title: Evaluation of epothilone B analog in advanced soft tissue sarcoma: a phase II study of the phase II consortium.
abstract: OBJECTIVE
  Epothilones are a new class of nontaxane tubulin polymerization agents that have activity in taxane-resistant tumors. Epothilone B (BMS-247550) is a semisynthetic analog of the natural product epothilone B. This study was performed to determine the activity of BMS-247550 in patients with soft tissue sarcomas (STSs) who had not received prior chemotherapy for metastatic disease.
  
  
  METHODS
  Patients with measurable, advanced, or metastatic STS with no prior chemotherapy for metastatic disease were treated with BMS-2457550 50 mg/m(2) intravenously during 1 hour every 21 days. All responses were confirmed 4 weeks later.
  
  
  RESULTS
  Thirty-one patients (median age, 54 years; range, 19 to 78 years; 48% female) were entered onto the trial and were assessable for response. All but one patient had an Eastern Cooperative Oncology Group performance score of 0% or 1%, and 39% had received prior adjuvant chemotherapy. Mean follow-up was 22 months, with a confirmed response rate of 6% (95% CI, 0% to 17%). Median time to progression was 4.5 months (95% CI, 1.9 to 8.3 months), and 1 year progression-free survival was 17% (95% CI, 8% to 38%). Median survival was 16.4 months, with a 1-year survival of 61% (95% CI, 46% to 81%). Toxicity was mainly hematologic, with eight of 31 (26%) patients experiencing grade 3 to 4 leukopenia; 15 of 31 patients (48%) experienced grade 3 to 4 neutropenia. The grade 3 to 4 nonhematologic toxicities included neuropathies (26%), myalgia (13%), and fatigue (10%).
  
  
  CONCLUSIONS
  BMS-247550 has limited activity against STSs when given in this dose and schedule. The clinical toxicity is similar to that of taxanes.
authors.affiliation: Mayo Clinic College of Medicine, 200 First St, Southwest, Medical Oncology, Rochester, MN 55905, USA. okuno.scott@mayo.edu
authors.forename: Scott
authors.initials: S
authors.lastname: Okuno
authors.forename: William J
authors.initials: WJ
authors.lastname: Maples
authors.forename: Michelle R
authors.initials: MR
authors.lastname: Mahoney
authors.forename: Tom
authors.initials: T
authors.lastname: Fitch
authors.forename: James
authors.initials: J
authors.lastname: Stewart
authors.forename: Paula M
authors.initials: PM
authors.lastname: Fracasso
authors.forename: Michael
authors.initials: M
authors.lastname: Kraut
authors.forename: David S
authors.initials: DS
authors.lastname: Ettinger
authors.forename: Fitzroy
authors.initials: F
authors.lastname: Dawkins
authors.forename: Charles
authors.initials: C
authors.lastname: Erlichman
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D018450:Disease Progression; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D034261:Epothilones / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D012509:Sarcoma / Q000188:drug therapy*; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D034261:Epothilones; C093788:epothilone B