BIRMINGHAM CENTRE FOR CHINESE MEDICINE
245 Alcester Road South, Kings Heath, Birmingham B14 6DT
Tel: 0121-441 2757
PROSTATE CANCER AND CHINESE HERBAL MEDICINE: THE CASE OF PC-SPES
INTRODUCTION
A great deal of research has been conducted, especially in China, in the use of Chinese herbal medicine in the treatment of cancer. This is for the most part laboratory research suggesting that a number of Chinese herbs have anti-cancer properties. One area in which orthodox clinical trials have been conducted is in the field of prostate cancer. This is a result of the intense interest generated by a formula called PC-SPES, developed in the United States in the mid-1990s. This product was later withdrawn from the market, although research indicated that it had helped very many prostate cancer sufferers. The story behind this, together with the use of a version of the formula for a patient at the Birmingham Centre for Chinese Medicine, is told below.
Prostate cancer is the most commonly diagnosed cancer in men in the UK and, after lung cancer, the second most common cause of cancer mortality. A range of conventional treatments is available, depending on grade and stage of tumour and levels of prostate specific antigen (PSA). Currently, approaches include observation, prostatectomy, radiation (external beam or brachytherapy [insertion of radioactive seeds into the prostate]), orchidectomy (removal of testicles), and varieties of hormonal treatment. The benefits are unclear. While in many cases there is no recurrence after treatment, prostate cancer is generally slow-growing and can develop without affecting normal lifespan, even if left untreated. On the other hand, with more advanced forms, the outlook is poor and conventional approaches have not improved it. Furthermore, the treatments are associated with a number of severe adverse effects, in particular incontinence, loss of libido and impotence, disturbed bowel function and menopausal symptoms.
Into this difficult environment there stepped a product called PC-SPES (standing for Prostate Cancer-Hope), which became available on the US market in 1996. PC-SPES quickly established a reputation for the help that it could give to sufferers from prostate cancer, though it too came with some side-effects. It was labelled as containing extracts of eight herbs; for most of these herbs there had been reports of activity against cancer cells. [1]
Isatis Indigotica Da Qing Ye (or Ban Lan Gen)
Glycyrrhiza Glabra/Uralensis Gan Cao
Panax Pseudo-Ginseng San Qi
Ganoderma Lucidum Ling Zhi
Scutellaria Baicalensis Huang Qin
Chrysanthemum Morifolium Ju Hua
Rabdosia Rubescens Dong Ling Cao
Serenoa Repens/Serrulata Saw Palmetto
PC-SPES was produced by BotanicLab in California, and was available in capsuled powdered form through mail or telephone order, internet sales, distributors and health care professionals. The 'founders and patent-holders' of the company were John Chen and Sophie Chen, and reports indicate that the ingredients were brought in from China and blended by BotanicLab [2].
TRIALS OF PC-SPES
Unusually for a herbal product, PC-SPES caused excitement in the medical world, especially in the USA, and became the subject of a number of clinical trials the results of which were published in the orthodox medical press. These suggested that the formula could play a valuable role in the treatment of advanced prostate cancer. An early, very small study by DiPaolo et al, assessed the activity of PC-SPES in eight patients with hormone-sensitive disease by measuring PSA and testosterone levels before and after treatment (while androgen-blocking therapy was withdrawn). Both PSA and testosterone showed marked declines, though accompanying symptoms included breast tenderness and loss of libido, and there was one case of thrombosis. The authors concluded that the formula had a strong oestrogenic effect, which must be coming from plant materials, since a number of tests (high-performance liquid chromotography, gas chromotography and mass spectrometry) had failed to identify the presence of oestradiol, oestrone or diethylstilboestrol. [3]
Research that followed included a study by Pfeifer et al, involving 16 men with advanced disease for whom hormone-blocking therapy had failed. They took PC-SPES for 5 months, remaining however on hormonal therapy throughout the study, because of the known effect of withdrawal on PSA levels. Very good improvements were recorded in pain ratings and quality of life measures, and most patients responded with a more than 50% reduction in PSA levels.[4] Side-effects were similar to those described by DiPaola et al, though breast tenderness was less common (50% of patients, compared with 100% in the DiPaola study). However, Pfeifer et al questioned the inference that the power of PC-SPES must be due mainly to its oestrogenic effects. If this were the case, then several of the patients in the DiPaola study, who had not previously responded to oestrogen therapy, would not have responded to PC-SPES either. The authors suggested instead, on the basis of other published reports, that there were possible gene effects promoting apoptosis, and an immune-enhancing function. [5] [6] The conclusion was that 'PC-SPES significantly reduces PSA levels and the pain of metastatic disease, thereby improving patients' quality of life without the detrimental side-effects seen with other drug regimens. With no cure currently available for these patients, maintaining a good quality of life is a realistic therapeutic goal that can be achieved with the dietary supplement PC-SPES.' [4]
