title: Pilot study of epothilone B analog (BMS-247550) and estramustine phosphate in patients with progressive metastatic prostate cancer following castration.
abstract: BACKGROUND
  Several trials have demonstrated that the response proportions to microtubule agents in patients with prostate cancer are increased by the addition of estramustine phosphate (EMP). The epothilone B analog BMS-247550 is a novel microtubule agent that has shown activity in taxane-resistant tumors. We conducted a dose-escalation study to determine a safe dose of BMS-247550 to combine with EMP in patients with metastatic prostate cancer.
  
  
  METHODS
  Chemotherapy-naive patients with castrate-metastatic prostate cancer were treated with intravenous BMS-247550 and oral EMP (280 mg three times daily for 5 days) every 3 weeks.
  
  
  RESULTS
  Thirteen patients were treated at two dose levels (35 and 40 mg/m(2)). Three of six patients treated at 40 mg/m(2) developed grade 4 neutropenia, establishing 35 mg/m(2) as the maximum-tolerated dose. Significant peripheral neuropathy (grade >/= 2) was related to dose level and infusion rate. A decline in prostate-specific antigen (PSA) of >/= 50% was seen in 11 of 12 evaluable patients (92%) (95% confidence interval 76% to 100%). There were objective responses in soft tissue (57%) and bone metastasis (40%).
  
  
  CONCLUSIONS
  The phase II dose of BMS-247550 combined with EMP is 35 mg/m(2) over 3 h every 3 weeks. This combination is safe and >/= 50% post-therapy declines in PSA were seen in 11 of 12 patients (92%).
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000556:secondary; D000328:Adult; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology*; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology*; D001859:Bone Neoplasms / Q000556:secondary; D002369:Castration; D004305:Dose-Response Relationship, Drug; D034261:Epothilones / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology*; D004961:Estramustine / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology*; D006801:Humans; D008297:Male; D020714:Maximum Tolerated Dose; D008870:Microtubules / Q000187:drug effects; D008875:Middle Aged; D017430:Prostate-Specific Antigen / Q000032:analysis; D011471:Prostatic Neoplasms / Q000188:drug therapy*; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D018931:Antineoplastic Agents, Hormonal; D034261:Epothilones; D004961:Estramustine; D017430:Prostate-Specific Antigen; C430592:ixabepilone; C093788:epothilone B