Description
PC-SPES, PC-HOPE, PC-CARE and PC-PLUS are herbal supplements which have been marketed for the promoted for prostate health and treatment of prostate cancer. PC-SPES, the original product consisting of a combination of eight herbs, is no longer available. It was recalled by the US Food and Drug Administration (FDA) in 2002 due to concerns over quality control and reported contamination with prescription drugs. Newer products including similar herbs produced under improved conditions to avoid contamination include PC-HOPE, PC-CARE and PC-PLUS.
Efficacy
Prostate-specific antigen (PSA) levels: Limited data available from case reports and observational or preliminary studies report an overall significant decrease in prostate-specific antigen levels (PSA). However, the above-mentioned contamination issues render these results meaningless. An improved PC-Spes2 preparation was evaluated in an uncontrolled study which did not confirm the encouraging results.
Safety
There are several risks associated with PC-SPES in addition to the contamination of PC-SPES with synthetic drugs. Adverse events are common and even severe reactions are on record. Products claiming to be PC-SPES replacements without quality control exist.
Citation
Wider B, Mora D, CAM Cancer Collaboration. PC-SPES [online document], Nov 9, 2023.
Document history
Assessed as up to date by Dana Mora in November 2023. Revised by Barbara Wider in February 2023. Assessed as up to date in August 2020, January 2019, February 2017, January 2015, August 2013 by Barbara Wider. Summary first published in January 2012, authored by Liene Dhooghe. Next update due: November 2026.
Description and background
PC-SPES stands for prostate cancer (PC) and spes, which is the Latin word for hope. It was a patented dietary supplement, manufactured by BotanicLab, Brea, California, USA and commercially available from 1996 to 2002. It was recalled by the US Food and Drugs Administration (FDA) in 2002 due to contamination with prescription drugs. (Blumenthal 2002; Sovak 2002). Although it was withdrawn from the market, it remains accessible through internet order4. Other similar products claim to be the replacement supplement for PC-SPES, for example PC-HOPE, PC-CARE and PC-PLUS. However, often different combinations of plants are used.
Ingredients and quality issues
The original PC-SPES capsules contained 320 mg of eight Chinese herbs: 25.6 mg Dendranthema morifolium or Chrysanthemum morifolium flower; 32.0 mg Isatis tinctoria or Isatis indigotica leaf (dyer’s woad or glastum); 3.2 mg Glycyrrhiza uralensis root (Chinese liquorice, not to be mistaken with Glycyrrhiza glabrum); 99.2 mg Ganoderma lucidum stem (also known as Lingzhi or Reishi mushroom); 25.6 mg Panax pseudoginseng root (not to be mistaken with Panax ginseng); 35.2 mg Rabdosia rubescens or Isodon rubescens leaf; 19.2 mg Serenoa repens berry (saw palmetto); and 51.2 mg Scutellaria baicalensis or Scutellaria laterifolia root (Baikal skullcap). (Lee 2005)
PC-SPES was withdrawn from the market due to concerns over quality control and reported contamination with traces of warfarin, indomethacin and diethylstilbesterol. (Blumenthal 2002; Sovak 2002)
Alleged indications
PC-SPES was commercialized for prostate health and strengthening of the immune system. Research focused on investigating its efficacy in androgen-independent and androgen-dependent prostate cancer.
Application and dosage
The preparations are administered as tablets or capsules. There is no medically approved dose, only recommendations from the manufacturers.
Mechanism of action
Because of the combination of several plant extracts, multiple mechanisms of action can be responsible for the claimed anticancer activity. Most of the agents have shown in vitro activity, ranging from stimulation of natural killer-cell activity to growth inhibition of different cell lines. (Kosty 2004) There are components that show estrogenic activity or inhibit 5-alpha reductase. (Kosty 2004) The extracts can induce apoptosis and can suppress cell growth by restricting cell cycle progression at G(1)/S phase. (Yip 2003; Marks 2002)
Legal issues
Although the original product was withdrawn from the market in 2002, similar products are available from health food shops or online.