Alexander de la Taille et al evaluated the efficacy of PC-SPES in 69 patients with prostate cancer. 82% had decreased PSA levels after two months of treatment, 78% after 6 months, and 88% after 12 months. Side effects included nipple tenderness in 42%, breast enlargement in 8%, hot flushes in 7%, while one patient developed thrombosis. An in vitro study was also carried out, confirming that PC-SPES could induce apoptosis in hormone-sensitive and hormone-insensitive prostate cancer. The authors concluded that 'PC-SPES has potent estrogenic activity' and that its effects were 'similar to those of diethylstilbestrol in terms of PSA decrease and side-effects observed'. However, the fact that it had a clinical effect on patients with hormone-resistant disease suggested that oestrogen-like activity was not the only mechanism of action. [7]
A further much-publicised study by E. Small et al assessed PC-SPES treatment of 70 patients, comprising two groups with androgen-dependent (33) and androgen-independent (37) prostate cancer. Again there were marked declines in PSA and testosterone levels, and in certain cases bone scans improved. Breast enlargement and tenderness, leg cramps and diarrhoea were frequently reported, and there were three thromboembolic events during the trial. The conclusion was that PC-SPES 'seems to have activity in the treatment [of both androgen-dependent and androgen-independent] prostate cancer and has acceptable toxicity'. [1] This study was followed by a randomised trial by Small et al to compare the effects of oestrogen (dyethylstilboestrol) and PC-SPES on patients with androgen-independent prostate cancer. As the trial progressed, the results were encouraging for PC-SPES, with 45% of the PC-SPES group and only 21% of the DES group having a 50% or more decline in PSA. However, the trial was abandoned in early 2002. [2]
WITHDRAWAL FROM THE MARKET
In the summer of 2001, as a result of queries by some patients arising from changes in response to PC-SPES, it was found that some batches of PC-SPES contained undeclared pharmaceutical ingredients, in particular small quantities of the the hormonal drug diethylstilboestrol (DES) [2]. Tests also showed that some batches of PC-SPES contained warfarin, while SPES (another BotanicLab product sold for other forms of cancer) contained alprazolam (a sedative drug with possible analgesic properties). In February 2002 the US Federal Drug Administration therefore told consumers and practitioners to stop using these products. [2]
Subsequently a study by M. Sovak et al, using a variety of advanced tests, showed that there had been a number of different versions of PC-SPES on the market. Batches manufactured from 1996 to mid-1999 contained indomethacin (range = 1.07-13.19 mg/g) and diethylstilboestrol (range = 107.28-159.27 micro g/g). In lots manufactured after mid-1999, there were gradual declines in indomethacin (from 1.56 to 0.70 mg/g) and diethylstilboestrol (from 46.36 to 0.00 micro g/g), and also a decline in total phytosterols (from 0.586 to 0.085 mg/g). Warfarin was identified for the first time in lots manufactured after July 1998 (range = 341-560 micro g/g). [9]
FURTHER RESEARCH
Following the withdrawal of PC SPES, the results of a further study, led by Michael Bonham of the Fred Hutchinson Cancer Research Centre in Seattle, were published in Cancer Research. This study used DNA analysis to identify changes in prostate cancer cells exposed to PC-SPES (carefully checked for purity) and to oestrogenic agents including DES. The authors concluded that a 'comparison of gene expression profiles resulting from these treatments indicates that PC-SPES exhibits activities distinct from those attributable to diethylstilbestrol and suggests that alterations in specific genes involved in modulating the cell cycle, cell structure and androgen response may be responsible for PC-SPES cytotoxicity.' This again raised doubts about how far the effects of PC-SPES were due to its oestrogenic properties. [10]
USING UNADULTERATED PC-SPES
In 2002 the Birmingham Centre for Chinese Medicine was approached by a doctor with prostate cancer who had been buying PC-SPES from a supplier in New York. He had experienced considerable benefit from it, but following withdrawal of PC-SPES from the market, this source had dried up. The patient did not believe that the benefits he had experienced were due to do with the pharmaceutical ingredients that had been found. The Centre agreed to try to help, and as a result the patient is taking a version of the eight-herb formula described above.
