Purpose of This PDQ Summary
Overview
General Information
Laboratory/Preclinical Studies
Animal Studies
Clinical Trials
Adverse Effects
Substitutes for PC-SPES
Overall Level of Evidence for PC-SPES
Changes to This Summary (09/04/2008)
More Information

Purpose of This PDQ Summary

This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the use of PC-SPES as a treatment for prostate cancer. This summary is reviewed regularly and updated as necessary by the PDQ Cancer Complementary and Alternative Medicine Editorial Board ¹.

Information about the following is included in this summary:

• A brief history of PC-SPES research.
• The results of clinical studies of PC-SPES.
• Possible side effects of PC-SPES use.
• Discussion regarding the contamination of PC-SPES and its withdrawal from avenues of distribution.

This summary is intended as a resource to inform and assist clinicians and other health professionals who care for cancer patients. It does not provide formal guidelines or recommendations for making health care decisions.

Some of the reference citations in the summary are accompanied by a level of evidence designation. These designations are intended to help the readers assess the strength of the evidence supporting the use of specific interventions or treatment strategies. The PDQ Cancer Complementary and Alternative Medicine Editorial Board uses a formal evidence ranking system ² in developing its level of evidence designations. These designations should not be used as a basis for reimbursement determinations.

This summary is also available in a patient version ³, which is written in less technical language.

Overview

This complementary and alternative medicine (CAM) information summary provides an overview of the use of PC-SPES as a treatment for cancer. The summary includes a brief history of PC-SPES research, the results of clinical trials, and possible adverse effects of PC-SPES. Included in this summary is a discussion of the contamination of PC-SPES and its withdrawal from avenues of distribution.

This summary contains the following key information:

• PC-SPES is a patented mixture of eight herbs.
• PC-SPES was sold as a dietary supplement to support and promote healthy prostate function.
• Each herb used in PC-SPES has been reported to have anti-inflammatory, antioxidant, or anticarcinogenic properties.
• PC-SPES was recalled and withdrawn from the market because certain batches were contaminated with Food and Drug Administration–controlled prescription drugs.
• The manufacturer is no longer in operation, and PC-SPES is no longer being made.
• There is evidence from both laboratory and animal studies to suggest that PC-SPES had some effect in inhibiting prostate cancer cell growth and prostate-specific antigen (PSA) expression, but it is not known whether these results were caused by contaminants such as diethylstilbestrol (DES), which is an estrogenic compound, the herbs in PC-SPES, or their combination.
• Evidence from clinical trials has shown that PC-SPES lowers PSA and testosterone levels in humans, but it is not known whether these results were caused by contaminants, the herbs in PC-SPES, or their combination.
• There is some evidence to suggest that PC-SPES has some anticancer effects that are not related to estrogen-like activity.
• Although there are products that claim to be substitutes for PC-SPES, they are not the patented original formulation. Few of these products have been the subject of laboratory or clinical trials reported in the peer-reviewed medical literature.

General Information

Note: A separate PDQ summary on Prostate Cancer Treatment ⁴ is also available.

PC-SPES is a patented herbal mixture that was sold as a dietary supplement and used as a complementary and alternative medicine (CAM) treatment for prostate cancer. It is a combination of eight herbs: baikal skullcap (Scutellaria baicalensis Georgi), chrysanthemum (Dendranthema morifolium [Ramat.] Tzvelev [synonym Chrysanthemum morifolium]), ganoderma (Ganoderma lucidum [Curtis:fr] Karst.), isatis (Isatis indigotica Fort.), licorice (Glycyrrhiza glabra L. or Glycyrrhiza uralensis Fisch. ex DC.), Panax ginseng C.A. Meyer or pseudo ginseng (Panax pseudoginseng var. notoginseng Hoo & tseng [synonym Panax notoginseng (Burkill)] F.H.Chen), Isodon rubescens (Hemsl.) Hara (synonym Rabdosia rubescens [Hemsl.] Hara), and saw palmetto (Serenoa repens [Bartr.] Small). With the exception of saw palmetto, the herbs in PC-SPES have been used individually or in combination in Traditional Chinese Medicine (TCM) for a variety of health problems, including those of the prostate, for hundreds of years.[1,2]

PC-SPES is an herbal product that resulted from a collaboration between a chemist at the New York Medical College in Valhalla, New York, and a Chinese herbalist and doctor of TCM in China. Their idea was to combine TCM with the scientific techniques of Western laboratory research. In the United States, a series of in vitro and in vivo laboratory studies was started on the mixture of herbs used in TCM specially formulated to treat prostate problems. Researchers published the results of these studies, which showed promising anticancer activity from PC-SPES.[3-11]

In 1997, the herbal formula for PC-SPES was patented in the United States.[12] A company, BotanicLab (Brea, California), was formed to produce, distribute, and sell the product. PC-SPES was sold through the BotanicLab Web site (the Web site was taken down after PC-SPES was recalled) and through selected distributors. Anecdotal information about the product and its positive effects was widely circulated on the Internet through Web sites that informed prostate cancer patients about new developments in treatment. At the same time, the published papers were being read by the scientific community, and the findings were presented at various conferences. As a result, clinicians and researchers began looking at PC-SPES as one of the first viable treatments to come out of the alternative medicine community.

The manufacturing process for PC-SPES has been described by the manufacturer as follows: extracts of raw plant material were obtained from the specified plants, which were grown in particular geographic regions in China and harvested at certain times of the year to reduce the natural variation inherent in any biological product. The extracts were shipped to the United States, where high-performance liquid chromatography (HPLC) was used to monitor the key active compounds—which are believed to be directly related to the clinical effects—for batch-to-batch reproducibility. Activity-related biomarkers were kept in a constant concentration from lot to lot. A commercial testing laboratory (Truesdail Laboratory, Tustin, California) was used to guarantee that each batch was free from contamination with heavy metals, pesticides, microorganisms and products, and prescription drugs. Each lot was standardized by an anticancer bioassay for an effective dose of 50% in vitro inhibition of cell growth using human LNCaP cells for androgen-dependent (AD) prostate cancer and DU-145 cells for androgen-independent (AI) prostate cancer. The powder was then encapsulated, bottled, labeled, and sterilized at the BotanicLab facility.[10]

In 2001, allegations that PC-SPES contained the synthetic estrogen diethylstilbestrol (DES) started to appear on e-mail listservs used by prostate cancer patients and in online newsletters. Prostate cancer patients who were taking PC-SPES noticed that their recent medication was not as effective as the previous batches.[13] A sample of PC-SPES submitted to a testing laboratory by BotanicLab in August 2001 found no DES. BotanicLab posted the letter from the laboratory on their Web site, claiming that PC-SPES contained no DES. However, in other tests of six different lots of PC-SPES received from two different sources in August 2001, Rocky Mountain Instrumental Laboratory found varying amounts of DES in three lots. More tests done for the California Department of Health Services in February 2002 did not find DES but did find warfarin, a prescription drug used as a blood thinner.[14]

The presence of a synthetic estrogen such as DES was suspected early in the clinical use of PC-SPES after reports in the literature discussed the mixture’s estrogen-like ability to lower prostate-specific antigen (PSA) levels in AD prostate cancer patients. In addition, the side effects of treatment were similar to those of estrogen therapy. [15-17] In one study, patients who showed the most response to PC-SPES were also those who were the most responsive to DES. Reviewed in [11,18] The same study also attempted to find out whether DES or similar compounds were present in PC-SPES. Transcriptional activation assays in yeast strain PL3 Saccharomyces cerevisiae using an ethanolic extract of PC-SPES showed estrogenic activity similar to 1nM estradiol. In addition, ovariectomized CD-1 mice showed substantially increased uterine weights. HPLC, gas chromatography, and mass spectrometry did not reveal the presence of DES but rather that of a compound with similar chemical characteristics. The authors of the report concluded that PC-SPES contains estrogenic compounds that are distinct from DES or other synthetic estrogens.[18]

A definitive evaluation of PC-SPES analyzed specific lots of PC-SPES capsules manufactured from 1996 to 2001.[19] In addition to using HPLC to isolate, identify, and quantify the synthetic drugs and active phytoestrogens, this study also identified components using proton nuclear magnetic resonance, gas chromatography/mass spectrometry, and mass spectra analysis. Tests showed the presence of the synthetic drugs indomethacin (a nonsteroidal anti-inflammatory drug not previously reported in the literature or found in other testing), DES, and warfarin. Testing was also done for concentrations of the two naturally occurring phytosterols, licochalcone A and baicalin. Test results indicated a history of rising and falling levels of contamination by the three synthetic drugs and a recent rise in the naturally occurring phytochemicals in PC-SPES. Lots of PC-SPES manufactured in 1996 through mid-1999 contained indomethacin ranging from 1.07 to 13.19 mg/g and DES ranging from 107.28 to 159.27 µg/g and were 2 to 6 times more antineoplastic and up to 50 times more estrogenic than lots manufactured after the spring of 1999. In vitro testing of ethanolic extracts of PC-SPES against LNCaP, PC-3, and DU-145 prostate cancer cell lines showed a decrease in both antineoplasticity and estrogenicity in lots of PC-SPES manufactured in June 1998 through August 2001, which correlated with the amount of DES and indomethacin contamination.[19] Another in vitro test of suspected lots of PC-SPES manufactured from 2000 to 2001 also showed the presence of DES.[20] The table below shows the lot numbers, date of manufacture, and amount of DES contamination.

