title: A phase II trial of the epothilone B analog ixabepilone (BMS-247550) in patients with metastatic melanoma.
abstract: BACKGROUND
  Ixabepilone (BMS-247550), an epothilone B analog, is a microtubule stabilizing agent which has shown activity in several different tumor types and preclinical models in melanoma. In an open label, one-arm, multi-center phase II trial the efficacy and toxicity of this epothilone was investigated in two different cohorts: chemotherapy-naïve (previously untreated) and previously treated patients with metastatic melanoma.
  
  
  RESULTS
  Eligible patients had histologically-confirmed stage IV melanoma, with an ECOG performance status of 0 to 2. Ixabepilone was administered at a dose of 20 mg/m(2) on days 1, 8, and 15 during each 28-day cycle. The primary endpoint was response rate (RR); secondary endpoints were time to progression (TTP) and toxicity. Twenty-four patients were enrolled and 23 were evaluable for response. Initial serum lactate dehydrogenase (LDH) levels were elevated in 6/11 (55%) of the previously treated and in 5/13 (38%) of the previously untreated patients. No complete or partial responses were seen in either cohort. One patient in the previously treated group developed neutropenia and fatal septic shock. Seventeen patients (8 in the previously untreated group and 9 in the previously treated group) progressed after 2 cycles, whereas six patients (3 in each group) had stable disease after 2-6 cycles. Median TTP was 1.74 months in the previously untreated group (95% CI = 1.51 months, upper limit not estimated) and 1.54 months in the previously treated group (95% CI = 1.15 months, 2.72 months). Grade 3 and/or 4 toxicities occurred in 5/11 (45%) of previously untreated and in 5/13 (38%) of previously treated patients and included neutropenia, peripheral neuropathy, fatigue, diarrhea, and dyspnea.
  
  
  CONCLUSIONS
  Ixabepilone has no meaningful activity in either chemotherapy-naïve (previously untreated) or previously treated patients with metastatic melanoma. Further investigation with ixabepilone as single agent in the treatment of melanoma is not warranted.
  
  
  BACKGROUND
  Clinical Trials.gov NCT00036764.
authors.affiliation: Department of Medical Oncology, New York University Cancer Institute, New York, New York, United States of America.
authors.forename: Patrick A
authors.initials: PA
authors.lastname: Ott
authors.forename: Anne
authors.initials: A
authors.lastname: Hamilton
authors.forename: Amanda
authors.initials: A
authors.lastname: Jones
authors.forename: Naomi
authors.initials: N
authors.lastname: Haas
authors.forename: Tsiporah
authors.initials: T
authors.lastname: Shore
authors.forename: Sandra
authors.initials: S
authors.lastname: Liddell
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Christos
authors.forename: L Austin
authors.initials: LA
authors.lastname: Doyle
authors.forename: Michael
authors.initials: M
authors.lastname: Millward
authors.forename: Franco M
authors.initials: FM
authors.lastname: Muggia
authors.forename: Anna C
authors.initials: AC
authors.lastname: Pavlick
mesh_terms: D000328:Adult; D000368:Aged; D015331:Cohort Studies; D034261:Epothilones / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000473:pathology; D008875:Middle Aged; D009362:Neoplasm Metastasis; D050257:Tubulin Modulators / Q000627:therapeutic use*
chemical_list: D034261:Epothilones; D050257:Tubulin Modulators; C430592:ixabepilone