Bottom Line: PC-SPES has been taken off the market due to contamination. Clinical trials showed that PC-SPES lowered PSA levels, but there was no evidence that it could shrink prostate tumors or prolong survival in cancer patients.
PC-SPES contains eight herbs (reishi mushroom, baikal skullcap, rabdosia, dyer's woad, chrysanthemum, saw palmetto, panax ginseng, and licorice.) Scientists do not know which substances in PC-SPES account for its activity. No single botanical or chemical extract appears responsible for the overall effects of this product. Laboratory tests have analyzed the makeup of PC-SPES and have identified estrogen-like compounds that suppress growth and proliferation of human tumor cell lines on contact, including breast, colon, hormone-dependent prostate and hormone-independent prostrate. PC-SPES appears to interfere with the process of tumor cell division and also causes tumor cell death (apoptosis) when cells are exposed to it long enough. The ability of PC-SPES to kill cancer cells may be due to alteration of expression of specific genes involved in regulating the cell cycle, cell structure and response to androgens (such as testosterone). This effect has not been confirmed in humans. PC-SPES has been found to contain small amount of prescription drugs, including diethylstiberstrol and ethinyl estradiol. It is unclear whether these agents account for PC-SPES anticancer effects.
To treat prostate cancer Several clinical trials showed that PC-SPES could lower PSA levels, but none showed that it could shrink prostate tumors or prolong survival in men with prostate cancer. PC-SPES is currently not available in the U.S. because of contamination.
Cancer treatment A phase II study looked at the effect of PC-SPES in 33 patients with hormone-dependent and 37 patients with hormone-independent prostate cancer. Patients received nine capsules of PC-SPES daily. All patients with hormone-dependent cancer had a decline in PSA levels of greater than or equal to 80% and most saw their testosterone levels drop significantly. PSA levels dropped by at least half in 19 patients with hormone-independent tumors. Although drops in PSA levels is a good sign, the fact that only three patients had tumor shrinkage indicates that this is not an effective cancer therapy. Three patients developed blood clots and three had allergic reactions to PC-SPES. Leg cramps, diarrhea, and breast growth were other side effects.
In another study of 69 prostate cancer patients taking PC-SPES, blood PSA levels dropped in 82% of patients at two months, in 78% of patients at six months, and in 88% of patients at 12 months. Side effects included many cases of nipple tenderness in and one case of phlebitis (vein inflammation). Again, although a PSA drop is a good sign, it is more important if the tumors shrink, which was not addressed in this study.
Sixteen men previously treated for advanced metastatic prostate cancer who had not responded to hormonal therapy took three capsules of PC-SPES three times a day for 20 weeks. Fourteen of these men also underwent other therapies, including LHRH-agonist, anti-androgens, and removal of the testes. After treatment, patients reported a significant improvement in quality of life and had over a 50% reduction in PSA levels. Eight men reported breast tenderness. However, the researchers do not report if patients experienced progression of disease.
A survey was carried out of UsToo members and other prostate cancer patients taking PC-SPES. Out of 82 patients, beneficial effects were reported in 77%, the other 23% reporting more limited or marginal results. Reductions in PSA were reported and were sustained for the duration PC-SPES therapy, approaching 2 years in some cases. However, tumor shrinkage was not reported.
PC-SPES was recalled and its production was halted in February 2002 because of product contamination with the prescription drugs warfarin, alprazolam, and diethylstilbestrol. It is not clear when or if production will resume.
PC-SPES must be used within a treatment plan developed between the patient and oncologist.
PC-SPES should not be confused with SPES, a different product sold by BotanicLab, which is an immunostimulant that contains 15 botanicals. SPES was also recalled for contamination in February 2002.
This product is regulated by the FDA as a dietary supplement. Unlike approved drugs, supplements are not required to be manufactured under specific standardized conditions. This product may not contain the labeled amount or may be contaminated. In addition, it may not have been tested for safety or effectiveness.
You have a history of uncontrolled high blood pressure, unstable angina, deep venous thrombosis, coagulopathies (clotting disorders), biliary colic or untreated gall stones (PC-SPES may aggravate these conditions).
