Recall of Herbal Supplement Highlights Gaps in Regulation

By THOMAS M. BURTON
Staff Reporter of THE WALL STREET JOURNAL March 26, 2002

Thousands of men with advanced prostate cancer are worried that the recall of an herbal supplement could cost them years off their lives.The supplement, PC-Spes , is a blend of Chinese herbs in capsule form that is often recommended by oncologists when traditional prostate-cancer treatments fail. Last month, the California Department of Health Services, working with the U.S. Food and Drug Administration, ordered a nationwide recall of PC-Spes because of possible contamination, requiring distributors to alert customers and return bottles to the manufacturer.

As many as 10,000 American men with advanced prostate cancer had been taking PC-Spes.

California health authorities ordered the recall after some bottles of PC-Spes were found to contain traces of warfarin, a prescription blood-thinning drug. State health officials say they ordered testing and analysis of the herbal product after discussions with the Orange County district attorney's office about herbal and other prostate-cancer remedies sold without prescription.

The case is a vivid illustration of gaps in the regulation of herbal products, an estimated $4.2 billion industry in the U.S. last year. The FDA oversees manufacturing of herbal supplements, requiring that they be safe and permitting limited general health claims. But unlike makers of prescription drugs, makers of supplements don't have to adhere to as rigorous manufacturing requirements or submit results of clinical trials to the FDA.

Prospective Trial of the Herbal Supplement PC-SPES in Patients With Progressive Prostate Cancer.

Small EJ, Frohlich MW, Bok R, Shinohara K, Grossfeld G, Rozenblat Z, Kelly WK, Corry M, Reese DM
J Clin Oncol 2000 Nov 1;18(21):3595-3603
University of California at San Francisco, San Francisco, CA.

Thirty-three patients with androgen-dependent prostate cancer (ADPCa) and 37 patients with androgen-independent prostate cancer (AIPCa) were treated with PC-SPES at a dose of nine capsules daily. Clinical outcome was assessed with serial serum prostate-specific androgen (PSA) level measurement and imaging studies. RESULTS: One hundred percent of ADPCa patients experienced a PSA decline of >/= 80%, with a median duration of 57+ weeks. No patient has developed PSA progression. Thirty-one patients (97%) had declines of testosterone to the anorchid range. Two ADPCa patients had positive bone scans; both improved. One patient with a bladder mass measurable on computed tomography scan experienced disappearance of this mass. Nineteen (54%) of 35 AIPCa patients had a PSA decline of >/= 50%, including eight (50%) of 16 patients who had received prior ketoconazole therapy. Median time to PSA progression was 16 weeks (range, 2 to 69+ weeks). Of 25 patients with positive bone scans, two had improvement, seven had stable disease, 11 had progressive disease, and five did not have a repeat bone scan because of PSA progression. Severe toxicities included thromboembolic events (n = 3) and allergic reactions (n = 3). Other frequent toxicities included gynecomastia/gynecodynia, leg cramps, and grade 1 or 2 diarrhea. CONCLUSION: PC-SPES seems to have activity in the treatment of both ADPCa and AIPCa and has acceptable toxicity. Further study is required to determine whether its effects exceed those expected with estrogen therapy.

N Engl J Med 1998 Sep 17;339(12):785-91

Clinical and biologic activity of an estrogenic herbal combination (PC-SPES) in prostate cancer.

DiPaola RS, Zhang H, Lambert GH, Meeker R, Licitra E, Rafi MM, Zhu BT, Spaulding H, Goodin S, Toledano MB, Hait WN, Gallo MA

Department of Medicine, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, New Brunswick 08901, USA.

BACKGROUND: Herbal mixtures are popular alternatives to demonstrated therapies. PC-SPES, a commercially available combination of eight herbs, is used as a nonestrogenic treatment for cancer of the prostate. In six of six men with prostate cancer, PC-SPES decreased serum testosterone concentrations (P<0.05), and in eight of eight patients it decreased serum concentrations of prostate-specific antigen. All eight patients had breast tenderness and loss of libido, and one had venous thrombosis. High-performance liquid chromatography, gas chromatography, and mass spectrometry showed that PC-SPES contains estrogenic organic compounds that are distinct from diethylstilbestrol, estrone, and estradiol. CONCLUSIONS: PC-SPES has potent estrogenic activity. The use of this unregulated mixture of herbs may confound the results of standard or experimental therapies and may produce clinically significant adverse effects.

