Evaluation of PC-SPES in Prostate Cancer Patients
Evaluation of PC-SPES in Prostate Cancer Patients
ABSTRACT & COMMENTARY
Synopsis: A Phase II study of the herbal supplement PC-SPES was performed with 33 androgen-dependent prostate cancer (ADPCa) patients and 37 androgen-independent prostate cancer (AIPCa) patients. All of the ADPCa patients achieved a PSA decline of greater than 80%, with a median duration of this response being greater than 57 wk. Nineteen (54%) of 35 AIPCa patients had a PSA decline of greater than 50%, with a median time to PSA progression of 16 wk (range, 2-69+ wk). Additional measures of response to PC-SPES, including bone scan improvement and resolution of a bladder mass seen on pelvic CT, were reported. Severe toxicities included pulmonary embolism (n = 3) and allergic reactions (n = 3). PC-SPES has activity in the treatment of both ADPCa and AIPCa with acceptable toxicity. Comparative studies of PC-SPES with more conventional means of antigen deprivation merits consideration.
Source: Small EJ, et al. J Clin Oncol 2000;18: 3595-3603.
Pc-spes is an herbal supplement that has been used as a complementary or alternative medical therapy by patients with prostate cancer.1 Initial reports have identified the estrogenic nature of PC-SPES, and clinical activity has been reported in a small number of prostate cancer patients.1 Preclinical studies have identified antiproliferative effects of PC-SPES against prostate cancer cells.2 Since PC-SPES has received wide use in the community, a Phase II study was designed to evaluate efficacy and toxicity of PC-SPES in a prospective controlled study for prostate cancer patients (ADPCa and AIPCa).
Small and colleagues report results of a Phase II study involving 33 patients with ADPCa and 37 patients with AIPCa who received treatment PC-SPES at a target dose of nine capsules daily. The patients received 320 mg capsules, 1 orally t.i.d. for one week. If there were no apparent adverse events, the dose was escalated to two capsules orally t.i.d. for one week. A further escalation to a maximal dose of three capsules orally t.i.d. was permitted if no apparent adverse events occurred. This final dose was determined empirically based on a regimen commonly used in the community. The median age of patients with ADPCa was 64 (range, 48-86) and the median age of patients with AIPCa was 68 (range, 43-89). Baseline Karnofsky performance status (KPS) of both groups of patients was excellent, with a median KPS of 100 in the ADPCa patients (range, 90-100) and a median KPS of 90 in the AIPCa patients (range, 70-100).
One hundred percent of the ADPCa patients receiving PC-SPES had a greater than 50% PSA decline, and 54% of the AIPCa patients had a PSA decline of more than 50%. Additional measures of antitumor response were available in some of the patients and included bone scan improvement (2 of 2 ADPCa patients and 2 of 25 AIPCa patients) and soft tissue response measured by CT scan (1 of 1 patient ADPCa patient and 0 of 1 AIPCa patient). Endocrine changes included a decrease in testosterone level to less that 50 ng/ml in 97% (31/32) of the ADPCa patients, and 100% of the evaluated ADPCa patients reported a libido decline with therapy (24/24), potency decline with therapy (15/15), and gynecomastia/gynecodynia (32/32).
Severe toxicities (grade 4) included three patients with pulmonary embolism, one patient with elevated triglycerides and one patient with renal failure (the renal failure was considered unrelated to PC-SPES). The following grade 3 toxicities also occurred: allergic reactions (1 patient; 1.4%), atrial arrhythmia (1 patient; 1.4%), congestive heart failure (2 patients; 2.9%), diarrhea (2 patients; 2.9%), hyperglycemia (1 patient; 1.4%), leg cramps (1 patient; 1.4%), elevation in AST/ALT (1 patient; 1.4%), and elevated triglycerides (1 patient; 1.4%). The episodes of congestive heart failure were considered unrelated to PC-SPES. Common grade 1 and 2 toxicities included leg cramps, diarrhea, elevated cholesterol, constipation, fatigue, hyperglycemia, nausea, and elevated triglycerides. Many patients experienced gynecomastia/gynecodynia. Overall, treatment with PC-SPES was considered reasonably well tolerated. The primary severe toxicities were thromboembolic events. The duration of PC-SPES treatment at the time of pulmonary embolism was seven months in two patients and two weeks in the third patient.
Comment by Mark R. Albertini, MD
Several complimentary and alternative medical therapies are being used by cancer patients.3 While most of these treatments have unknown (if any) benefit, some may have antitumor properties. Thus, identification of potential antitumor properties of some of these treatments may be informative. In addition, some of these treatments may present medical risks that should be identified.4 Small et al proceeded with this Phase II study of PC-SPES due to its widespread use in the community and due to preliminary preclinical and clinical results suggesting antitumor activity.
This small Phase II study demonstrates androgen deprivation and subsequent antitumor effects in patients with androgen-dependent prostate cancer receiving PC-SPES. However, alternate safe conventional therapies are currently available for these patients.5 Small et al also report antitumor activity of PC-SPES for patients with androgen-independent prostate cancer. Since current therapies for these patients provide limited benefit,6-7 additional evaluation appears reasonable. Comparative studies will be needed to determine the relative activity of PC-SPES as a second- or third-line treatment for patients with androgen-independent prostate cancer.
The dose and schedule used in this study was empiric and was based on a dose and schedule of PC-SPES commonly used in the community. Additional clinical evaluation, with attention to dose and schedule, may improve the therapeutic potential of this treatment. In addition, use of PC-SPES in combination with other therapies could be considered. The need for a careful evaluation of unconventional complementary treatments that patients are taking is also emphasized by this study. As patients on clinical studies may also be taking complementary medications, this information is essential to appropriately evaluate both antitumor effects and toxicities of novel agents being tested in clinical studies.
References
1. DiPaola RS, et al. N Engl J Med 1998;339:785-791.
2. Kubota T, et al. Prostate 2000;42:163-171.
3. Eisenberg DM, et al. N Engl J Med 2000;328:246-252.
4. Angell M, Kassirer JP. N Engl J Med 1998;339: 839-841.
5. Eisenberger M, et al. N Engl J Med 1998;339: 1036-1042.
6. Small EJ, Vogelzang NJ. J Clin Oncol 1997;15: 382-388.
7. Smith DC, et al. Urology 1998;52:257-260.
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