Prospective, multicenter, randomized phase II trial of the herbal supplement, PC-SPES, and diethylstilbestrol in patients with androgen-independent prostate cancer.
OBJECTIVE
To evaluate the herbal combination, PC-SPES, and diethylstilbestrol (DES) in patients with androgen independent prostate cancer (AIPC).


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 The study closed prematurely after PC-SPES was withdrawn from the market.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.


CONCLUSIONS
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.
Oh
William K
WK
Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Kantoff
Philip W
PW
Weinberg
Vivian
V
Jones
Graham
G
Rini
Brian I
BI
Derynck
Mika K
MK
Bok
Robert
R
Smith
Matthew R
MR
Bubley
Glenn J
GJ
Rosen
Robert T
RT
DiPaola
Robert S
RS
Small
Eric J
EJ
D000284:Administration, Oral; D000368:Aged; D000369:Aged, 80 and over; D000728:Androgens / Q000494:pharmacology; D000925:Anticoagulants / Q000008:administration & dosage; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology / Q000627:therapeutic use*; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D000529:Complementary Therapies / Q000592:standards; D018592:Cross-Over Studies; D004054:Diethylstilbestrol / Q000494:pharmacology / Q000627:therapeutic use*; D018450:Disease Progression; D004340:Drug Contamination; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D045166:Estradiol Congeners / Q000032:analysis; D004997:Ethinyl Estradiol / Q000032:analysis; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011471:Prostatic Neoplasms / Q000188:drug therapy*; D015203:Reproducibility of Results; D016896:Treatment Outcome; D014859:Warfarin / Q000008:administration & dosage
D000728:Androgens; D000925:Anticoagulants; D018931:Antineoplastic Agents, Hormonal; D000972:Antineoplastic Agents, Phytogenic; D004365:Drugs, Chinese Herbal; D045166:Estradiol Congeners; C114209:herbal preparation PC-SPES; D004997:Ethinyl Estradiol; D014859:Warfarin; D004054:Diethylstilbestrol