Various approaches to hormonal treatment of prostate carcinoma are discussed. Eighty-one patients with prostatic carcinoma, eight with stage B, nine with stage C, and 64 with stage D disease, were treated subcutaneously daily for 3 months with the LH-RH agonist D-Trp-6-LH-RH (Decapeptyl) in order to evaluate the incidence of remissions according to WHO recommendations for oncologic trials. The findings were compared to those obtained with other hormonal therapies of prostatic carcinoma according o the statistical method of 'expected response rate' as adapted by Lee and Wesley for phase II trials. Treatment with D-Trp-6-LH-RH greatly reduced serum LH and testosterone levels without raising serum prolactin. After 1-2 weeks of therapy, there was relief of subjective symptoms and a reversal of the signs of prostatism as well as a marked decrease in bone pain. At 90 days 52 patients had complete relief of prostatism and 21 had only mild signs and symptoms. Seventy patients were experiencing no bone pain and an additional six had only mild pain. Prostatic size, evaluated by rectal examination and transabdominal ultrasonography, reverted to normal in 26.4% of patients (complete remission) and was reduced by more than 50% in an additional 17.6% (partial remission), the overall rate of complete plus partial regression of prostatic enlargement being 44%. Scans showed a major improvement of bone lesions in 14.8% of cases. This response increased to 37% after more than 6 months of follow-up. Prostatic acid phosphatase levels were decreased by more than 50% in 61% of the patients, but this test appears to be a less valid marker than the lipid-associated sialic acid (LASA). The increase in LASA before treatment and a reduction after treatment can frequently be correlated with the objective volume of the neoplasms. No flare-up of the disease was encountered, and there were no side effects except for impotence. Statistical analyses of results by the method of Lee and Wesley indicated that the incidence of complete and partial regression (CR and PR) observed with D-Trp-6-LH-RH was not significantly different from that recorded in previous studies for another LH-RH analog, Buserelin. However, CR and PR obtained with D-Trp-6-LH-RH (44%) were significantly higher than with subcapsular orchiectomy (22%). Hormonal effects and some other actions of D-Trp-6-LH-RH were compared and contrasted with those produced by castration, estrogens, antiandrogens, and progestogens. The treatment of prostatic carcinoma with D-Trp-6-LH-RH avoids the cardiovascular and mannotropic side effects of estrogens, hepatic effects of some antiandrogens, and psychological impact of orchiectomy. There is still no evidence that the combination of LH-RH analogs and small doses of antiandrogens offers an advantage over the use of LH-RH agonists alone. Our findings indicate that currently LH-RH analogs may be the method of choice for the treatment of advanced prostatic carcinoma. We also suggest that hormonal therapy with LH-RH agonists can be combined with chemotherapy, the initial response to which might be potentiated by an early and transitory increase in testosterone levels. Our results warrant continuation of large-scale clinical trials with LH-RH agonists to establish their long-term efficacy.
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