PC-SPES: Hope or Hype?

Herbal medicines have always held an attraction for patients. Often used unmodified, or only slightly modified from their natural state, they are considered by many to be a pure, safe, and reasonable alternative to traditional, potentially more toxic treatments. Approximately 25% of prescription medicines are derived from plants. Examples in oncology include morphine, vinca alkaloids, and the taxanes. From a regulatory perspective, herbal products fall under the Dietary Supplement Health Education Act, enacted in 1994. Herbals are considered safe unless they “present a significant risk of illness or injury” under the conditions or use recommended in the labeling. While many herbal supplements are safe, there can be interactions with prescription medicines. An example is St John’s wort (hypericum perforatum), the agent of choice for depression in Europe, outselling Prozac 20-fold. St John’s wort is an inducer of cytochrome P-450, which can increase the clearance of irinotecan by 42%, thereby decreasing efficacy. 1 It also induces p-glycoprotein, enhancing drug efflux of the taxanes, anthracyclines, and vinca alkaloids, thereby potentially decreasing efficacy. It has long been recognized that there can be great inconsistency among what appear to be identical natural substances. Examples include different vintages of wine, and different teas or coffees. Growing conditions, time of harvest, conditions of handling, and storage all potentially introduce variability in potency that might affect efficacy and toxicity. Caveat emptor. PC-SPES is a proprietary formulation that was marketed by Botanic Lab (Brea, CA) 2 from 1966 through 2002. PC stands for prostate cancer, and spes is Latin for hope. Each capsule of PC-SPES contains 320 mg of eight herbs in a proprietary formulation. The recommended dose for “prostate health” is three to six capsules per day on an empty stomach. The 2002 cost was $108 for a bottle of 60 capsules. The eight herbs included in PC-SPES are listed in Table 1. In preclinical studies, most of these agents have in vitro properties ranging from stimulation of natural killer-cell activity to growth inhibitory effects across a range of cell lines. Other components exhibit estrogenic activity (Isatis indigotica, Glycyrrhiza uralensis) or inhibit 5-alpha reductase (Seronoa repens). 3 The clinical activity of PC-SPES had been previously demonstrated in four small phase II studies in patients with androgen-insensitive prostate cancer (AIPC). 4-7 The response rate, as measured by a prostate-specific antigen (PSA) decline of 50%, ranged from 50% to 81%. In one phase II study of patients with both androgen-sensitive and androgen-insensitive prostate cancer, PC-SPES, at a dose of nine pills per day, decreased the PSA by 50% in 100% of androgen-dependent tumors and 54% of androgeninsensitive tumors. Interestingly, eight of 16 patients with tumors who progressed on adrenal androgen suppression, a very difficult group of patients to treat, had a PSA decline of 50%. In this and other studies, gynecomastia was near universal (90% to 97%); leg cramps were common (69%) and nausea and vomiting occurred in 14%, and thromboembolism occurred in approximately 5% of patients. 6