PCa Commentary
 

Hormone News - (Actually, Anti-Hormone News) (Nov 2003)

SOMETHING GOOD IS HAPPENING. "Since the introduction of testing for PSA, the incidence of prostate cancer has increased, whereas the mortality from this disease has decreased" from a death rate of 26.4/100,000 to 21.5/100,000, a decline of 2.6% per year (Albertson, "The Prostate Cancer Conundrum", JNCI, July 2, 2003). Why? Whether this is due to PSA screening, better local control, or the more widespread use of hormone intervention is unclear. Cooperberg (ibid) cites the marked increase in androgen deprivation therapies at all risk levels of prostate cancer and highlights the survival advantage of its early use in the Bolla trial involving XRT in high risk PC patients, and Messing trial in N1 patients post RP. An even more forceful endorsement of the early use of androgen deprivation intervention came from the prominent biostatistician, Sir Richard Peto, PhD, at the European Cancer Conference (abst. 328), September 2003, reporting on the worldwide collaborative meta-anaylses of the randomized trials of hormonal treatments for early breast cancer and non-metastatic prostate cancer. In both diseases there was a highly significant decrease (P=<0.00001) in cancer specific mortality over the past 10 years and this was seen with little effect on mortality from other causes. The prostate trials were composed of a total of 3000 men with non-metastatic PC and compared immediate versus deferred hormonal treatment. Their analysis contends that the earlier application of hormone intervention (as opposed to "delayed") was associated with a 12% lower mortality. Overall, in the last ten years, Dr. Peto reported there was a 33% decline in risk of prostate cancer deaths in the USA resulting from earlier detection, local control, and hormone therapy.

ALTERNATIVES TO LUPRON AND ZOLADEX: AN UPATE

CASODEX 150 mg: Some men decline the appropriate recommendation for androgen deprivation because of the concern about the "side effects" that accompany the testosterone lowering resulting from from LHRH agonists. In Europe a common form of hormone intervention is 150 mg/day of Casodex, a drug that actually raises testosterone while lowering the intracellular dihydrotestosterone by 90%. The regimen combats the progressive loss of bone density associated with LHRH agonists. Abstract #83 in the Proceedings of the 45th Annual ASTRO Meeting ("Bicalutamide 150 mg as Adjuvant to Radiotherapy Significantly Increases Progression-Free Survival [PFS] in Early Prostate Cancer") presents an interim report at 3 years of the Early Prostate Cancer (placebo controlled) Trial in which the drug was associated with a 42% comparative prolongation of PSA-PFS. The benefit was clearest for patients at greatest risk for disease progression. Gynecomastia was the major side effect, and nipple irradiation should precede therapy. Astra-Zeneca, the drug manufacturer, has recently cautioned about a slight increase in cardiac events from this dose, a dose not currently approved for use in the USA.

PROSCAR (finasteride)/ EULEXIN or CASODEX: Proscar 5 mg/day combined with either Eulexin 250 mg/tid or Casodex 50 mg/day represents another alternative to LHRH agonists. The question of whether an LHRH agonist or castration could "salvage" men upon failure from one of these combinations was addressed in the article, "Finasteride and Flutamide Therapy in Patients with Advanced Prostate Cancer: Response to Subsequent Castration and Long-Term Follow-up" (UROL, July 2003, p.99). The initial fall in PSA from the F/F combination was 94%, gynecomastia was mild to moderate, erectile function remained intact in 55% of men whose function was normal at baseline, and in 25% (5 of 20) the disease remained under control at 7 years. Twelve men who subsequently failed initial F/F treatment were then treated with Lupron (11) or castration. All experienced a >50% decline in PSA (mean 89%, range 62% - 100%). "Castration [with Lupron] appears to have a shorter duration of response than if started initially, but the overall period of hormonally sensitive prostate cancer is more than 4 years."

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