Refer to chart 1 ⁶ below showing the lot numbers, date of manufacture, and amount of DES contamination.

Although the laboratory testing showed that certain lots of the mixture contained indomethacin, warfarin, and DES, the amount of DES present may not have accounted for all of the estrogenic effect of PC-SPES. There is some evidence that the mixture acts differently from DES at the molecular level.[7,21] In addition, its anticancer effects on both AI prostate cancer and AD prostate cancer may point to a mechanism other than estrogen-like activity.[19,22,23] The in vitro activity of PC-SPES against cancer cells other than prostate also gives rise to the speculation that its estrogen-like qualities might not account for all of the mixture’s anticancer activity.[24,25]

Considerable research has been conducted on the anticancer properties of the eight individual botanicals in PC-SPES.

Baikal skullcap (Scutellaria baicalensis)—Chinese name huang qin—contains baicalin and wogonin, two active flavones. Baicalin converts to baicalein, which is another active flavone. In vitro, baicalin and baicalein inhibit cell growth of AD LNCaP and JCA-1 AI human prostate cancer cell lines [24,25], as well as inducing apoptosis in human LNCaP cells.[26] Baicalin also shows antimutagenic and antioxidant activity in vitro as well as free radical scavenging ability.[27-32]

Licorice (Glycyrrhiza glabra or Glycyrrhiza uralensis)—Chinese name gan cao—contains the very active flavonoid licochalcone A, which has demonstrated in vitro estrogenic activity.[33] This botanical shows a broad range of anticancer activity in vitro. It enhances the cytotoxicity of commonly used anticancer drugs and induces apoptosis in MCF-7 human breast cancer and HL-60 promyelocytic leukemia cell lines.[33-36]

Reishi mushroom (Ganoderma lucidum [Curtis: fr.] Karst.)—Chinese name ling zhi— has been shown to aid in the recovery of leukocyte counts in irradiated mice in a dose-dependent manner. It contains the polysaccharide G009, which has demonstrated antioxidant behavior against HL-60 cells in vitro and dose-dependent inhibition of lipid peroxidation in rat brain cells in vitro.[37-41]

Isatis (Isatis indigotica)—Chinese name da qing ve—contains active agents in each part of the plant.[2] TCM has different names for the medicinals coming from the leaf, stem, and root and uses these plant products for different purposes. Indirubin, an active ingredient, and its analogs have demonstrated inhibition of cyclin-dependent kinases in human mammary carcinoma cell line MCF-7 in vitro.[42]

Ginseng (Panax ginseng or Panax pseudoginseng var. notoginseng)— Chinese name tianqi—contains ginsenosides and saponins. Of the 30 ginsenosides that have been isolated from Panax ginseng, only the 20(S)-protopanaxadiol type R3 has inhibited cell growth and suppressed PSA expression, androgen receptor and 5-alpha-reductase activity, and PCNA production in vitro.[43-45]

Chrysanthemum flowers (Dendranthema morifolium)—Chinese name ju hua—contain triterpene diols and triols. Arnidiol exhibited cytotoxicity in vitro against 58 of the 60 human cancer cell lines developed by the National Cancer Institute (NCI) Developmental Therapeutics Program.[46]

The botanical rabdosia rubescens (Isodon rubescens)—Chinese name dong ling cao—has two very active agents, oridonin and rubesencin b. Oridonin inhibits DNA synthesis in vitro Reviewed in [1], and rubesencin b inhibited cell growth in cancer cell lines in vitro and in a mouse model.[47]

Saw palmetto (Serenoa repens) is the only botanical in PC-SPES that is not used in TCM. There is strong evidence from human trials that saw palmetto has some activity against benign prostatic hypertrophy (BPH), including improved urine flow and less erectile dysfunction when compared with placebo or finasteride. S repens also exhibits antiestrogenic activity in placebo-controlled BPH trials. In LNCaP cells, S repens produced apoptosis in vitro.[48-52]

Exactly how PC-SPES works in the body is still unknown. The presence of contaminants and varying amounts of the active agents in each lot of PC-SPES complicate the interpretation of any results from studies that might lead to an explanation of its mechanisms of action. More studies of the individual components of the mixture and testing of a standard formulation that is free of contaminants are needed before any conclusions can be reached about the level of cytotoxicity, antineoplasticity, or estrogenicity of PC-SPES.

The National Center for Complementary and Alternative Medicine (NCCAM) stopped funding to studies of PC-SPES after the drug contamination was detected and made public, although the laboratory studies were later resumed. Refer to The Future of PC SPES Research Funding by NCCAM ⁷.

References

1. Huang KC, Williams WM: The Pharmacology of Chinese Herbs. 2nd ed. Boca Raton, Fl: CRC Press, 1998. 
   
   
2. Zhu YP: Chinese Materia Medica: Chemistry, Pharmacology, and Applications. Amsterdam, The Netherlands: Harwood Academic, 1998. 
   
   
3. Halicka HD, Ardelt B, Juan G, et al.: Apoptosis and cell cycle effects induced by extracts of the Chinese herbal preparation PC SPES. Int J Oncol 11: 437-48, 1997. 
   
   
4. Hsieh T, Chen SS, Wang X, et al.: Regulation of androgen receptor (AR) and prostate specific antigen (PSA) expression in the androgen-responsive human prostate LNCaP cells by ethanolic extracts of the Chinese herbal preparation, PC-SPES. Biochem Mol Biol Int 42 (3): 535-44, 1997.  [PUBMED Abstract]
   
   
5. Chenn S: In vitro mechanism of PC SPES. Urology 58 (2 Suppl 1): 28-35; discussion 38, 2001.  [PUBMED Abstract]
   
   
6. Hsieh TC, Wu JM: Mechanism of action of herbal supplement PC-SPES: elucidation of effects of individual herbs of PC-SPES on proliferation and prostate specific gene expression in androgen-dependent LNCaP cells. Int J Oncol 20 (3): 583-8, 2002.  [PUBMED Abstract]
   
   
7. Chen S, Ruan Q, Bedner E, et al.: Effects of the flavonoid baicalin and its metabolite baicalein on androgen receptor expression, cell cycle progression and apoptosis of prostate cancer cell lines. Cell Prolif 34 (5): 293-304, 2001.  [PUBMED Abstract]
   
   
8. Kubota T, Hisatake J, Hisatake Y, et al.: PC-SPES: a unique inhibitor of proliferation of prostate cancer cells in vitro and in vivo . Prostate 42 (3): 163-71, 2000.  [PUBMED Abstract]
   
   
9. Darzynkiewicz Z, Traganos F, Wu JM, et al.: Chinese herbal mixture PC SPES in treatment of prostate cancer (review). Int J Oncol 17 (4): 729-36, 2000.  [PUBMED Abstract]
   
   
10. Marks LS, DiPaola RS, Nelson P, et al.: PC-SPES: herbal formulation for prostate cancer. Urology 60 (3): 369-75; discussion 376-7, 2002.  [PUBMED Abstract]
    
    
11. Pirani JF: The effects of phytotherapeutic agents on prostate cancer: an overview of recent clinical trials of PC SPES. Urology 58 (2 Suppl 1): 36-8, 2001.  [PUBMED Abstract]
    
    
12. Chen S, Wang X: Herbal Composition for Treating Prostate Carcinoma. US Patent 5665393. September 9, 1997. Washington, DC: US Patent and Trademark Office, 1997. Available online ⁸. Last accessed March 28, 2007. 
    