You are taking other herbal and dietary supplements. All other herbal and dietary supplements (including grapefruit juice) should be discontinued while using PC-SPES. Use of prescription medications should be avoided as well, since PC-SPES may increase their levels in the blood, which may result in toxicity.
You are taking medicine to lower your blood pressure (PC-SPES may lessen their effect).
You are taking corticosteroids (PC-SPES may have an additive effect).
You use diuretics (PC-SPES may lessen their effect).
You are taking digoxin (PC-SPES may increase the risk of cardiac toxicity because of loss of potassium).
You take monoamine oxidase inhibitors (MAOIs) (PC-SPES may increase their effect).
You are on hormone therapy (PC-SPES may alter your response to hormones because of its possible estrogenic effects).
Rare: Pulmonary embolism (blood clot in the lungs), deep vein thrombosis (blood clot), phlebitis (inflammation of a vein), edema (swelling), and allergic reactions.
Case report: Retroperitoneal hemorrhage (bleeding from the lining of the abdominal cavity).
PC-SPES is a natural product consisting of eight herbs: reishi mushroom, baikal skullcap, rabdosia, dyer's woad, chrysanthemum, saw palmetto, panax ginseng, and licorice. Patients use this supplement to treat prostate cancer. Published studies document efficacy of PC-SPES (10)(14)(15)(16). In vitro testing reveals suppression of human tumor cell lines, including androgen-sensitive and -insensitive prostate cancer (7)(12). Use of PC-SPES brings about significant decreases in androgen and PSA levels in humans. It is thought that PC-SPES contains phytoestrogens (17) and other undefined components that contribute to its activity. Recent concerns about product contamination with DES, warfarin, and alprazolam resulted in a voluntary recall by Botanic Labs, the manufacturer of PC-SPES. This product is not available in U.S. at this time.
The active components of PC-SPES are unknown. Laboratory analysis of PC-SPES by HPLC, gas chromatography, and mass spectrometry indicate the presence of estrogenic organic compounds different from diethylstilbestrol(DES), estrone, and estradiol. In vitro testing of this extract shows suppressed cell proliferation and reduced clonogenicity in human tumor cell lines, including prostrate, breast, and colon. The predominant cell cycle effect induced by PC-SPES is prolongation of G1 phase; however, apoptosis was observed after exposure of tumor cells to PC-SPES for 48 hours or longer. PC-SPES also inhibits proliferation of LNCaP prostate cell lines, associated with a 60-70% down regulation of the proliferating cell nuclear antigen. Preliminary studies evaluating the viability of prostate cancer cell lines LNCaP, LNCaP apoptosis-resistant derivative, LNCaP-bcl-2, PC3, and DU145 at three concentrations of PC-SPES show inhibited growth at concentrations of 4 mcg/ml or less. Another recent in vitro study indicates its cytotoxicity may be due to alteration of expression of specific genes involved in regulating the cell cycle, cell structure and androgen response. No single botanical or chemical extract appears responsible for the overall effects of this product. PC-SPES has been found to contain small amount of diethylstiberstrol and ethinyl estradiol. It is unclear whether these agents account for PC-SPES anticancer effects. (2)(3)(4)(5)(6)(7)(12)(13)(14)(16)
Recent concerns about product contamination with prescription drugs, such as DES, warfarin, and alprazolam resulted in a voluntary recall by Botanic Labs, the manufacturer of PC-SPES. This product is not available in U.S. at this time. PC-SPES should not be confused with SPES, a different product sold by BotanicLab, which is an immunostimulant that contains 15 botanicals. SPES was also recalled for contamination on February 8, 2002.
Patients with history of uncontrolled hypertension, unstable angina, deep venous thrombosis, coagulopathies, history of biliary colic or untreated cholelithiasis should not take PC-SPES.