Urology 1999 Aug;54(2):319-23; discussion 323-4

Use of PC-SPES, a commercially available supplement for prostate cancer, in a patient with hormone-naive disease.

Moyad MA, Pienta KJ, Montie JE

Department of Surgery, University of Michigan, Ann Arbor 48109-0330, USA.

PC-SPES, an over-the-counter supplement, is actually a combination of eight different herbs. It is being used by patients to treat cancer of the prostate at different stages of the disease and has been commercially available since November 1996. It has been observed to dramatically decrease prostate-specific antigen (PSA) values in several patients; however, its out-of-pocket cost ($162 to $486/mo) and potential side effects must be weighed against its potential objective benefits. We reviewed its use in 1 patient. METHODS: A patient with clinically localized prostate cancer (T1c) with a PSA of 8.8 ng/mL, who decided to delay any conventional treatment, began treatment with 9 PC-SPES capsules/day. RESULTS: After 3 weeks, his PSA dropped to 1.4 ng/mL and after a total of 8 weeks, his PSA was less than 0.1 ng/mL (undetectable). He has continued on a maintenance dose of 6 capsules per day, decreasing to 4 capsules per day, with a continuing undetectable PSA. During this time the patient also experienced a number of strong estrogenic effects: loss of libido, erectile dysfunction, extreme breast enlargement and tenderness, reduction in overall body hair, pitting edema, and a significant drop in his lipoprotein (a) level (from 46 to 11 mg/dL). CONCLUSIONS: PC-SPES may provide additive advantages (or disadvantages) over prescribed hormonal treatments but must be compared with other hormonal and nonhormonal treatments in clinical trials with hormone-sensitive and -insensitive patients with prostate cancer to determine its future use or nonuse.

BJU Int 2000 Mar;85(4):481-5

PC-SPES, a dietary supplement for the treatment of hormone-refractory prostate cancer.

Pfeifer BL, Pirani JF, Hamann SR, Klippel KF

Division of Urology and the Department of Anaesthesiology, University of Kentucky, Lexington, Kentucky 40536-0084, USA.

To assess the effectiveness of PC-SPES, a dietary supplement containing eight herbal extracts, which is a popular alternative therapy among patients with hormone-refractory prostate cancer; anecdotal reports claim that this agent provides relief of metastatic pain, improvements in quality of life and reduction of prostatic specific antigen (PSA) level. PATIENTS AND METHODS: Sixteen men treated for advanced metastatic prostate cancer (stage D3) with either orchidectomy or a luteinizing-hormone releasing hormone agonist, with or without anti-androgen, were enrolled into a prospective clinical trial to evaluate the possible toxic and beneficial effects of PC-SPES. After hormone-ablative therapy had failed, and with established disease progression, all patients received supplemental treatment with PC-SPES (2.88 g daily) for 5 months. Hormonal therapy was continued throughout the trial to avoid the known withdrawal effect of anti-androgen on PSA levels. RESULTS: The supplemental intake of PC-SPES was associated with significant (P<0.05-0.01) improvements in quality-of-life measures, reductions in patient's pain ratings (P<0.05-0.01), and a decline in PSA levels (P<0.01), with no major side-effects. CONCLUSIONS: These results support the anecdotal reports of the beneficial effects of PC-SPES as a comparable alternative to current management regimens in hormone-refractory prostate cancer. However, no conclusions can be drawn about the long-term effects of this new herbal therapy.

Prostate 2000 Feb 15;42(3):163-71

PC-SPES: a unique inhibitor of proliferation of prostate cancer cells in vitro and in vivo .

Kubota T, Hisatake J, Hisatake Y, Said JW, Chen SS, Holden S, Taguchi H, Koeffler HP

Division of Hematology/Oncology, Cedars-Sinai Research Institute, UCLA School of Medicine, Los Angeles, California 90048, USA.

CONCLUSIONS: PC-SPES inhibits clonal proliferation of human prostate cancer cells both in vitro and in vivo, using a murine model.