PC-SPES

Liene Dhooghe and the CAM Cancer Consortium | Published 14/09/2020

Abstract and key points
What is it?
Does it work?
Is it safe?
References

PC-SPES is a combination of eight herbs: Dendranthema morifolium; Isatis indigotica; Glycyrrhiza uralensis; Ganoderma lucidum; Panax pseudoginseng; Rabdosia rubescens; Serenoa repens; and Scutellaria baicalensis. The product was promoted for prostate health and was popular with prostate cancer patients. The original PC-SPES product was recalled by the FDA due to contamination with prescription drugs and withdrawn from the market by the producer. Numerous products claiming to be substitutes of PC-SPES are, however, still available.

There is a lack of double-blind clinical trials and only limited data from case reports and observational or preliminary studies are available. Although overall a significant decrease in prostate-specific antigen levels was observed, 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. Other similar products have not been clinically investigated.

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

Liene Dhooghe, CAM Cancer Consortium. PC-SPES [online document], August 25, 2020.

Document history

Assessed as up to date in August 2020 by Barbara Wider.

Assessed as up to date in January 2019 by Barbara Wider.
Assessed as up to date in February 2017 by Barbara Wider.
Assessed as up to date in January 2015 by Barbara Wider.
Assessed as up to date in August 2013 by Barbara Wider.
Summary first published in January 2012, authored by Liene Dhooghe.

Scientific name(s)/brand name(s)/common name(s)

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, but was recalled by the FDA due to contamination with prescription drugs in 2002 and is no longer officially available1,2. Active Botanicals Ltd (UK) has redeveloped PC-spes2, which is not yet commercially available. Other similar products claim to be the replacement supplement for PC-SPES, however, often different combinations of plants are used (for example Prostectan, Prostasol, PC-Care, PC-Hope)3.

Ingredient(s)

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)4.

Application and dosage

The recommended dose for “prostate health” was three to six capsules of PC-SPES per day on an empty stomach.

History/provider(s) / Legal issues

PC-SPES was commercially available from 1996 to 2002, until the California Department of Health Services Food and Drug Branch discovered warfarin and indomethacin in PC-SPES capsules. Independent laboratories also found diethylstilbesterol in some samples2. It was recalled by the FDA and voluntarily withdrawn from the market by BotanicLab. However, it remains accessible through internet and telephone order4. Recently Active Botanicals Ltd (UK) has redeveloped PC-spes2, which is standardized against five active ingredients (baicalin, oridonin, wogonin, isoliquiritigenin, and licochacone A), compared to only two in the old PC-SPES (baicalin and oridonin). Independent quality control demonstrated no contaminants5. This product is, however, not yet commercially available. Other similar products claiming to be substitutes of PC-SPES, can be purchased online (for example Prostectan, Prostasol, PC-Care).

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 lines6. There are components that show estrogenic activity or inhibit 5-alpha reductase6. The extracts can induce apoptosis and can suppress cell growth by restricting cell cycle progression at G(1)/S phase7,8.

Claims of efficacy / Alleged indication(s)

PC-SPES is commercialized for prostate health and strengthening of the immune system. Scientific research is investigating its efficacy in androgen-independent and androgen-dependent prostate cancer.

Prevalence of use

In 2002, approximately 10,000 patients with prostate cancer were using PC-SPES in addition to standard therapy or as a sole treatment6.

Cost(s) and expenditures

In 2002, a bottle of 60 capsules of PC-SPES cost US$ 108.

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 have been conducted9. A crossover study was interrupted because of observed contamination of PC-SPES with several prescription drugs.

Clinical trials

Following first observational and preliminary studies with PC-SPES, reporting a remarkable reduction in PSA levels10 and a significant improvement in quality of life and reduction in pain ratings11, several phase II studies were conducted in patients with androgen-insensitive prostate cancer. Overall a decline in PSA of at least 50% was observed12-15. In a randomized phase II clinical trial with crossover design, comparing PC-SPES to diethylstilbestrol, the analysis of the used PC-SPES showed, however, quantities of diethylstilbestrol and ethinyl estradiol16,17. Warfarin and indomethacin were also detected and the study therefore terminated18. The presence of these contaminants questions any observed effects rendering the clinical investigations useless19.

