Note: Not to be confused with SPES (a different product) or with copycat products marketed with similar names.
Background
WARNING: THIS PRODUCT HAS BEEN RECALLED FROM THE U.S. MARKET AND SHOULD NOT BE USED.
PC-SPES® is an herbal combination product that was produced and marketed until early 2002 by BotanicLab, Inc. for the treatment of prostate cancer. The initials "PC" stand for "prostate cancer" and "spes" is Latin for hope.
Based on a Chinese herbal formula, the ingredients of PC-SPES® were officially listed as including Serenoa repens (saw palmetto) and seven other herbs: Chrysanthemummorifolium (chrysanthemum, mum, Chu-hua), Ganoderma lucidum (reishi mushroom, Ling Zhi), Glycyrrhiza glabra (licorice), Isatis indigotica Fort (Da Qing Ye, dyer's wood), Panax pseudo-ginseng (San Qi), Rabdosia rubescens (rubescens, Dong Ling Cao), and Scutellaria baicalensis (skullcap, Huang-chin).
In low quality studies, PC-SPES® was observed to reduce serum prostate specific antigen (PSA) levels, reduce evidence of metastatic disease, diminish pain, and improve quality of life in patients with prostate cancer. This evidence was viewed as promising by major U.S. cancer centers.
However, in early 2002, the U.S. Food and Drug Administration (FDA) Safety Information and Adverse Event Reporting Program issued a warning to consumers to avoid using PC-SPES® based on findings that the product contained the anticoagulant ("blood thinner") warfarin. Bleeding disorders had previously been reported with PC-SPES®. The manufacturer voluntarily recalled the product. Samples of PC-SPES® were later found to contain variable amounts of the non-steroidal anti-inflammatory drug indomethacin, the synthetic estrogen diethystilbesterol (DES), and the estrogen ethinyl estradiol.
A study published in the September 2002 issue of the Journal of the National Cancer Institute analyzed lots of PC-SPES® manufactured between 1996 and 2001. This evaluation found variable ingredients in PC-SPES® between lots, with higher levels of indomethacin and DES after 1999. These post-1999 samples were found to have much greater estrogenic properties compared to earlier samples, and to possess a higher level of activity against prostate cell lines in laboratory tests. After 2001, greater amounts of the natural constituents licochalconeA and baicalin, as well as warfarin, were found in samples. These results suggest that PC-SPES® produced at different times may not be equivalent or comparable, and that the "anti-cancer" effects of PC-SPES® may have been due to undeclared prescription drug ingredients.
Several other BotanicLab products have also been found to contain undeclared prescription drugs. It is not clear if these adulterants were present in raw materials obtained by BotanicLab from other sources or were added later in the manufacturing process.
Since BotanicLab closed its doors, several products with similar names have been introduced on the market, but none has been evaluated scientifically to the same extent as PC-SPES®. The National Center for Complementary and Alternative Medicine (NCCAM) has expressed willingness to support future research on formulations that are true to the claimed ingredients and proven not to be contaminated.
Evidence
DISCLAIMER:
These uses have been tested in humans or animals. Safety and effectiveness have not always been proven. Some of these conditions are potentially serious, and should be evaluated by a qualified healthcare provider.
Prostate cancer:
Uncontrolled human studies of PC-SPES® have reported improvements in patients with both androgen-dependentand androgen-independent prostate cancer. Overall, these studies found prostate-specificantigen (PSA) levels to fall by greater than 50% in most patients as well as improvements in bone scans and X-rays, reductions in pain scores, and improvements in quality of life. In a 2002 preliminary report (conference abstract) of a comparison between PC-SPES® and diethylstilbestrol (DES) in patients withandrogen-independent metastatic prostate cancer, patients treatedwith PC-SPES® had a greater reduction in PSAlevels. However, the later finding that undeclared amounts of DES are present in some PC-SPES® samples clouds these results.
Various explanations for the effectiveness of PC-SPES® were initially proposed. Estrogen-like effects were reported prior to 1998. These may be due to herbs with estrogen-like effects or to undeclared estrogenic drugs. The constituent baicalin, a flavone found inScutellaria baicalensis, was found in laboratory experiments to inhibit the enzymes 12-lipoxygenase,5-alpha-reductase, and aromatase. In addition, PC-SPES® extracts were reported to cause cell death (apoptosis) or to slow the growth of cancer cell lines.
