title: Paclitaxel, estramustine phosphate, and carboplatin in patients with advanced prostate cancer.
abstract: OBJECTIVE
  To determine the safety and activity of weekly paclitaxel in combination with estramustine and carboplatin (TEC) in patients with advanced prostate cancer.
  
  
  METHODS
  In a dose-escalation study, patients with advanced prostate cancer were administered paclitaxel (weekly 1-hour infusions of 60 to 100 mg/m(2)), oral estramustine (10 mg/kg), and carboplatin (area under the curve, 6 mg/mL-min every 4 weeks). Paclitaxel levels were determined 0, 30, 60, 90, and 120 minutes and 18 hours after infusion, and a concentration-time curve was estimated. Once a safe dose was established, a multi-institutional phase II trial was conducted in patients with progressive androgen-independent disease.
  
  
  RESULTS
  Fifty-six patients with progressive androgen-independent disease were treated for a median of four cycles. The dose of paclitaxel was escalated from 60 to 100 mg/m(2) without the occurrence of DLT. Posttherapy decreases in serum prostate-specific antigen levels of 50%, 80%, and 90% were seen in 67%, 48%, and 39% (95% confidence interval, 55% to 79%, 35% to 61%, 26% to 52%) of the patients, respectively. Of the 33 patients with measurable disease, two (6%) had a complete response and 13 (39%) had a partial response. The overall median time to progression was 21 weeks, and the median survival time for all patients was 19.9 months. Major grade 3 or 4 adverse effects were thromboembolic disease (in 25% of patients), hyperglycemia (in 38%), and hypophosphatemia (in 42%). Significant leukopenia, thrombocytopenia, and peripheral neuropathy were not observed.
  
  
  CONCLUSIONS
  TEC has significant antitumor activity and is well tolerated in patients with progressive androgen-independent prostate cancer.
authors.affiliation: Genitourinary Oncology Service, Division of Solid Tumor, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY 10021-6007, USA. kellyw@mskcc.org
authors.forename: W K
authors.initials: WK
authors.lastname: Kelly
authors.forename: T
authors.initials: T
authors.lastname: Curley
authors.forename: S
authors.initials: S
authors.lastname: Slovin
authors.forename: G
authors.initials: G
authors.lastname: Heller
authors.forename: J
authors.initials: J
authors.lastname: McCaffrey
authors.forename: D
authors.initials: D
authors.lastname: Bajorin
authors.forename: A
authors.initials: A
authors.lastname: Ciolino
authors.forename: K
authors.initials: K
authors.lastname: Regan
authors.forename: M
authors.initials: M
authors.lastname: Schwartz
authors.forename: P
authors.initials: P
authors.lastname: Kantoff
authors.forename: D
authors.initials: D
authors.lastname: George
authors.forename: W
authors.initials: W
authors.lastname: Oh
authors.forename: M
authors.initials: M
authors.lastname: Smith
authors.forename: D
authors.initials: D
authors.lastname: Kaufman
authors.forename: E J
authors.initials: EJ
authors.lastname: Small
authors.forename: L
authors.initials: L
authors.lastname: Schwartz
authors.forename: S
authors.initials: S
authors.lastname: Larson
authors.forename: W
authors.initials: W
authors.lastname: Tong
authors.forename: H
authors.initials: H
authors.lastname: Scher
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D004961:Estramustine / Q000008:administration & dosage; D006801:Humans; D008297:Male; D008875:Middle Aged; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy; D017239:Paclitaxel / Q000008:administration & dosage; D017430:Prostate-Specific Antigen / Q000097:blood / Q000187:drug effects; D011471:Prostatic Neoplasms / Q000188:drug therapy*; D015996:Survival Rate
chemical_list: D004961:Estramustine; D016190:Carboplatin; D017430:Prostate-Specific Antigen; D017239:Paclitaxel