Anticancer effect of combination therapy of VP16 and fosfesterol in hormone-refractory prostate cancer

Am J Clin Oncol. 2008 Apr;31(2):188-94. doi: 10.1097/COC.0b013e3181595af6.

Abstract

Objectives: We conducted the present study to evaluate the safety profile and therapeutic value of a combination of etoposide and fosfestrol for treatment of hormone-refractory prostate cancer (HRPC).

Methods: Forty patients with HRPC were included in the study. The median age was 71 years (range, 50-86 years), the Gleason's score ranged from 5 to 10, and the median prostate-specific antigen level was 62.6 ng/mL (range, 4.738-30789 ng/mL). The patients received oral etoposide 25 mg/d and fosfestrol 300 mg/d.

Results: The response rate in terms of measurable disease, serum prostate-specific antigen level, and overall evaluation was 36.8% (CR: 18.4%; PR: 18.4%), 80% (CR: 55%; PR: 25%), and 40% (CR: 20%; PR: 20%) with a median duration of response of 13.6, 13.5, and 13.5 months, respectively. An objective clinical response for overall evaluation was shown by 90% (CR: 20%; PR: 20%; SD: 50%) of the patients, with a median response duration of 15.7 months; 16 patients (40%) are currently alive without recurrence after a median follow-up period of 21.2 months. The overall survival and progression-free survival was 30.5% and 28.8% at 40 months, respectively. No grade III toxicities occurred in any of the patients. Serial measurements in 34 patients using the Functional Assessment of Cancer Therapy-Prostate showed a significant improvement in quality of life as a result of the therapy.

Conclusions: The combination of oral etoposide and fosfestrol is active in patients with HRPC. The regimen is tolerable and has a significant impact on quality of life as measured by the Functional Assessment of Cancer Therapy-Prostate in a limited sample of patients.

MeSH terms

  • Adenocarcinoma / drug therapy*
  • Adenocarcinoma / pathology
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Diethylstilbestrol / administration & dosage
  • Diethylstilbestrol / adverse effects
  • Diethylstilbestrol / analogs & derivatives
  • Drug Resistance, Neoplasm
  • Drug-Related Side Effects and Adverse Reactions
  • Etoposide / administration & dosage
  • Etoposide / adverse effects
  • Humans
  • Male
  • Middle Aged
  • Prostate-Specific Antigen / blood
  • Prostate-Specific Antigen / drug effects
  • Prostatic Neoplasms / drug therapy*
  • Prostatic Neoplasms / pathology
  • Quality of Life
  • Salvage Therapy
  • Survival Analysis

Substances

  • Etoposide
  • Diethylstilbestrol
  • fosfestrol
  • Prostate-Specific Antigen