The recent finding that different lots of PC-SPES® produced between 1996 and 2001 contained different ingredients from each other has raised questions about whether studies of PC-SPES® can be compared with each other. The discovery of undeclared prescription drug ingredients including the non-steroidal anti-inflammatory drug indomethacin, the synthetic estrogen diethystilbesterol (DES), the estrogen ethinyl estradiol, and the anticoagulantwarfarin, make it unclear if these constituents may have caused the observed clinical effects.
Because of these complicated circumstances, and the fact that PC-SPES® has never been compared to placebo or standard cancer treatments in a well-reported study, the question of effectiveness remains unclear.
Due to known and theoretical safety concerns, samples of PC-SPES® that may be in the possession of patients should not be used.
Grade: C
Tradition
WARNING:
DISCLAIMER:
The below uses are based on tradition, scientific theories, or limited research. They often have not been thoroughly tested in humans, and safety and effectiveness have not always been proven. Some of these conditions are potentially serious, and should be evaluated by a qualified healthcare provider. There may be other proposed uses that are not listed below.
Dosing
Adult (18 years and older)
Based on known safety concerns associated with PC-SPES®, no dosing regimen is recommended. Samples of PC-SPES® that may be in the possession of patients should not be used.
Children (younger than 18 years)
Based on known safety concerns associated with PC-SPES®, no dosing regimen is recommended. Samples of PC-SPES® that may be in the possession of patients should not be used.
Safety
DISCLAIMER:
Many complementary techniques are practiced by healthcare professionals with formal training, in accordance with the standards of national organizations. However, this is not universally the case, and adverse effects are possible. Due to limited research, in some cases only limited safety information is available.
Allergies
In one human study, allergic reactions were reported in 2% of patients and treatment was stopped in one case due to throat swelling and shortness of breath. It is not clear which ingredient in PC-SPES® might have been responsible. Products containing herbs similar to PC-SPES® should be avoided by people with allergies to any of the included herbs.
Side Effects and Warnings
PC-SPES® has been recalled and should not be used. Undeclared prescription drug ingredients have been found in samples of PC-SPES®, including indomethacin, diethystilbesterol (DES), ethinyl estradiol, and warfarin.
PC-SPES® may increase the risk of blood clots. Several cases of blood clots, including life-threatening clots to the lungs, have been reported with PC-SPES® use. In contrast, cases of bleeding have also been reported. These are theorized to be due to undeclared amounts of the prescription drug warfarin in some samples of PC-SPES®, or to the presence of the PC-SPES® ingredient saw palmetto, which is associated with one report of bleeding. This would add to the risk of bleeding in patients with bleeding disorders or taking drugs that may increase the risk of bleeding. The bleeding disorder disseminated intravascular coagulation (DIC), which can include clotting, bleeding, or both, has also been reported.
PC-SPES® has also been associated with erectile dysfunction, loss of libido, hot flashes, breast/nipple tenderness, breast enlargement, water retention (edema), and leg cramps.
Adverse effects associated with undeclared prescription drug ingredients in PC-SPES® are possible, such as gastrointestinal distress from indomethacin.
Pregnancy and Breastfeeding
PC-SPES® has not been evaluated during pregnancy or breastfeeding and should be avoided. Estrogenic-effects may be harmful. The undeclared prescription drug DES, discovered in some samples of PC-SPES®, may increase the risk of reproductive tract abnormalities in daughters born to women taking this drug.
Interactions
Interactions with Drugs
Based on reported cases of bleeding and inclusion of undeclared amounts of the prescription blood-thinner warfarin in some samples, PC-SPES® may increase the risk of bleeding when taken with drugs that increase the risk of bleeding. Some examples include aspirin, anticoagulants ("blood thinners") such as warfarin (Coumadin®) or heparin, anti-platelet drugs such as clopidogrel (Plavix®), and non-steroidal anti-inflammatory drugs such as ibuprofen (Motrin®, Advil®) or naproxen (Naprosyn®, Aleve®). In contrast, PC-SPES® has also been associated with an increased risk of blood clots, which may be due to estrogen-like effects. This would work against the action of blood-thinning medications.