    
13. PSA Rising: Prostate Cancer Survivor News, Info and Support. New York, NY: PSA Rising, 2005. Available online ⁹. Last accessed November 26, 2007. 
    
    
14. Ko R, Wilson RD, Loscutoff S: PC-SPES. Urology 61 (6): 1292, 2003.  [PUBMED Abstract]
    
    
15. 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 57 (1): 122-6, 2001.  [PUBMED Abstract]
    
    
16. 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 94 (3): 686-9, 2002.  [PUBMED Abstract]
    
    
17. de la Taille A, Hayek OR, Burchardt M, et al.: Role of herbal compounds (PC-SPES) in hormone-refractory prostate cancer: two case reports. J Altern Complement Med 6 (5): 449-51, 2000.  [PUBMED Abstract]
    
    
18. 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 339 (12): 785-91, 1998.  [PUBMED Abstract]
    
    
19. 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 94 (17): 1275-81, 2002.  [PUBMED Abstract]
    
    
20. Guns ES, Goldenberg SL, Brown PN: Mass spectral analysis of PC-SPES confirms the presence of diethylstilbestrol. Can J Urol 9 (6): 1684-8; discussion 1689, 2002.  [PUBMED Abstract]
    
    
21. Bonham M, Arnold H, Montgomery B, et al.: Molecular effects of the herbal compound PC-SPES: identification of activity pathways in prostate carcinoma. Cancer Res 62 (14): 3920-4, 2002.  [PUBMED Abstract]
    
    
22. Reynolds T: Contamination of PC-SPES remains a mystery. J Natl Cancer Inst 94 (17): 1266-8, 2002.  [PUBMED Abstract]
    
    
23. Malkowicz SB: The role of diethylstilbestrol in the treatment of prostate cancer. Urology 58 (2 Suppl 1): 108-13, 2001.  [PUBMED Abstract]
    
    
24. Huerta S, Arteaga JR, Irwin RW, et al.: PC-SPES inhibits colon cancer growth in vitro and in vivo. Cancer Res 62 (18): 5204-9, 2002.  [PUBMED Abstract]
    
    
25. Schwarz RE, Donohue CA, Sadava D, et al.: Pancreatic cancer in vitro toxicity mediated by Chinese herbs SPES and PC-SPES: implications for monotherapy and combination treatment. Cancer Lett 189 (1): 59-68, 2003.  [PUBMED Abstract]
    
    
26. Chan FL, Choi HL, Chen ZY, et al.: Induction of apoptosis in prostate cancer cell lines by a flavonoid, baicalin. Cancer Lett 160 (2): 219-28, 2000.  [PUBMED Abstract]
    
    
27. Okita K, Li Q, Murakamio T, et al.: Anti-growth effects with components of Sho-saiko-to (TJ-9) on cultured human hepatoma cells. Eur J Cancer Prev 2 (2): 169-75, 1993.  [PUBMED Abstract]
    
    
28. Matsuzaki Y, Kurokawa N, Terai S, et al.: Cell death induced by baicalein in human hepatocellular carcinoma cell lines. Jpn J Cancer Res 87 (2): 170-7, 1996.  [PUBMED Abstract]
    
    
29. Kimura Y, Matsushita N, Okuda H: Effects of baicalein isolated from Scutellaria baicalensis on interleukin 1 beta- and tumor necrosis factor alpha-induced adhesion molecule expression in cultured human umbilical vein endothelial cells. J Ethnopharmacol 57 (1): 63-7, 1997.  [PUBMED Abstract]
    
    
30. Hsieh TC, Lu X, Chea J, et al.: Prevention and management of prostate cancer using PC-SPES: a scientific perspective. J Nutr 132 (11 Suppl): 3513S-3517S, 2002.  [PUBMED Abstract]
    
    
31. Ikezoe T, Chen SS, Heber D, et al.: Baicalin is a major component of PC-SPES which inhibits the proliferation of human cancer cells via apoptosis and cell cycle arrest. Prostate 49 (4): 285-92, 2001.  [PUBMED Abstract]
    
    
32. Hsu SL, Hsieh YC, Hsieh WC, et al.: Baicalein induces a dual growth arrest by modulating multiple cell cycle regulatory molecules. Eur J Pharmacol 425 (3): 165-71, 2001.  [PUBMED Abstract]
    
    
33. Gao Z, Huang K, Yang X, et al.: Free radical scavenging and antioxidant activities of flavonoids extracted from the radix of Scutellaria baicalensis Georgi. Biochim Biophys Acta 1472 (3): 643-50, 1999.  [PUBMED Abstract]
    
    
34. Armanini D, Bonanni G, Palermo M: Reduction of serum testosterone in men by licorice. N Engl J Med 341 (15): 1158, 1999.  [PUBMED Abstract]
    
    
35. Rafi MM, Vastano BC, Zhu N, et al.: Novel polyphenol molecule isolated from licorice root (Glycrrhiza glabra) induces apoptosis, G2/M cell cycle arrest, and Bcl-2 phosphorylation in tumor cell lines. J Agric Food Chem 50 (4): 677-84, 2002.  [PUBMED Abstract]
    
    
36. Rafi MM, Rosen RT, Vassil A, et al.: Modulation of bcl-2 and cytotoxicity by licochalcone-A, a novel estrogenic flavonoid. Anticancer Res 20 (4): 2653-8, 2000 Jul-Aug.  [PUBMED Abstract]
    
    
37. Wang ZY, Nixon DW: Licorice and cancer. Nutr Cancer 39 (1): 1-11, 2001.  [PUBMED Abstract]
    
    
38. Bao XF, Wang XS, Dong Q, et al.: Structural features of immunologically active polysaccharides from Ganoderma lucidum. Phytochemistry 59 (2): 175-81, 2002.  [PUBMED Abstract]
    
    
39. Chen WC, Hau DM, Lee SS: Effects of Ganoderma lucidum and krestin on cellular immunocompetence in gamma-ray-irradiated mice. Am J Chin Med 23 (1): 71-80, 1995.  [PUBMED Abstract]
    
    
40. Hsu HY, Lian SL, Lin CC: Radioprotective effect of Ganoderma lucidum (Leyss. ex. Fr.) Karst after X-ray irradiation in mice. Am J Chin Med 18 (1-2): 61-9, 1990.  [PUBMED Abstract]
    
    
41. Lee JM, Kwon H, Jeong H, et al.: Inhibition of lipid peroxidation and oxidative DNA damage by Ganoderma lucidum. Phytother Res 15 (3): 245-9, 2001.  [PUBMED Abstract]
    
    
42. Marko D, Schätzle S, Friedel A, et al.: Inhibition of cyclin-dependent kinase 1 (CDK1) by indirubin derivatives in human tumour cells. Br J Cancer 84 (2): 283-9, 2001.  [PUBMED Abstract]
    
    
43. Liu WK, Xu SX, Che CT: Anti-proliferative effect of ginseng saponins on human prostate cancer cell line. Life Sci 67 (11): 1297-306, 2000.  [PUBMED Abstract]
    
    
44. Yun TK, Lee YS, Lee YH, et al.: Anticarcinogenic effect of Panax ginseng C.A. Meyer and identification of active compounds. J Korean Med Sci 16 (Suppl): S6-18, 2001.  [PUBMED Abstract]
    
    
45. Surh YJ, Na HK, Lee JY, et al.: Molecular mechanisms underlying anti-tumor promoting activities of heat-processed Panax ginseng C.A. Meyer. J Korean Med Sci 16 (Suppl): S38-41, 2001.  [PUBMED Abstract]
    
    
46. Ukiya M, Akihisa T, Tokuda H, et al.: Constituents of Compositae plants III. Anti-tumor promoting effects and cytotoxic activity against human cancer cell lines of triterpene diols and triols from edible chrysanthemum flowers. Cancer Lett 177 (1): 7-12, 2002.  [PUBMED Abstract]
    
    
47. Jing JY, Reed E: Preliminary study of the effect of selected Chinese natural drugs on human ovarian cancer cells. Oncol Rep 2: 571-5, 1995. 
    