After the introduction of the renewed PC-Spes2, produced using improved quality control, only one study has been reported. It is a single-centre, prospective, open pilot study in 18 patients with advanced hormone refractory prostate cancer. The product used was analyzed and found to be free from diethylstilbestrol and warfarin. The results were not as positive compared to the described response of the original PC-SPES5.

Case reports

Several case reports were published, reporting a substantial decrease in serum prostate-specific antigen (PSA) levels following a regular use of PC-SPES20-24.

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 samples25.

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 thromboembolism6,8,26,27.

Several case reports of toxic effects of PC-SPES were published. The more serious complications include pulmonary embolism and disseminated intravascular coagulation21,22,28.

Contraindications / interactions

Because of the estrogenic effects of PC-SPES, it might interfere with conventional hormone therapies for prostate cancer if used concurrently4. Nevertheless, there are no reports on contraindications or important drug-herb interactions so far26. 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 therapy23,29.

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.

  1. 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. Accessed 14th of September 2020.
  2. 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. Accessed 14th of September 2020.
  3. Natural Treatments for Prostate Cancer (available on the internet). Example: Accessed 14th of September 2020.
  4. Lee CO. Complementary and alternative medicine patients are talking about: PC-SPES. Clinical Journal of Oncology Nursing 2005;9(1):113-114. Accessed 14th of September 2020.
  5. Shabbir M, Love J, Montgomery B. Phase I trial of PC-spes2 in advanced hormone refractory prostate cancer. Oncology Reports 2008;19:831-835. Accessed 14th of September 2020.
  6. Kosty MP. PC-SPES: Hope or hype? Journal of Clinical Oncology 2004;22(18):3657-3659. Accessed 14th of September 2020.
  7. Yip I, Cudiamat M, Chim D. PC-SPES for treatment of prostate cancer: Herbal medicine. Current Urology Reports 2003;4:253-257. Accessed 14th of September 2020.
  8. 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. Accessed 14th of September 2020.
  9. 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. Accessed 14th of September 2020.
  10. 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. Accessed 14th of September 2020.
  11. 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. Accessed 14th of September 2020.
  12. 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. Accessed 15th of September 2020.
  13. 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. Accessed 15th of September 2020.
  14. 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. Accessed 15th of September 2020.
  15. 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. Accessed 15th of September 2020.
  16. 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.  Accessed 15th of September 2020.
  17. 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.  Accessed 15th of September 2020.
  18. Ko R, Wilson RD, Loscutoff S. PC-SPES. Urology 2003;61:1292-1292.
  19. 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.
  20. 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.  Accessed 15th of September 2020.
  21. Olaku O, White JD. Herbal therapy use by cancer patients: A literature review on case reports. European Journal of Cancer 2011;47:508-514.' Accessed 15th of September 2020.
  22. 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. Accessed 15th of September 2020.
  23. 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. Accessed 15th of September 2020.
  24. 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. Accessed 15th of September 2020.
  25. Weinrobe MC, Montgomery B. Acquired bleeding diathesis in a patient taking PC-SPES. The New England Journal of Medicine 2001;345(16):1213-1214. Accessed 15th of September 2020.
  26. Cordell GA. PC-SPES: A brief overview. Integrative Cancer Therapies 2002;1(3):271-286. Accessed 15th of September 2020.
  27. Das P, Kaplan I. The role of PC-SPES, selenium, and vitamin E in prostate cancer. Oncology 2002;16(3):285-291. Accessed 15th of September 2020.
  28. 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. Accessed 15th of September 2020.
  29. Chaudhary UB, Rashid M, Keane TE. PC-SPES withdrawal response. Acta Oncologica 2004;43:772-773. Accessed 15th of September 2020.

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