title: Ixabepilone (epothilone B analogue BMS-247550) is active in chemotherapy-naive patients with hormone-refractory prostate cancer: a Southwest Oncology Group trial S0111.
abstract: OBJECTIVE
  The epothilones are a new class of tubulin-polymerizing agents with activity in taxane-sensitive and resistant tumor models. We evaluated ixabepilone (BMS-247550) in patients with metastatic hormone-refractory prostate cancer (HRPC).
  
  
  METHODS
  Eligible patients had chemotherapy-naive metastatic HRPC, a Zubrod performance status of 0 to 2, and adequate organ function. All patients received BMS-247550 at 40 mg/m2 over 3 hours every 3 weeks. The primary end point was proportion of patients achieving a prostate-specific antigen (PSA) response.
  
  
  RESULTS
  Forty-eight patients with metastatic HRPC were registered. Forty-two patients were eligible, with a median age of 73 years and a median PSA level of 111 ng/mL; 78% had bone-only or bone and soft tissue metastases, and 88% had objective radiologic disease progression at registration. Grade 3 and 4 adverse events (AEs) occurred in 16 and three patients, respectively. All grade 4 toxicities were neutropenia or leukopenia. The most frequent grade 3 AEs were neuropathy (eight patients), hematologic toxicity (seven patients), flu-like symptoms, and infection (five patients each). There were no grade 3/4 thrombocytopenia or grade 5 AEs. There were 14 confirmed PSA responses (33%; 95% CI, 20% to 50%); 72% of PSA responders had declines greater than 80%, and two patients achieved an undetectable PSA. The estimated median progression-free survival is 6 months (95% CI, 4 to 8 months), and the median survival is 18 months (95% CI, 13 to 24 months).
  
  
  CONCLUSIONS
  Ixabepilone has demonstrated activity in patients with chemotherapy-naive metastatic HRPC. Major toxicities were neutropenia and neuropathy. Further testing to define its activity relative to standard therapy is warranted.
authors.affiliation: University of Michigan Comprehensive Cancer Center, Ann Arbor, USA. mahahuss@med.umich.edu
authors.forename: Maha
authors.initials: M
authors.lastname: Hussain
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Tangen
authors.forename: Primo N
authors.initials: PN
authors.lastname: Lara
authors.forename: Ulka N
authors.initials: UN
authors.lastname: Vaishampayan
authors.forename: Daniel P
authors.initials: DP
authors.lastname: Petrylak
authors.forename: A Dimitrios
authors.initials: AD
authors.lastname: Colevas
authors.forename: Wael A
authors.initials: WA
authors.lastname: Sakr
authors.forename: E David
authors.initials: ED
authors.lastname: Crawford
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology; D000368:Aged; D000369:Aged, 80 and over; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use; D001859:Bone Neoplasms / Q000188:drug therapy / Q000556:secondary; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm; D034261:Epothilones / Q000009:adverse effects / Q000627:therapeutic use*; D005500:Follow-Up Studies; D006402:Hematologic Diseases / Q000139:chemically induced; D006801:Humans; D008297:Male; D008875:Middle Aged; D009422:Nervous System Diseases / Q000139:chemically induced; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D012983:Soft Tissue Neoplasms / Q000188:drug therapy / Q000556:secondary; D016896:Treatment Outcome
chemical_list: D018931:Antineoplastic Agents, Hormonal; D034261:Epothilones; D017430:Prostate-Specific Antigen; C430592:ixabepilone