Only limited clinical data are available of PC-SPES in prostate cancer. Many publications are case reports or observational studies but no randomized controlled trials (RCTs) have been conducted. (Meyer 2002) A crossover study was teminated because of observed contamination of PC-SPES with several prescription drugs. (Walsh 2005)
Description of studies
Prostate-specific antigen (PSA) levels
Early observational and preliminary studies with PC-SPES reported a remarkable reduction in PSA levels (DiPaola 1998) and a significant improvement in quality of life and reduction in pain ratings. (Pfeifer 2000) Several case reports were published, reporting a substantial decrease in serum prostate-specific antigen (PSA) levels following a regular use of PC-SPES. (de la Taille 2000b; Olaku 2011; Lock 2001; Oh 2002; Moyad 1999)
Several phase II studies in patients with androgen-insensitive prostate cancer observed an overall decline in PSA of at least 50%. (de la Taille 1999; de la Taille 2000a; Small 2000; Oh 2001)
In a phase II RCT with crossover design, comparing PC-SPES to diethylstilbestrol, the analysis of the used PC-SPES product showed, however, quantities of diethylstilbestrol and ethinyl estradiol (Oh 2004; Guns 2002) Warfarin and indomethacin were also detected, which led to the study being terminated. (Ko 2003) The presence of these contaminants raised questions about any observed effects rendering the clinical investigations useless. (Walsh 2005)
After the introduction of a renewed PC-Spes2, produced using improved quality control, only one preliminary study has been reported. Eighteen patients with advanced hormone refractory prostate cancer were included in a 3-month, prospective, open pilot study. The product used was analyzed and found to be free from diethylstilbestrol and warfarin. However, ten out of 18 patients withdrew due to severe diarrhoea and only five patients remained in the study at the end of the 3-month duration, which does not allow any conclusions to be drawn. (Shabbir 2008).
Adverse events
Several adverse events were observed. It is, however, possible that some toxic effects were caused by the synthetic drugs, such as warfarin and diethylstilbestrol that were found in PC-SPES samples. (Weinrobe 2001)
In studies and trials the following adverse effects were observed: gynecomastia was near universal; leg cramps, nipple tenderness, loss of libido and impotency were common; less common were nausea and vomiting; and uncommon adverse effect was thromboembolism. (Kosty 2004; Marks 2002; Cordell 2002; Das 2002)
Several case reports of toxic effects of PC-SPES were published. The more serious complications include pulmonary embolism and disseminated intravascular coagulation. (Olaku 2011; Lock 2001; Schiff 2002).
Contraindications / interactions
Because of the estrogenic effects of PC-SPES, it might interfere with conventional hormone therapies for prostate cancer if used concurrently. (Lee 2005) Nevertheless, there are no reports on contraindications or important drug-herb interactions so far. (Cordell 2002) As long as not every ingredient is identified, it is, however, difficult to assess reliably any contraindication or risk of herb-drug interactions.
Warnings
Withdrawal response to PC-SPES was noted, in spite of previous experience suggesting a rapid rise in PSA after discontinuation of the PC-SPES therapy. (Oh 2002; Chaudhary 2004)
Quality issues
The manufacturers have failed to control the quality of PC-SPES and to apply good manufacturing practices (GMP) during its production leading to its contamination with diethylstilbestrol and ethinyl estradiol16,17 as well as warfarin and indomethacin18.
Blumenthal M. The rise and fall of PC-SPES: New generation of herbal supplement, adulterated product, or new drug? Integrative Cancer Therapies 2002;1(3):266-270.
Chaudhary UB, Rashid M, Keane TE. PC-SPES withdrawal response. Acta Oncologica 2004;43:772-773.
Cordell GA. PC-SPES: A brief overview. Integrative Cancer Therapies 2002;1(3):271-286.
Das P, Kaplan I. The role of PC-SPES, selenium, and vitamin E in prostate cancer. Oncology 2002;16(3):285-291.
de la Taille A, Buttyan R, Hayek O, Bagiella E, Shabsigh A, Burchardt M, Burchardt T, Chopin DK, Katz AE. Herbal therapy PC-SPES: In vitro effects and evaluation of its efficacy in 69 patients with prostate cancer. The Journal of Urology 2000;164:1229-1234.
de la Taille A, Hayek OR, Burchardt M, Burchardt T, Katz AE. Role of herbal compounds (PC-SPES) in hormone-refractory prostate cancer: Two case reports. The Journal of Alternative and Complementary Medicine 2000;6(5):449-451.
de la Taille A, Hayek OR, Buttyan R, Bagiella E, Burchardt M, Katz AE. Effects of a phytotherapeutic agent, PC-SPES, on prostate cancer: A preliminary investigation on human cell lines and patients. BJU International 1999;84:845-850.