    
48. Marks LS, Hess DL, Dorey FJ, et al.: Tissue effects of saw palmetto and finasteride: use of biopsy cores for in situ quantification of prostatic androgens. Urology 57 (5): 999-1005, 2001.  [PUBMED Abstract]
    
    
49. Di Silverio F, D'Eramo G, Lubrano C, et al.: Evidence that Serenoa repens extract displays an antiestrogenic activity in prostatic tissue of benign prostatic hypertrophy patients. Eur Urol 21 (4): 309-14, 1992.  [PUBMED Abstract]
    
    
50. Di Silverio F, Monti S, Sciarra A, et al.: Effects of long-term treatment with Serenoa repens (Permixon) on the concentrations and regional distribution of androgens and epidermal growth factor in benign prostatic hyperplasia. Prostate 37 (2): 77-83, 1998.  [PUBMED Abstract]
    
    
51. Iguchi K, Okumura N, Usui S, et al.: Myristoleic acid, a cytotoxic component in the extract from Serenoa repens, induces apoptosis and necrosis in human prostatic LNCaP cells. Prostate 47 (1): 59-65, 2001.  [PUBMED Abstract]
    
    
52. Wilt T, Ishani A, Mac Donald R: Serenoa repens for benign prostatic hyperplasia. Cochrane Database Syst Rev (3): CD001423, 2002.  [PUBMED Abstract]
    
    

Laboratory/Preclinical Studies

Before the discovery of diethylsylbestrol (DES), warfarin, and indomethacin contamination, PC-SPES appeared to have some efficacy as an antineoplastic agent in laboratory and animal studies. These studies are presented below. Due to the fact that there was no standardization of the composition of PC-SPES or any knowledge of the amount of contamination of each lot used in testing, it is difficult to interpret the data from these studies.

In one study that attempted to measure the effects of the whole PC-SPES mixture versus that of individual herbs of PC-SPES on prostate-specific antigen (PSA) expression and cell growth, LNCaP cells were treated with ethanol extracts of PC-SPES and each of the eight herbs. The PC-SPES mixture reduced cell growth by 72% to 80%, while Dendranthema morifolium (Ramat.) Tzvelev (synonym Chrysanthemum morifolium) (chrysanthemum) produced the highest reduction of the herb group at 85%. Panax pseudo ginseng var. notoginseng Hoo & tseng (Synonym Panax notoginseng [Burkill] F.H.Chen) was next at 80.9% reduction, followed by Glycyrrhiza uralensis Fisch ex DC.(73%). The lowest reduction in cell growth was exhibited by Serenoa repens (Bartr.) Small (14.5%). Scutellaria baicalensis Georgi, Serenoa repens, and Glycyrrhiza uralensis lowered PSA expression, but each of the other herbs increased PSA expression. The ability of individual herbs to reduce PSA expression was not uniform, but the PC-SPES mixture as a whole exhibited a uniform response. The varying results with the individual herbs and the positive response of the cells (i.e., increased cytotoxicity and reduced PSA expression) to the aggregate PC-SPES mixture may suggest that the botanicals in PC-SPES work in concert and that no individual herb can account for the overall effects of the mixture.[1]

In other studies, PC-SPES was found to inhibit clonal growth in three human prostate cancer cell lines: LNCaP, PC-3, and DU-145. Cell cycle analysis showed cell cycle arrest at the G2 phase.[2] Cell proliferation and reduced clonogenicity were observed in cancer cell lines other than those of prostate cancer: human breast carcinoma lines MCF-7 and T47-D, SK-N-MC neuroepithelioma, COLO 38 melanoma, U937 histiomonocytic lymphoma, and HL-60 and MOLT-4 leukemias. Cytotoxic and cytostatic effects of PC-SPES were common to all tumor cell lines tested.[3]

In another study evaluating regulation of PSA expression and androgen receptor (AR) activity, LNCaP prostate cancer cell lines showed downregulation of both proliferating cell nuclear antigen (PCNA) and PSA expression. PSA changes occurred concurrently with the decrease of PCNA. The results suggest that PC-SPES modulates cell growth by changing PCNA expression and may decrease PSA levels indirectly by suppressing AR expression.[4]

None of the studies above indicated lot number or year of manufacture of the PC-SPES used. Therefore, it is not possible to assess the amount of contamination of the mixtures used in the studies or whether the mixtures used were not in fact contaminated.

A 1998 study that evaluated estrogenic activity of extracts of PC-SPES, ginseng (Panax ginseng C.A. Meyer), saw palmetto, DES, and estrone (estradiol -17 beta) in vitro reported on the estrogenic response of ovariectomized CD-1 mice to PC-SPES extract as well as the response to PC-SPES capsules in eight prostate cancer patients who had received previous therapy. [5] This study used four samples of PC-SPES ordered in separate purchases from BotanicLab. No lot numbers were supplied in the study. Lot numbers from October 1996 through July 1998 were later tested for contamination and had DES levels of 114.74 μg/g to 159.27 μg/g, as well as the highest detected levels of indomethacin of the PC-SPES lots tested.[6] In vitro tests of PC-SPES extract or estradiol showed estrogenic activity similar to 1 nM estradiol on estrogen receptor Y253 yeast strain. Transcriptional activation assays in yeast strain PL3 Saccharomyces cerevisiae with ethanolic extract of PC-SPES exhibited estrogen-like effects. In the eight prostate cancer patients, serum testosterone concentrations decreased during the use of PC-SPES and increased within 3 weeks after treatment was discontinued. PSA levels decreased in all eight patients. Side effects in all eight patients were similar to those seen after treatment with estrogen: breast tenderness and loss of libido. One patient had superficial venous thrombosis.

References

1. Hsieh TC, Lu X, Chea J, et al.: Prevention and management of prostate cancer using PC-SPES: a scientific perspective. J Nutr 132 (11 Suppl): 3513S-3517S, 2002.  [PUBMED Abstract]
   
   
2. Kubota T, Hisatake J, Hisatake Y, et al.: PC-SPES: a unique inhibitor of proliferation of prostate cancer cells in vitro and in vivo . Prostate 42 (3): 163-71, 2000.  [PUBMED Abstract]
   
   
3. Ko R, Wilson RD, Loscutoff S: PC-SPES. Urology 61 (6): 1292, 2003.  [PUBMED Abstract]
   
   
4. Hsieh TC, Wu JM: Mechanism of action of herbal supplement PC-SPES: elucidation of effects of individual herbs of PC-SPES on proliferation and prostate specific gene expression in androgen-dependent LNCaP cells. Int J Oncol 20 (3): 583-8, 2002.  [PUBMED Abstract]
   
   
5. 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 339 (12): 785-91, 1998.  [PUBMED Abstract]
   
   
6. 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 94 (17): 1275-81, 2002.  [PUBMED Abstract]
   
   

Animal Studies

By incorporating PC-SPES into the rat diet, researchers conducting an in vivo study showed antitumor effects using a Dunning R3327 rat prostate cancer model. Levels of 0.05% and 0.025% of dietary PC-SPES were fed to the rats over a 6-week period. No toxicity was seen, nor was there a difference in the food intake of the rats during this time. Pulmonary tumors were induced by intradermal injections of MAT-LyLu cells, which are particularly resistant to many forms of treatment. Tumor incidence was inhibited in a dose-dependent manner, and the rate of tumor growth showed the same dose-dependent response. [1,2]

In another study, which used male BNX nu/nu immunodeficient nude mice, PC-SPES was also administered orally, but in suspension. The mice received 300 rad of whole-body irradiation, after which they were inoculated with either PC-3 or DU-145 prostate cancer cell lines. Treatment with PC-SPES began the day after injection. Results showed that PC-SPES suppressed the growth of DU-145 tumors compared to tumor growth in the control group. Cytological analysis showed apoptosis in the treated group that was not apparent in controls.[3]

In two other studies, clinical studies of patients were initiated along with in vitro and in vivo research. The results of these two patient groups are discussed in the Clinical Trials ¹⁰ section. The first study, preceding more extensive research, examined in vitro activity of PC-SPES against LNCaP, LNCaP-bcl-2, PC-3, and DU-145 cells lines. Results showed that PC-SPES was active in suppressing both hormone -sensitive and -insensitive prostate cancer cell lines. In the subsequent study, research was conducted in vitro on the ability of PC-SPES to induce apoptosis in androgen-independent (AI) prostate cancer cell lines, and in vivo on the effect of oral PC-SPES on the growth of xenographed PC-3 tumors in immunodeficient male mice. Mice in the treatment arm—in which treatment was started 1 week after implantation—showed a significant decrease in tumor weight when compared with mice in the control arm. PC-SPES showed activity against both androgen -sensitive and AI prostate cancer in the patients and suppressed tumor growth in AI tumors in mice. Reviewed in [3-5] In both studies, the patients were given capsules manufactured between 1996 and 1999, a time when contamination levels of DES were highest.[6]