All herbal and dietary supplements should be discontinued while using PC-SPES. Avoid concomitant use of all medications. Antihypertensives: PC-SPES may antagonize the effect of antihypertensives. Corticosteroids: PC-SPES may potentiate the effect of steroids. Diuretics: PC-SPES may antagonize the effect of diuretics. Digoxin: PC-SPES may increase the risk of cardiac toxicity due to loss of potassium. Monoamine oxidase inhibitors (MAOIs): PC-SPES may increase the effects of MAOIs. Hormones: PC-SPES may alter response due to possible estrogenic activity. CYP450: PC-SPES may inhibit the 3A4 enzyme, thereby increasing levels of drugs metabolized by CYP450 3A4. Grapefruit Juice: Grapefruit juice may increase the mineralocorticoid activities of the licorice component due to inhibition of CYP450 3A4. (11)
Small EJ, et al. Prospective trial of the herbal supplement PC-SPES in patients with progressive prostate cancer. J Clin Oncol 2000;18:3595-603. A prospective phase II study to assess the efficacy and toxicity of PC-SPES in androgen- dependent or -independent prostate cancer. Thirty-three patients with androgen-dependent prostate cancer (ADPCa) and 37 patients with androgen-independent (AIPCa) were treated with PC-SPES at a dose of nine capsules daily. Clinical outcomes were assessed with serial serum prostate-specific androgen (PSA) level measurement and imaging studies. One hundred percent of ADPCa patients experienced a PSA decline of >/=80%, with a median duration of 57+ weeks. No patient developed PSA progression. In 31 patients (97%), testosterone levels dropped to the anorchid range. Two ADPCa patients had positive bone scans; both improved. One patient with a bladder mass measurable on CT scan experienced disappearance of this mass. Nineteen (54%) of 35 AIPCa patients had a PSA decline of >/=50%, including eight (50%) of l6 patients who had received prior ketoconazole therapy. Severe toxicities included thromboembolic events (n=3) and allergic reactions (n=3). Other frequent toxicities included gynecomastia, leg cramps, and grade 1 or 2 diarrhea.
Pfeifer BL, et al. PC-SPES, a dietary supplement for the treatment of hormone-refractory prostate cancer. BJU Int 2000;85:481-5. Sixteen men previously treated for advanced metastatic prostate cancer (stage D3) who were refractory to hormonal therapy, had 3 consecutive months of increasing PSA, and progression of disease by MRI or CT scan were enrolled. Fourteen patients received concurrent therapy with LHRH-agonist ± anti-androgen and 2 received orchiectomy. Patients were given three capsules of PC-SPES three times a day for 20 weeks. The trial assessed toxicity and response to PC-SPES. Following 20 weeks of treatment there was a significant improvement in QOL parameters and greater than 50% reduction in PSA levels. Adverse events were reported and included breast tenderness in 8 patients and one report of dyspepsia. The author reports a decline in the number of bone lesions and pelvic lymphadenopathy, but this data is not delineated. No information regarding progression of disease is provided.
Porterfield H. Survey of UsToo members and other prostate cancer patients to evaluate the efficacy and safety of PC-SPES. Mol Urol 1999;3:333-6. A survey of UsToo members and other prostate cancer patients was conducted to evaluate the safety and efficacy of PC-SPES. Out of 82 patients, beneficial effects were reported in 77% of the respondents, the other 23% reporting more limited or marginal results. Reductions in PSA, as much as 70 ng/ml, were reported and were sustained for the duration PC-SPES therapy, approaching 2 years in some cases. No significant adverse effects were reported.
DiPaola R, et al. Clinical and biologic activity of an estrogenic herbal combination (PC-SPES) in prostate cancer. N Engl J Med 1998;339:785-91. The estrogenic activity of PC-SPES was measured by means of transcriptional-activation assays in yeast and a biologic assay in mice. The clinical activity of PC-SPES was assessed in eight patients with hormone-sensitive prostate cancer by measuring serum prostate-specific antigen and testosterone concentrations during and after treatment. The yeast assays showed an estrogenic activity similar to estradiol. In six of six men with prostate cancer, PC-SPES decreased serum testosterone concentrations, 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 and gas chromatography and mass spectrometry showed that PC-SPES contains estrogen organic compounds that are distinct from diethylstilbestrol, estrone, and estradiol.