Based on the proposed anti-androgenic mechanism of action of saw palmetto, a major ingredient of PC-SPES®, additive effects may occur with anti-androgen drugs such as the 5α-reductase inhibitor finasteride (Proscar®); the androgen receptor antagonists bicalutamide (Casodex®), flutamide (Eulexin®), and nilutamide (Nilandron®); or the GnRH antagonists leuprolide (Lupron®), goserelin (Zoladex®), and histrelin (Supprelin®). Similarly, this therapy may decrease the effectiveness of therapeutic androgens such as testosterone (Androderm®, Testoderm®), methyltestosterone (Android®, Testred®, Virilon®), fluoxymesterone (Halotestin®), nandrolone decanoate (Deca-Dubrolin®), or stanozolol (Winstrol®).
PC-SPES® may add to the estrogenic effects of other drugs, based on estrogen-like effects reported in studies, and the presence of undeclared amounts of prescription estrogen drugs in some samples of PC-SPES®.
PC-SPES® may interfere with certain chemotherapy drugs like paclitaxel. PC-SPES® may affect the way the liver breaks down certain drugs.
Interactions with Herbs and Dietary Supplements
Based on reported cases of bleeding and inclusion of undeclared amounts of the prescription blood-thinner warfarin in some samples, PC-SPES® may increase the risk of bleeding when taken with herbs and supplements that are believed to increase the risk of bleeding. Multiple cases of bleeding have been reported with the use of Ginkgo biloba, and fewer cases with garlic and saw palmetto. Numerous other agents may theoretically increase the risk of bleeding, although this has not been proven in most cases. In contrast, PC-SPES® has also been associated with an increased risk of blood clots, which may be due to estrogen-like effects. This would work against the action of blood-thinning agents.
PC-SPES® may add to the estrogenic effects of other agents based on estrogen-like effects reported in studies and the presence of undeclared amounts of prescription estrogen drugs in some samples.
PC-SPES® may affect the way the liver breaks down certain herbs and supplements.
Attribution
This information is based on a systematic review of scientific literature, and has been edited and peer-reviewed by contributors to the Natural Standard Research Collaboration (www.naturalstandard.com): Dawn Costa, BA, BS (Natural Standard Research Collaboration); Shaina Tanguay-Colucci, BS (Natural Standard Research Collaboration); Catherine Ulbricht, PharmD (Massachusetts General Hospital); Wendy Weissner, BA (Natural Standard Research Collaboration).
Bibliography
DISCLAIMER:
Natural Standard developed the above evidence-based information based on a thorough systematic review of the available scientific articles. For comprehensive information about alternative and complementary therapies on the professional level, go to www.naturalstandard.com. Selected references are listed below.
de la TA, Buttyan R, Hayek O, et al. Herbal therapy PC-SPES: in vitro effects and evaluation of its efficacy in 69 patients with prostate cancer. J Urol 2000;164(4):1229-1234.
DiPaola RS, Zhang H, Lambert GH, et al. Clinical and biologic activity of an estrogenic herbal combination (PC- SPES) in prostate cancer. N Engl J Med 1998;339(12):785-791.
Oh WK, George DJ, Hackmann K, et al. Activity of the herbal combination, PC-SPES, in the treatment of patients with androgen-independent prostate cancer. Urology 2001;57(1):122-126.
Oh WK, Kantoff PW, Weinberg V, et al. Prospective, multicenter, randomized phase II trial of the herbal supplement, PC-SPES, and diethylstilbestrol in patients with androgen-independent prostate cancer. J Clin Oncol 2004;22(18):3705-3712.
Pfeifer BL, Pirani JF, Hamann SR, et al. PC-SPES, a dietary supplement for the treatment of hormone-refractory prostate cancer. BJU Int 2000;85(4):481-485.
Small EJ, Frohlich MW, Bok R, et al. Prospective trial of the herbal supplement PC-SPES in patients with progressive prostate cancer. J Clin Oncol 2000;18(21):3595-3603.
Sovak M, Seligson AL, Konas M, et al. Herbal composition PC-SPES for management of prostate cancer: identification of active principles. J Natl Cancer Inst 2002;94(17):1275-1281.
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