Another study in rats demonstrated that PC-SPES (one lot contaminated with DES and one lot without DES) causes some decrease in the activity of a liver enzyme involved in drug metabolism (CYP3A).[7]

References

1. Tiwari RK, Geliebter J, Garikapaty VP, et al.: Anti-tumor effects of PC-SPES, an herbal formulation in prostate cancer. Int J Oncol 14 (4): 713-9, 1999.  [PUBMED Abstract]
   
   
2. Geliebter J, Mittelman A, Tiwari RK: PC-SPES and prostate cancer. J Nutr 131 (1): 164S-166S, 2001.  [PUBMED Abstract]
   
   
3. de la Taille A, 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 164 (4): 1229-34, 2000.  [PUBMED Abstract]
   
   
4. Pirani JF: The effects of phytotherapeutic agents on prostate cancer: an overview of recent clinical trials of PC SPES. Urology 58 (2 Suppl 1): 36-8, 2001.  [PUBMED Abstract]
   
   
5. de la Taille A, Hayek OR, Buttyan R, et al.: Effects of a phytotherapeutic agent, PC-SPES, on prostate cancer: a preliminary investigation on human cell lines and patients. BJU Int 84 (7): 845-50, 1999.  [PUBMED Abstract]
   
   
6. 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 94 (17): 1275-81, 2002.  [PUBMED Abstract]
   
   
7. Wadsworth T, Poonyagariyagorn H, Sullivan E, et al.: In vivo effect of PC-SPES on prostate growth and hepatic CYP3A expression in rats. J Pharmacol Exp Ther 306 (1): 187-94, 2003.  [PUBMED Abstract]
   
   

Clinical Trials

One published randomized cross-over study of patients with androgen-independent (AI) prostate cancer who initially received either 960 mg PC-SPES 3 times a day or 3 mg DES once a day before crossing over to the other regimen when disease progression occurred reports data demonstrating the presence and levels of contaminants in the four lots of PC-SPES used in that trial. The lots were manufactured by BotanicLab (Brea, California). The study was halted and chemical analyses of the lots were performed. The analyses showed that all four lots of PC-SPES contained amounts of DES ranging from 0.1 μg/g to 32.7μg/g, and that one lot contained varying amounts of ethinyl estradiol. The authors concluded that the presence of these contaminants rendered their results inconclusive.[1]

Several nonrandomized clinical studies published between 1999 and 2003 described the results of clinical trials conducted before contaminants had been conclusively identified in PC-SPES lots and before it was known that there was significant variation in naturally occurring active agents, such as baicalein and licochalcone-A, in the lots. These studies, many of which enrolled small numbers of patients, did not identify the source of the lots that were used in the trials, nor did they identify where patients acquired PC-SPES.

In addition to the confounding effects of contaminants on the clinical trial results discussed below, the fact that an optimal dose of PC-SPES remains undetermined and that dose varies among these studies makes it difficult to compare their findings.

In a retrospective study of 23 consecutive patients with AI disease, charts were evaluated for patients’ responses to PC-SPES and the occurrence of any toxicity. There is no report of where the patients acquired their PC-SPES or what lots were used. Patients were all seen between February and November in 1999. Patients ranged in age from 51 to 88 years, with a median age of 70 years. All had previous initial androgen ablation for a period of 6 months to 144 months. Ten patients had received chemotherapy, 13 had not. More than half the patients with AI showed a post- therapy prostate-specific antigen (PSA) decline of 50% or greater. Median time to PSA progression was 6 months. The side effects were similar to those of estrogen therapy: gynecomastia and impotence. Other side effects were nausea/vomiting and diarrhea and to a lesser extent, allergic reactions, leg cramps, and leg swelling.[2]

In a prospective clinical trial of 16 men with stage D3 metastatic prostate cancer in which all patients had failed therapy and had disease progression, the effects of PC-SPES on pain, quality of life, and side effects were assessed. Previous therapy was either orchidectomy or a luteinizing hormone–releasing agonist with or without antiandrogen. Hormonal therapy was continued throughout the trial to avoid the known withdrawal effect of antiandrogen on PSA levels. There was a significant decrease in pain scores such that the 14 patients on analgesics required an average of 40% less analgesics while taking PC-SPES. PC-SPES treatment was associated with improved function and emotional and physical well-being. PSA levels declined significantly after PC-SPES therapy (>50%). Side effects were breast tenderness, deep venous thrombosis, and mild dyspepsia. Reviewed in [3,4]

In a study of 70 patients, 37 with androgen -dependent (AD) disease and 33 with AI disease, the AD cohort was treated with PC-SPES only or after an initial treatment with prostatectomy, radiation, cryotherapy, and/or hormonal therapy. Median duration of PSA response was greater than 57 weeks. All patients in the AD cohort had PSA declines within a range of 80% to 100%, and two patients with bone metastases showed improvement on radiographic analysis. Within the AI cohort, 54% (19 of 35) had a PSA decrease of greater than 50%, with median time to nadir of 10 weeks and a median duration of 18 weeks. Eight of the 16 patients who had received ketoconazole therapy prior to PC-SPES also obtained a decrease of greater than 50% in their PSA values. Testosterone levels within the AD group decreased to castrate levels (<50 ng/mL) in 94% of patients (31 of 33), and libido (25 of 25) and potency (15 of 15) were lost in all patients who entered the study. Side effects were hot flashes, gynecomastia/gynecodynia, and thromboembolic effects in 3 of 70 patients. Although the results of this trial were promising for the treatment of both AI and AD prostate cancer, it is not possible to assess what was responsible for these effects. This trial used PC-SPES from one single lot, but the published study does not indicate the lot number. The research was completed before 2000. No attempt was made to assess the possible contamination of the product.Reviewed in [3,5]

A prospective clinical series assessed the ability of PC-SPES to lower serum PSA levels in 33 prostate cancer patients. The patients had either refused conventional therapy or had failed previous cryosurgery, radiation therapy, and/or hormonal therapy. No overt signs of disease progression were found in any of the patients. At 2 months, PSA levels had decreased by a mean of 52% in 27 of the 31 patients and had increased in two patients. Of the five patients who had hormone - refractory disease, all had decreased serum PSA levels. Reviewed in [3,6]

In a continuation of the previous study, a total of 69 patients with either AI or AD disease were separated into three study groups. Group one (43 patients) had undergone previous therapy, including hormonal; group two (22 patients) developed AI after treatment; and group (four patients) had not undergone previous therapy. The study assessed PC-SPES activity in suppressing PSA levels. Patients were given three capsules of PC-SPES 3 times per day. PSA levels and side effects were observed for 24 months.[7]

In group one, 82% of patients (32 of 39) had a decrease in PSA levels, with 20 patients having a decrease of greater than 50% at 2 months’ follow-up; the decrease lasted for 24 months in two patients. In group two (AI patients), 90% (19 of 21) had a decrease in PSA at their 2-month follow-up, with 66% (14 of 21) having a decrease of greater than 50% in PSA levels. At 24 months, two patients had a decrease of 20% to 50% in pretreatment PSA levels. In group three, 50% (2 of 4) had a decrease of greater than 50% in PSA levels at 2 months, and the remaining two patients had an increase at 2 and 6 months. Eighty-two percent of study patients had a decreased PSA level after 2 months of therapy. Side effects included nipple tenderness (42%), gynecomastia (8%), hot flashes, and deep venous thrombosis.[7]

References

1. 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 22 (18): 3705-12, 2004.  [PUBMED Abstract]
   
   
2. 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 57 (1): 122-6, 2001.  [PUBMED Abstract]
   
   
3. Pirani JF: The effects of phytotherapeutic agents on prostate cancer: an overview of recent clinical trials of PC SPES. Urology 58 (2 Suppl 1): 36-8, 2001.  [PUBMED Abstract]
   
   
4. Pfeifer BL, Pirani JF, Hamann SR, et al.: PC-SPES, a dietary supplement for the treatment of hormone-refractory prostate cancer. BJU Int 85 (4): 481-5, 2000.  [PUBMED Abstract]
   
   
5. 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 18 (21): 3595-603, 2000.  [PUBMED Abstract]
   
