Prospective, multicenter, randomized phase II trial of the herbal supplement, PC-SPES, and diethylstilbestrol in patients with androgen-independent prostate cancer.

Abstract

PURPOSE:

To evaluate the herbal combination, PC-SPES, and diethylstilbestrol (DES) in patients with androgen independent prostate cancer (AIPC).

PATIENTS AND METHODS:

A randomized phase II study was conducted with cross-over design. Patients were randomly assigned to receive either three PC-SPES capsules orally three times a day or DES 3 mg orally once a day. Prophylactic warfarin was administered. At clinical or prostate-specific antigen progression, patients received the other therapy. The study closed prematurely after PC-SPES was withdrawn from the market. Chemical analyses were performed on multiple lots of PC-SPES.

RESULTS:

Ninety patients were enrolled, of whom 85 were assessable for response. Prostate-specific antigen declines > or = 50% were noted in 40% (95% CI, 25% to 56%) with PC-SPES, and 24% (95% CI, 12% to 39%) with DES. Median response duration was not reached with PC-SPES, and was 3.8 months with DES. Median time to progression for randomly assigned patients was 5.5 months for PC-SPES and 2.9 months for DES. Common toxicities included mild fatigue, gynecomastia, and mastodynia. Five thromboembolic events occurred (one PC-SPES, four DES). Responses in the cross-over phase were inconclusive. Four lots of PC-SPES had measurable quantities of DES, ranging from 0.01% to 3.1% of the dose used in the DES arm. Ethinyl estradiol was also detected in PC-SPES lots.

CONCLUSION:

PC-SPES and DES demonstrate activity in AIPC and are well tolerated. However, the synthetic estrogens, DES and ethinyl estradiol, were detected in various lots of PC-SPES, including those used in this trial. Clinical trials that utilize herbal therapies must account for issues of purity and consistency.

• Authors: William K Oh, Philip W Kantoff, Vivian Weinberg, Graham Jones, Brian I Rini, Mika K Derynck, Robert Bok, Matthew R Smith, Glenn J Bubley, Robert T Rosen, Robert S DiPaola, Eric J Small
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 22 Issue 18 Pg. 3705-12 (Sep 15 2004) ISSN: 0732-183X [Print] United States
• PMID: 15289492 (Publication Type: Clinical Trial, Clinical Trial, Phase II, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Androgens
• Anticoagulants
• Antineoplastic Agents, Hormonal
• Antineoplastic Agents, Phytogenic
• Drugs, Chinese Herbal
• Estradiol Congeners
• herbal preparation PC-SPES
• Ethinyl Estradiol
• Warfarin
• Diethylstilbestrol

Topics

• Administration, Oral
• Aged
• Aged, 80 and over
• Androgens (pharmacology)
• Anticoagulants (administration & dosage)
• Antineoplastic Agents, Hormonal (pharmacology, therapeutic use)
• Antineoplastic Agents, Phytogenic (chemistry, pharmacology, therapeutic use)
• Complementary Therapies (standards)
• Cross-Over Studies
• Diethylstilbestrol (pharmacology, therapeutic use)
• Disease Progression
• Drug Contamination
• Drugs, Chinese Herbal (chemistry, pharmacology, therapeutic use)
• Estradiol Congeners (analysis)
• Ethinyl Estradiol (analysis)
• Humans
• Male
• Middle Aged
• Prospective Studies
• Prostatic Neoplasms (drug therapy)
• Reproducibility of Results
• Treatment Outcome
• Warfarin (administration & dosage)