title: 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.
abstract: 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.
authors.affiliation: Respiratory Oncology Unit, University Hospital Gasthuisberg, Leuven, Belgium. johan.vansteenkiste@uz.kuleuven.ac.be
authors.forename: Johan
authors.initials: J
authors.lastname: Vansteenkiste
authors.forename: Primo N
authors.initials: PN
authors.lastname: Lara
authors.forename: Thierry
authors.initials: T
authors.lastname: Le Chevalier
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Breton
authors.forename: Philip
authors.initials: P
authors.lastname: Bonomi
authors.forename: Alan B
authors.initials: AB
authors.lastname: Sandler
authors.forename: Mark A
authors.initials: MA
authors.lastname: Socinski
authors.forename: Catherine
authors.initials: C
authors.lastname: Delbaldo
authors.forename: Brent
authors.initials: B
authors.lastname: McHenry
authors.forename: David
authors.initials: D
authors.lastname: Lebwohl
authors.forename: Ronald
authors.initials: R
authors.lastname: Peck
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Edelman
authors.forename: Mark
authors.initials: M
authors.lastname: Edelman
mesh_terms: 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
chemical_list: D000970:Antineoplastic Agents; D034261:Epothilones; D017671:Platinum Compounds; C430592:ixabepilone; C093788:epothilone B