DiPaola RS, Zhang H, Lambert GH, Meeker R, Licitra E, Rafi MM, Zhu BT, Spaulding H, Goodin S, Toledano MB, Hait WN, Gallo MA. Clinical and biological activity of an estrogenic herbal combination (PC-SPES) in prostate cancer. The New England Journal of Medicine 1998;339(12):785-791.
Guns ES, Goldenberg SL, Brown PN. Mass spectral analysis of PC-SPES confirms the presence of diethylstilbestrol. The Canadian Journal of Urology 2002;9(6):1684-1688.
Ko R, Wilson RD, Loscutoff S. PC-SPES. Urology 2003;61:1292-1292. Kosty MP. PC-SPES: Hope or hype? Journal of Clinical Oncology 2004;22(18):3657-3659. Lee CO. Complementary and alternative medicine patients are talking about: PC-SPES. Clinical Journal of Oncology Nursing 2005;9(1):113-114.
Lock M, Loblaw DA, Choo R, Imrie K. Disseminated intravascular coagulation and PC-SPES: A case report and literature review. The Canadian Journal of Urology 2001;8(4):1326-1329.
Marks LS, DiPaola RS, Nelson P, Chen S, Heber D, Belldegrun AS, Lowe FC, Fan J, Leaders FE, Pantuck AJ, Tyler VE. PC-SPES: Herbal formulation for prostate cancer. Urology 2002;60(3):369-375.
Meyer JP, Gillat DA. PC-SPES: A herbal therapy for the treatment of hormone refractory prostate cancer. Prostate Cancer and Prostatic Diseases 2002;5:13-15.
Moyad MA, Pienta KJ, Montie JE. Use of PC-SPES, a commercially available supplement for prostate cancer, in a patient with hormone-naive disease. Urology 1999;54(2):319-323.
Oh WK, George DJ, Hackmann K, Manola J, Kantoff PW. 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, George DJ, Kantoff PW. Rapid rise of serum prostate specific antigen levels after discontinuation of the herbal therapy PC-SPES in patients with advanced prostate carcinoma: report of four cases. Cancer 2002;94(3):686-689.
Oh WK, Kantoff PW, Weinberg V, Jones G, Rini BI, Derynck MK, Bok R, Smith MR, Bulbey GJ, Rosen RT, DiPaola RS, Small EJ. Prospective, multicenter, randomized phase II trial of the herbal supplement, PC-SPES, and diethylstilbestrol in patients with androgen-independent prostate cancer. Journal of Clinical Oncology 2004;22(18):3705-3712.
Olaku O, White JD. Herbal therapy use by cancer patients: A literature review on case reports. European Journal of Cancer 2011;47:508-514.
Pfeifer BL, Pirani JF, Hamann SR, Klippel KF. PC-SPES, a dietary supplement for the treatment of hormone-refractory prostate cancer. BJU International 2000;85:481-485.
Schiff JD, Ziecheck WS, Choi B. Pulmonary embolus related to PC-SPES use in a patient with PSA recurrence after radical prostatectomy. Urology 2002;59(3):444vii-444viii.
Shabbir M, Love J, Montgomery B. Phase I trial of PC-spes2 in advanced hormone refractory prostate cancer. Oncology Reports 2008;19:831-835.
Small EJ, Frohlich MW, Bok R, Shinohara K, Grossfeld G, Rozenblat Z, Kelly WK, Corry M, Reese DM. Prospective trial of the herbal supplement PC-SPES in patients with progressive prostate cancer. Journal of Clinical Oncology 2000;18(21):3595-3603.
Sovak M, Seligson AL, Konas M, Hajduch M, Dolezal M, Machala M, Nagourney R. Herbal composition PC-SPES for management of prostate cancer: Identification of active principles. Journal of the National Cancer Institute 2002;94(17):1275-1281.
Walsh PC. Editorial comment on “Prospective, multicenter, randomized phase II trial of the herbal supplement, PC-SPES, and diethylstilbestrol in patients with androgen-independent prostate cancer”. The Journal of Urology 2005;173:1966-1967.
Weinrobe MC, Montgomery B. Acquired bleeding diathesis in a patient taking PC-SPES. The New England Journal of Medicine 2001;345(16):1213-1214. Yip I, Cudiamat M, Chim D. PC-SPES for treatment of prostate cancer: Herbal medicine. Current Urology Reports 2003;4:253-257.