The patient had begun his treatment with standard androgen-blocking drugs which produced marked and disruptive menopausal side effects. These included hot flushes and sweating, itching and aching legs, which did not respond to conventional therapy. They were however virtually eliminated when he was on PC-SPES, though there had been some oestrogenic symptoms of tender breast swelling. Apart from this he felt extremely well. When PC-SPES was withdrawn, all the unpleasant menopausal symptoms returned. The version of the formula that he is taking now is evidently helping, since the menopausal symptoms are greatly alleviated and only moderate hot sweaty flushes remain. There is no breast enlargement or tenderness. Concerning the relief of the side-effects of the androgen-blockade treatment, the verdict is so far so good. On the basis of this experience, and given that research also suggests that the formula has the ability to encourage apoptosis and inhibit the cancer, the intention is to continue with the Chinese medicine treatment for the foreseeable future.
IN CONCLUSION
Since PC-SPES had given relief to thousands of patients, and was possibly helping to limit the cancer itself, the withdrawal of PC-SPES was a big blow to those who had benefitted from it. The suppliers of the product in the United States have much to answer for, since it is clear that proper quality controls were not being used. However, the irony is that the addition of pharmaceuticals in some batches of PC-SPES, though it may have magnified the oestrogenic effects of the formula, may not have contributed much to its benefits. This is suggested by the changes experienced by patients with hormone-insensitive cancer, and by the research indicating the presence of non-oestrogenic mechanisms. Research in this area is continuing despite the setback with PC-SPES, and results will be reported on this page.
REFERENCES
[1] E.Small et al 'Prospective trial of the herbal supplement PC-SPES in patients with progressive prostate cancer' Journal of Clinical Oncology Vol 18, no.21 (Nov 1), 2000: 3595-3603]
[2] Jacquie Strax, 'FDA Alerts Consumers and Urologists to Stop Using PC SPES and SPES', PSA Rising Magazine, in www.psa-rising.com, 8 Feb 2002
[3] RS DiPaola et al, 'Clinical and Biologic Activity of an Estrogenic Herbal Combination (PC SPES) in Prostate Cancer', New England Journal of Medicine, Vol 339, No 12 (Sep 17), 1998, 785-791
[4] BL Pfeifer et al, 'PC-SPES, a Dietary Supplement for the Treatment of Hormone-Refractory Prostate Cancer' BJU International, Vol 85, (2000), 481-485
[5] Halicka HD et al, 'Apoptosis and cell cycle effects induced by extracts of the Chinese herbal preparation PC-SPES' International Journal of Oncology 1997; 11:437
[6] Hsieh T et al, 'Induction of apoptosis and down-regulation of bcl-6 in Mutu I cells treated with ethanolic extracts of the Chinese herbal preparation PC-SPES' International Journal of Oncology 1998;13:1199
[7] Alexandre de la Taille et al, 'Herbal Therapy PC-SPES: In Vitro Effects and Evaluation of its Efficacy in 69 Patients with Prostate cancer', Journal of Urology Vol 164, no 4, Oct 2000
[8] J.Strax, 'PC SPES Trial halted' PSA Rising, Feb 5, 2002.
[9] M. Sovak et al, 'Herbal composition PC-SPES for management of prostate cancer: identification of active principles', Journal of the National Cancer Institute 2002, 94(17):1275-81 (testing of ingredients was by high-pressure liquid chromatography, proton nuclear magnetic resonance, gas chromatography/mass spectrometry, and mass spectra analysis)[10] M.Bonham et al, 'Molecular Effects of Activity Pathways in Prostate Carcinoma', Cancer Research 62, 3920-3924, July 15, 2002