   
6. de la Taille A, Hayek OR, Buttyan R, et al.: Effects of a phytotherapeutic agent, PC-SPES, on prostate cancer: a preliminary investigation on human cell lines and patients. BJU Int 84 (7): 845-50, 1999.  [PUBMED Abstract]
   
   
7. de la Taille A, 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 164 (4): 1229-34, 2000.  [PUBMED Abstract]
   
   

Adverse Effects

Adverse effects of PC-SPES treatment were similar to those of hormonal drugs. The percentages indicate the approximate low-to-high range of side effects reported in the studies. It is difficult to compile accurate numbers from all studies reporting side effects because they are not consistently reported. Some studies concatenated categories of side effects, some did not report specific numbers or percentages, and some reported a few side effects while not reporting others. The following references indicate the studies from which the percentages come:

• Gynecomastia (8%–8.7%).[1-6]
• Nipple tenderness (34.8%–100%).[1-7]
• Dyspepsia/nausea (15.7%–21.7%).[2-7]
• Fatigue (8%–17.1%).[1-5]
• Diarrhea (13%–38.6%).[1-5]
• Leg cramps/swelling (2%–68.5%).[1-5]
• Cardiovascular problems/angina (4.3%–7%).[1-5]
• Hot flashes (4.3%–34%).[1-5]
• Decreased libido (6.2%–100%).[5,7]
• Erectile dysfunction (single case report).[8]
• Thromboembolic effects (5%–6.2%).[5,6]

References

1. 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 57 (1): 122-6, 2001.  [PUBMED Abstract]
   
   
2. 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 94 (3): 686-9, 2002.  [PUBMED Abstract]
   
   
3. de la Taille A, 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 164 (4): 1229-34, 2000.  [PUBMED Abstract]
   
   
4. de la Taille A, Hayek OR, Buttyan R, et al.: Effects of a phytotherapeutic agent, PC-SPES, on prostate cancer: a preliminary investigation on human cell lines and patients. BJU Int 84 (7): 845-50, 1999.  [PUBMED Abstract]
   
   
5. 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 18 (21): 3595-603, 2000.  [PUBMED Abstract]
   
   
6. Pfeifer BL, Pirani JF, Hamann SR, et al.: PC-SPES, a dietary supplement for the treatment of hormone-refractory prostate cancer. BJU Int 85 (4): 481-5, 2000.  [PUBMED Abstract]
   
   
7. 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 339 (12): 785-91, 1998.  [PUBMED Abstract]
   
   
8. 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 54 (2): 319-23; discussion 323-4, 1999.  [PUBMED Abstract]
   
   

Substitutes for PC-SPES

No substitutes are available for the original PC-SPES. Although manufacturers are selling supplements purporting to be substitutes, the PC-SPES mixture is patented and cannot be duplicated. There are no published reports of clinical trials of herbal mixtures that claim to be substitutes for PC-SPES. The only company that had a license from the patent holder to manufacture PC-SPES is no longer in business, and the product cannot be legally manufactured in the United States without the patent holder’s permission. PC-SPES is not legally available in the United States.

Overall Level of Evidence for PC-SPES

To assist readers in evaluating the results of human studies of complementary and alternative medicine (CAM) treatments for cancer, the strength of the evidence (i.e., the levels of evidence) associated with each type of treatment is provided whenever possible. To qualify for a level of evidence analysis, a study must:

• Be published in a peer-reviewed scientific journal.
• Report on therapeutic outcome or outcomes, such as tumor response, improvement in survival, or measured improvement in quality of life.
• Describe clinical findings in sufficient detail that a meaningful evaluation can be made.

The lack of consistent composition of PC-SPES due to varying concentrations of contaminants makes it difficult to determine the effects of PC-SPES in humans; therefore, no level of evidence analysis is possible for this treatment. At this time, the use of PC-SPES as a treatment for cancer cannot be recommended outside the context of well-designed clinical trials.

For additional information about levels of evidence analysis, refer to Levels of Evidence for Human Studies of Cancer Complementary and Alternative Medicine ².

Changes to This Summary (09/04/2008)

The PDQ cancer information summaries are reviewed regularly and updated as new information becomes available. This section describes the latest changes made to this summary as of the date above.

General Information ¹¹

An image ⁶ was added to this summary.

More Information

Additional Information about CAM Therapies

• The National Center for Complementary and Alternative Medicine ¹² (NCCAM).
• The National Cancer Institute Office of Cancer Complementary and Alternative Medicine ¹³ (OCCAM).
• CAM on PubMed ¹⁴, a special subset of the PubMed scientific literature database created through a partnership between NCCAM and the National Library of Medicine.

About PDQ

• PDQ® - NCI's Comprehensive Cancer Database ¹⁵

  Full description of the NCI PDQ database.

Other PDQ Summaries

• PDQ® Cancer Information Summaries: Adult Treatment ¹⁶

  Treatment options for adult cancers.

• PDQ® Cancer Information Summaries: Pediatric Treatment ¹⁷

  Treatment options for childhood cancers.

• PDQ® Cancer Information Summaries: Supportive and Palliative Care ¹⁸

  Side effects of cancer treatment, management of cancer-related complications and pain, and psychosocial concerns.

• PDQ® Cancer Information Summaries: Screening/Detection (Testing for Cancer) ¹⁹

  Tests or procedures that detect specific types of cancer.

• PDQ® Cancer Information Summaries: Prevention ²⁰

  Risk factors and methods to increase chances of preventing specific types of cancer.

• PDQ® Cancer Information Summaries: Genetics ²¹

  Genetics of specific cancers and inherited cancer syndromes, and ethical, legal, and social concerns.

• PDQ® Cancer Information Summaries: Complementary and Alternative Medicine ²²

  Information about complementary and alternative forms of treatment for patients with cancer.

Important:

This information is intended mainly for use by doctors and other health care professionals. If you have questions about this topic, you can ask your doctor, or call the Cancer Information Service at 1-800-4-CANCER (1-800-422-6237).

Glossary Terms

An unwanted side effect of treatment.

A drug that triggers an action from a cell or another drug.

Practices used instead of standard treatments. They generally are not recognized by the medical community as standard or conventional medical approaches. Examples of alternative medicine include dietary supplements, megadose vitamins, herbal preparations, special teas, acupuncture, massage therapy, magnet therapy, spiritual healing, and meditation.

A drug that reduces pain. Analgesics include aspirin, acetaminophen, and ibuprofen.

In chemistry, a substance that is similar, but not identical, to another.

A process in which anything complex is separated into simple or less complex parts.

A type of hormone that promotes the development and maintenance of male sex characteristics.

Treatment to suppress or block the production or action of male hormones. This is done by having the testicles removed, by taking female sex hormones, or by taking drugs called antiandrogens. Also called androgen deprivation and androgen suppression.

Describes the ability of tumor cells to grow in the absence of androgens (hormones that promote the development and maintenance of male sex characteristics). Many early prostate cancers require androgens for growth, but advanced prostate cancers are often androgen-independent.

Having to do with reducing inflammation.

A substance that prevents cells from making or using androgens (hormones that play a role in the formation of male sex characteristics). Antiandrogens may stop some cancer cells from growing. Some antiandrogens are used to treat prostate cancer, and others are being studied for this use. An antiandrogen is a type of hormone antagonist.

Having to do with preventing or delaying the development of cancer.

A substance that causes the immune system to make a specific immune response.

A substance that blocks the formation of neoplasms (growths that may become cancerous).

A substance that protects cells from the damage caused by free radicals (unstable molecules made by the process of oxidation during normal metabolism). Free radicals may play a part in cancer, heart disease, stroke, and other diseases of aging. Antioxidants include beta-carotene, lycopene, vitamins A, C, and E, and other natural and manufactured substances.

A type of cell death in which a series of molecular steps in a cell leads to its death. This is the body’s normal way of getting rid of unneeded or abnormal cells. The process of apoptosis may be blocked in cancer cells. Also called programmed cell death.

A benign (noncancerous) condition in which an overgrowth of prostate tissue pushes against the urethra and the bladder, blocking the flow of urine. Also called benign prostatic hyperplasia and BPH.

Pertaining to biology or to life and living things. In medicine, refers to a substance made from a living organism or its products. Biologicals may be used to prevent, diagnose, treat or relieve of symptoms of a disease. For example, antibodies, interleukins, and vaccines are biologicals. Biological also refers to parents and children who are related by blood.

