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]
   
   

Glossary Terms

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

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

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.

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.

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

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.

Treatment with drugs that kill cancer cells.

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 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.

Frequent and watery bowel movements.

Cancer that continues to grow or spread.

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

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.

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.

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).

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

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.

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.

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

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

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

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

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.

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

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.

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 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.

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.

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.

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.

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

Treatment.

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