Finasteride and flutamide therapy in patients with advanced prostate cancer: response to subsequent castration and long-term follow-up

Urology. 2003 Jul;62(1):99-104. doi: 10.1016/s0090-4295(03)00145-6.

Abstract

Objectives: To report the efficacy of castration after progression on finasteride and flutamide. Standard androgen deprivation strategies for prostate cancer typically lead to castrate levels of testosterone. One alternative is the use of finasteride and flutamide.

Methods: A Phase II trial evaluated the combination of finasteride (5 mg/day) and flutamide (250 mg three times daily) in patients with rising prostate-specific antigen levels after local treatment for prostate cancer or with newly discovered metastatic disease. Patients were followed up for subsequent events, including castration-free, androgen-independent prostate cancer (AIPC)-free, and overall survival.

Results: With a median follow-up of 88 months, 5 patients (25%) continued on finasteride and flutamide, and 12 had stopped this combination and subsequently underwent medical or surgical castration. No patients experienced a flutamide withdrawal effect. All patients experienced more than a 50% decline in prostate-specific antigen after castration (mean 89%). The median protocol treatment failure-free survival was 29.9 months, the median castration-free survival was 37 months, and the median AIPC-free survival was 48.6 months. At 5 years, the overall survival rate was 65% (95% confidence interval 47% to 90%); 29% were alive and have not required castration, and 35% were alive and free of AIPC.

Conclusions: Finasteride and flutamide have a durable effect in suppressing prostate-specific antigen progression in some men with advanced prostate cancer. Furthermore, castration induces secondary responses that may be of shorter duration than if started initially, although the overall period of hormonally responsive prostate cancer is more than 4 years.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase II
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / drug therapy*
  • Adenocarcinoma / mortality
  • Adenocarcinoma / secondary
  • Adenocarcinoma / surgery
  • Adult
  • Aged
  • Androgen Antagonists / administration & dosage
  • Androgens*
  • Antineoplastic Agents, Hormonal / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Biomarkers, Tumor / blood
  • Bone Neoplasms / secondary
  • Disease Progression
  • Drug Resistance, Neoplasm
  • Enzyme Inhibitors / administration & dosage
  • Finasteride / administration & dosage
  • Flutamide / administration & dosage
  • Follow-Up Studies
  • Humans
  • Male
  • Middle Aged
  • Neoplasms, Hormone-Dependent / drug therapy*
  • Neoplasms, Hormone-Dependent / surgery
  • Orchiectomy*
  • Prostate-Specific Antigen / blood
  • Prostatic Neoplasms / drug therapy*
  • Prostatic Neoplasms / mortality
  • Prostatic Neoplasms / surgery
  • Salvage Therapy*
  • Survival Rate
  • Treatment Outcome

Substances

  • Androgen Antagonists
  • Androgens
  • Antineoplastic Agents, Hormonal
  • Biomarkers, Tumor
  • Enzyme Inhibitors
  • Finasteride
  • Flutamide
  • Prostate-Specific Antigen