A biological molecule found in blood, other body fluids, or tissues that is a sign of a normal or abnormal process, or of a condition or disease. A biomarker may be used to see how well the body responds to a treatment for a disease or condition. Also called molecular marker and signature molecule.

A drug that helps prevent blood clots from forming. Also called anticoagulant.

Cancer that has spread from the original (primary) tumor to the bone.

Having to do with, or derived from, plants.

Glandular organ located on the chest. The breast is made up of connective tissue, fat, and breast tissue that contains the glands that can make milk. Also called mammary gland.

A term for diseases in which abnormal cells divide without control. Cancer cells can invade nearby tissues and can spread to other parts of the body through the blood and lymph systems. There are several main types of cancer. Carcinoma is cancer that begins in the skin or in tissues that line or cover internal organs. Sarcoma is cancer that begins in bone, cartilage, fat, muscle, blood vessels, or other connective or supportive tissue. Leukemia is cancer that starts in blood-forming tissue such as the bone marrow, and causes large numbers of abnormal blood cells to be produced and enter the blood. Lymphoma and multiple myeloma are cancers that begin in the cells of the immune system. Central nervous system cancers are cancers that begin in the tissues of the brain and spinal cord.

Cancer that begins in the skin or in tissues that line or cover internal organs.

Having to do with the heart and blood vessels.

A detailed report of the diagnosis, treatment, and follow-up of an individual patient. Case reports also contain some demographic information about the patient (for example, age, gender, ethnic origin).

The individual unit that makes up the tissues of the body. All living things are made up of one or more cells.

An increase in the number of cells as a result of cell growth and cell division.

Treatment with drugs that kill cancer cells.

Having to do with the examination and treatment of patients.

A case series in which the patients receive treatment in a clinic or other medical facility.

A type of research study that tests how well new medical approaches work in people. These studies test new methods of screening, prevention, diagnosis, or treatment of a disease. Also called clinical trial.

A type of research study that tests how well new medical approaches work in people. These studies test new methods of screening, prevention, diagnosis, or treatment of a disease. Also called clinical study.

Forms of treatment that are used in addition to (complementary) or instead of (alternative) standard treatments. These practices generally are not considered standard medical approaches. Standard treatments go through a long and careful research process to prove they are safe and effective, but less is known about most types of CAM. CAM may include dietary supplements, megadose vitamins, herbal preparations, special teas, acupuncture, massage therapy, magnet therapy, spiritual healing, and meditation. Also called CAM.

A treatment that is given at the same time as another.

In a clinical trial, the group that does not receive the new treatment being studied. This group is compared to the group that receives the new treatment, to see if the new treatment works.

A currently accepted and widely used treatment for a certain type of disease, based on the results of past research. Also called conventional treatment.

A procedure in which tissue is frozen to destroy abnormal cells. This is usually done with a special instrument that contains liquid nitrogen or liquid carbon dioxide. Also called cryoablation.

Any method that uses cold temperature to treat disease.

Cells of a single type (human, animal, or plant) that have been adapted to grow continuously in the laboratory and are used in research.

Cell-killing.

A synthetic form of the hormone estrogen that was prescribed to pregnant women between about 1940 and 1971 because it was thought to prevent miscarriages. DES may increase the risk of uterine, ovarian, or breast cancer in women who took it. It also has been linked to an increased risk of clear cell carcinoma of the vagina or cervix in daughters exposed to DES before birth. Also called diethylstilbestrol.

Frequent and watery bowel movements.

The things a person eats and drinks.

A product that is added to the diet. A dietary supplement is taken by mouth, and usually contains one or more dietary ingredient (such as vitamin, mineral, herb, amino acid, and enzyme). Also called nutritional supplement.

A synthetic form of the hormone estrogen that was prescribed to pregnant women between about 1940 and 1971 because it was thought to prevent miscarriages. Diethylstilbestrol may increase the risk of uterine, ovarian, or breast cancer in women who took it. It also has been linked to an increased risk of clear cell carcinoma of the vagina or cervix in daughters exposed to diethylstilbestrol before birth. Also called DES.

Cancer that continues to grow or spread.

The molecules inside cells that carry genetic information and pass it from one generation to the next. Also called deoxyribonucleic acid.

The amount of medicine taken, or radiation given, at one time.

Refers to the effects of treatment with a drug. If the effects change when the dose of the drug is changed, the effects are said to be dose-dependent.

Any substance, other than food, that is used to prevent, diagnose, treat or relieve symptoms of a disease or abnormal condition. Also refers to a substance that alters mood or body function, or that can be habit-forming or addictive, especially a narcotic.

A cell line made from human prostate cancer cells that is used in the laboratory to study the way prostate cancer cells grow.

Effectiveness. In medicine, the ability of an intervention (for example, a drug or surgery) to produce the desired beneficial effect.

A protein that speeds up chemical reactions in the body.

An inability to have an erection of the penis adequate for sexual intercourse. Also called impotence.

A form of the hormone estrogen.

A type of hormone made by the body that helps develop and maintain female sex characteristics and the growth of long bones. Estrogens can also be made in the laboratory. They may be used as a type of birth control and to treat symptoms of menopause, menstrual disorders, osteoporosis, and other conditions.

A protein found inside the cells of the female reproductive tissue, some other types of tissue, and some cancer cells. The hormone estrogen will bind to the receptors inside the cells and may cause the cells to grow. Also called ER.

In medicine, a preparation of a substance obtained from plants, animals, or bacteria and used as a drug or in drugs.

A condition marked by extreme tiredness and inability to function due lack of energy. Fatigue may be acute or chronic.

A drug used to reduce the amount of male hormone (testosterone) produced by the body.

A member of a group of substances found in many plants and plant-based foods. Flavonoids have shown antioxidant effects.

Monitoring a person's health over time after treatment. This includes keeping track of the health of people who participate in a clinical study or clinical trial for a period of time, both during the study and after the study ends.

A highly reactive chemical that often contains oxygen and is produced when molecules are split to give products that have unpaired electrons (a process called oxidation). Free radicals can damage important cellular molecules such as DNA or lipids or other parts of the cell.

An herb with a root that has been used in some cultures to treat certain medical problems. It may have anticancer effects.

Treatment that adds, blocks, or removes hormones. For certain conditions (such as diabetes or menopause), hormones are given to adjust low hormone levels. To slow or stop the growth of certain cancers (such as prostate and breast cancer), synthetic hormones or other drugs may be given to block the body’s natural hormones. Sometimes surgery is needed to remove the gland that makes a certain hormone. Also called endocrine therapy, hormone therapy, and hormone treatment.

One of many chemicals made by glands in the body. Hormones circulate in the bloodstream and control the actions of certain cells or organs. Some hormones can also be made in the laboratory.

A sudden, temporary onset of body warmth, flushing, and sweating (often associated with menopause).

The decreased ability of the body to fight infections and other diseases.

In medicine, refers to the inability to have an erection of the penis adequate for sexual intercourse. Also called erectile dysfunction.

In the laboratory (outside the body). The opposite of in vivo (in the body).

In the body. The opposite of in vitro (outside the body or in the laboratory).

The number of new cases of a disease diagnosed each year.

A drug that reduces pain, fever, swelling, and redness. It is also being used to reduce tumor-induced suppression of the immune system and to increase the effectiveness of anticancer drugs. It is a type of nonsteroidal anti-inflammatory drug (NSAID).

Use of a syringe and needle to push fluids or drugs into the body; often called a "shot."

Within the skin. Also called intracutaneous.

Treated with radiation.

A drug that treats infection caused by a fungus. It is also used as a treatment for prostate cancer because it can block the production of male sex hormones.

Research done in a laboratory. These studies may use test tubes or animals to find out if a drug, procedure, or treatment is likely to be useful. Laboratory studies take place before any testing is done in humans.

Cancer that starts in blood-forming tissue such as the bone marrow and causes large numbers of blood cells to be produced and enter the bloodstream.

A white blood cell. Refers to a blood cell that does not contain hemoglobin. White blood cells include lymphocytes, neutrophils, eosinophils, macrophages, and mast cells. These cells are made by bone marrow and help the body fight infection and other diseases.

A ranking system used to describe the strength of the results measured in a clinical trial or research study. The design of the study (such as a case report for an individual patient or a randomized double-blinded controlled clinical trial) and the endpoints measured (such as survival or quality of life) affect the strength of the evidence.

Fat.

