093788:epothilone B