title: Dose escalation of oral vinorelbine in combination with estramustine in hormone-refractory adenocarcinoma of the prostate.
abstract: BACKGROUND
  The primary objective of the current study was to identify the tolerable dose level of oral vinorelbine when given in combination with estramustine to men with hormone-refractory prostate cancer (HRPC). The secondary objectives were to describe the toxicities of the combined regimen in patients with HRPC and to estimate the efficacy of oral vinorelbine in combination with estramustine based on the prostate-specific antigen (PSA) response.
  
  
  METHODS
  Thirty-three patients with HRPC were treated on a 28-day cycle with estramustine at a dose of 140 mg orally 3 times a day on Days 1-3 and 8-10. Vinorelbine was given orally on Days 2 and 9. The initial dose of vinorelbine was 50 mg/m2 and was escalated to 70 mg/m2 using the time-to-event continual reassessment method.
  
  
  RESULTS
  Three of 17 patients experienced dose-limiting toxicity at the 70 mg/m2 dose level of oral vinorelbine. One patient experienced dose-limiting toxicity at a dose of 60 mg/m2 and no dose-limitig toxicities were reported at the 50 mg/m2 dose. The overall response rate by > or = 50% reduction in PSA was 17.2%, (95% confidence interval, 5.9-35.8%).
  
  
  CONCLUSIONS
  Oral vinorelbine at doses of 70 mg/m2 may be safely combined with estramustine. The combination appears to have modest activity in men with advanced prostate cancer. The trial design employed the time-to-event continual reassessment method, which potentially allows for rapid accrual, a more complete assessment of toxicities, and a larger fraction of patients to be treated at an effective dose. More active regimens are needed to further evaluate the utility of this clinical trial design in patients with prostate cancer.
authors.affiliation: Division of Hematology/Oncology, Department of Internal Medicine, University of Michigan School of Medicine, Ann Arbor, Michigan 48109, USA.
authors.forename: Niklas J
authors.initials: NJ
authors.lastname: Mackler
authors.forename: Rodney L
authors.initials: RL
authors.lastname: Dunn
authors.forename: Beth
authors.initials: B
authors.lastname: Hellerstedt
authors.forename: Kathleen A
authors.initials: KA
authors.lastname: Cooney
authors.forename: Judith
authors.initials: J
authors.lastname: Fardig
authors.forename: Karin
authors.initials: K
authors.lastname: Olson
authors.forename: Kenneth J
authors.initials: KJ
authors.lastname: Pienta
authors.forename: David C
authors.initials: DC
authors.lastname: Smith
mesh_terms: D000230:Adenocarcinoma / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D000284:Administration, Oral; D000368:Aged; D000369:Aged, 80 and over; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use*; D016001:Confidence Intervals; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm; D004359:Drug Therapy, Combination; D004961:Estramustine / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D006801:Humans; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D014747:Vinblastine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000077235:Vinorelbine
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D004961:Estramustine; D014747:Vinblastine; D017430:Prostate-Specific Antigen; D000077235:Vinorelbine