A large organ located in the upper abdomen. The liver cleanses the blood and aids in digestion by secreting bile.

Cancer that begins in cells of the immune system. There are two basic categories of lymphomas. One kind is Hodgkin lymphoma, which is marked by the presence of a type of cell called the Reed-Sternberg cell. The other category is non-Hodgkin lymphomas, which includes a large, diverse group of cancers of immune system cells. Non-Hodgkin lymphomas can be further divided into cancers that have an indolent (slow-growing) course and those that have an aggressive (fast-growing) course. These subtypes behave and respond to treatment differently. Both Hodgkin and non-Hodgkin lymphomas can occur in children and adults, and prognosis and treatment depend on the stage and the type of cancer.

Having to do with the breast.

A statistics term. The average value in a set of measurements. The mean is the sum of a set of numbers divided by how many numbers are in the set.

A statistics term. The middle value in a set of measurements.

A form of cancer that begins in melanocytes (cells that make the pigment melanin). It may begin in a mole (skin melanoma), but can also begin in other pigmented tissues, such as in the eye or in the intestines.

The total of all chemical changes that take place in a cell or an organism. These changes make energy and the materials needed for growth, reproduction, and maintaining health. They also help get rid of toxic substances.

Having to do with metastasis, which is the spread of cancer from one part of the body to another.

An organism that can be seen only through a microscope. Microorganisms include bacteria, protozoa, algae, and fungi. Although viruses are not considered living organisms, they are sometimes classified as microorganisms.

The National Cancer Institute, part of the National Institutes of Health of the United States Department of Health and Human Services, is the Federal Government's principal agency for cancer research. The National Cancer Institute conducts, coordinates, and funds cancer research, training, health information dissemination, and other programs with respect to the cause, diagnosis, prevention, and treatment of cancer. Access the National Cancer Institute Web site at http://www.cancer.gov. Also called NCI.

In anatomy, the small raised area in the center of the breast through which milk can flow to the outside.

A drug that decreases fever, swelling, pain, and redness. Also called NSAID.

Closely monitoring a patient's condition but withholding treatment until symptoms appear or change. Also called active surveillance, expectant management, and watchful waiting.

By or having to do with the mouth.

Surgery to remove one or both testicles. Also called orchiectomy.

A specific result or effect that can be measured. Examples of outcomes include decreased pain, reduced tumor size, and improvement of disease.

A mixture of eight herbs that has been sold as a dietary supplement and promoted as a way to keep the prostate healthy and to treat prostate cancer. PC-SPES has been studied in the treatment of prostate cancer, but has been taken off the market in the U.S. because of safety concerns.

PDQ is an online database developed and maintained by the National Cancer Institute. Designed to make the most current, credible, and accurate cancer information available to health professionals and the public, PDQ contains peer-reviewed summaries on cancer treatment, screening, prevention, genetics, complementary and alternative medicine, and supportive care; a registry of cancer clinical trials from around the world; and directories of physicians, professionals who provide genetics services, and organizations that provide cancer care. Most of this information, and more specific information about PDQ, can be found on the NCI's Web site at http://www.cancer.gov/cancertopics/pdq. Also called Physician Data Query.

A publication that contains original articles that have been written by scientists and evaluated for technical and scientific quality and correctness by other experts in the same field.

An estrogen-like substance found in some plants and plant products. Phytoestrogens may have anticancer effects.

An inactive substance or treatment that looks the same as, and is given the same way as, an active drug or treatment being tested. The effects of the active drug or treatment are compared to the effects of the placebo.

Refers to a clinical study in which the control patients receive a placebo.

A large carbohydrate molecule. It contains many small sugar molecules that are joined chemically. Also called glycan.

A doctor's order for medicine or another intervention.

In medicine, the course of a disease, such as cancer, as it becomes worse or spreads in the body.

Multiplying or increasing in number. In biology, cell proliferation occurs by a process known as cell division.

An aggressive (fast-growing) type of acute myeloid leukemia in which there are too many immature blood-forming cells in the blood and bone marrow. It is usually marked by an exchange of parts of chromosomes 15 and 17. Also called acute promyelocytic leukemia and APL.

In medicine, a study or clinical trial in which participants are identified and then followed forward in time.

A gland in the male reproductive system. The prostate surrounds the part of the urethra (the tube that empties the bladder) just below the bladder, and produces a fluid that forms part of the semen.

Cancer that forms in tissues of the prostate (a gland in the male reproductive system found below the bladder and in front of the rectum). Prostate cancer usually occurs in older men.

A substance produced by the prostate. It may be found in higher levels in the blood of men who have prostate cancer, benign prostatic hyperplasia, infection or inflammation of the prostate. Also called PSA.

An operation to remove part or all of the prostate. Radical (or total) prostatectomy is the removal of the entire prostate and some of the tissue around it.

A small, positively charged particle of matter found in the atoms of all elements. Streams of protons generated by special equipment can be used for radiation treatment.

A substance produced by the prostate. It may be found in higher levels in the blood of men who have prostate cancer, benign prostatic hyperplasia, infection or inflammation of the prostate. Also called prostate-specific antigen.

Having to do with the lungs.

The overall enjoyment of life. Many clinical trials assess the effects of cancer and its treatment on the quality of life. These studies measure aspects of an individual’s sense of well-being and ability to carry out various activities.

Energy released in the form of particle or electromagnetic waves. Common sources of radiation include radon gas, cosmic rays from outer space, medical x-rays, and energy given off by a radioisotope (unstable form of a chemical element that releases radiation as it breaks down and becomes more stable).

The use of high-energy radiation from x-rays, gamma rays, neutrons, protons, and other sources to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy), or it may come from radioactive material placed in the body near cancer cells (internal radiation therapy). Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that travels in the blood to tissues throughout the body. Also called irradiation and radiotherapy.

A study in which the participants are assigned by chance to separate groups that compare different treatments; neither the researchers nor the participants can choose which group. Using chance to assign people to groups means that the groups will be similar and that the treatments they receive can be compared objectively. At the time of the trial, it is not known which treatment is best. It is the patient's choice to be in a randomized trial.

A molecule inside or on the surface of a cell that binds to a specific substance and causes a specific physiologic effect in the cell.

Cancer that does not respond to treatment. The cancer may be resistant at the beginning of treatment or it may become resistant during treatment. Also called resistant cancer.

A treatment plan that specifies the dosage, the schedule, and the duration of treatment.

Cancer that does not respond to treatment. The cancer may be resistant at the beginning of treatment, or it may become resistant during treatment. Also called refractory cancer.

In medicine, an improvement related to treatment.

A study that compares two groups of people: those with the disease or condition under study (cases) and a very similar group of people who do not have the disease or condition (controls). Researchers study the medical and lifestyle histories of the people in each group to learn what factors may be associated with the disease or condition. For example, one group may have been exposed to a particular substance that the other was not. Also called case-control study.

The clear liquid part of the blood that remains after blood cells and clotting proteins have been removed.

A problem that occurs when treatment affects healthy tissues or organs. Some common side effects of cancer treatment are fatigue, pain, nausea, vomiting, decreased blood cell counts, hair loss, and mouth sores.

In statistics, describes a mathematical measure of difference between groups. The difference is said to be significant if it is greater than what might be expected to happen by chance alone. Also called statistically significant.

The extent of a cancer in the body. Staging is usually based on the size of the tumor, whether lymph nodes contain cancer, and whether the cancer has spread from the original site to other parts of the body.

Adding nutrients to the diet.

A hormone made mainly in the testes (part of the male reproductive system). It is needed to develop and maintain male sex characteristics, such as facial hair, deep voice, and muscle growth. Testosterone may also be made in the laboratory and is used to treat certain medical conditions.

Having to do with treating disease and helping healing take place.

Treatment.

The formation or presence of a thrombus (blood clot) inside a blood vessel.

Radiation therapy to the entire body. It is usually followed by bone marrow or peripheral stem cell transplantation.

An abnormal mass of tissue that results when cells divide more than they should or do not die when they should. Tumors may be benign (not cancerous), or malignant (cancerous). Also called neoplasm.

Fluid containing water and waste products. Urine is made by the kidneys, stored in the bladder, and leaves the body through the urethra.

The small, hollow, pear-shaped organ in a woman's pelvis. This is the organ in which a baby grows. Also called womb.

A drug that prevents blood from clotting. It belongs to the family of drugs called anticoagulants (blood thinners).