Prospective randomized study comparing docetaxel, estramustine, and prednisone with docetaxel and prednisone in metastatic hormone-refractory prostate cancer

J Clin Oncol. 2008 Nov 10;26(32):5261-8. doi: 10.1200/JCO.2008.16.9524. Epub 2008 Sep 15.

Abstract

Purpose: To assess the efficacy and toxicity of the addition of estramustine to docetaxel (D) for the treatment of metastatic hormone-refractory prostate cancer.

Patients and methods: One hundred fifty patients were randomly assigned to D alone (35 mg/m(2) on days 2 and 9, every 3 weeks) or D in combination with estramustine (D/E; 280 mg orally three times a day on days 1 to 5 and 8 to 12, every 3 weeks). All patients received prednisone (10 mg/d). The primary end point was prostate-specific antigen (PSA) response rate, which was defined as a decrease in PSA > or = 50% from baseline. The study was powered to test the hypothesis that D/E would improve the PSA response rate by 25%.

Results: The PSA response rate was not statistically different between the two groups. PSA of less than 4 ng/mL occurred in 29 (41%) of 71 patients receiving D/E and in 17 (25%) of 69 patients receiving D (P = .05). No significant differences were found for median time to PSA progression (D/E, 6.9 months; D, 7.3 months) or median overall survival time (D/E, 19.3 months; D, 21 months). More patients had at least one grade 3 or 4 toxicity with D/E (45%) compared with D (21%; P = .005), mainly as a result of grade 3 or 4 GI toxicity (P = .05). Serious adverse events were more frequent with D/E (n = 20) than with D (n = 9; P = .04).

Conclusion: The addition of estramustine to weekly D does not provide any clinically relevant advantage. Both regimens are well tolerated, although the toxicity profile favors D without estramustine.

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / drug therapy*
  • Adenocarcinoma / immunology
  • Adenocarcinoma / mortality
  • Adenocarcinoma / pathology
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents, Hormonal / therapeutic use*
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Belgium / epidemiology
  • Disease Progression
  • Docetaxel
  • Dose-Response Relationship, Drug
  • Drug Resistance, Neoplasm*
  • Estramustine / administration & dosage
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Neoplasm Metastasis
  • Prednisone / administration & dosage
  • Prospective Studies
  • Prostate-Specific Antigen / blood
  • Prostatic Neoplasms / drug therapy*
  • Prostatic Neoplasms / immunology
  • Prostatic Neoplasms / mortality
  • Prostatic Neoplasms / pathology
  • Taxoids / administration & dosage
  • Time Factors
  • Treatment Outcome

Substances

  • Antineoplastic Agents, Hormonal
  • Taxoids
  • Docetaxel
  • Estramustine
  • Prostate-Specific Antigen
  • Prednisone