Phase II trial with D‐Trp‐6‐LH‐RH in prostatic carcinoma: Comparison with other hormonal agents

Abstract

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 to 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.(ABSTRACT TRUNCATED AT 400 WORDS)

Somatostatin analogs as adjuncts to agonists of luteinizing hormone-releasing hormone in the treatment of experimental prostate cancer.

“…The suppression of pituitary and gonadal functions that occurs after chronic administration of LH-RH agonists produces a state of chemical castration and provides the current approach for the treatment of prostate cancer and other sex hormone-dependent tumors (1,2,4,5,33 (4,5,33,35). One of the approaches for improving the therapeutic response and its duration could be based on combining hormonal therapy with chemotherapy (4,5,36).…”

Combination of a long-acting delivery system for luteinizing hormone-releasing hormone agonist with Novantrone chemotherapy: increased efficacy in the rat prostate cancer model.

“…The therapy based on agonists of LH-RH avoids the cardiovascular and mammotropic side effects of estrogens and the psychological impact of orchiectomy (22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36). It has been suggested that treatment with [D-Trp6]LH-RH produces a higher rate of response than transcapsular orchiectomy (35). The use of LH-RH agonists may be the method of choice for the treatment ofprostate cancer (3,(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36) been used successfully for the treatment of women with endometriosis (37) and children with precocious puberty (38).…”

“…It has been suggested that treatment with [D-Trp6]LH-RH produces a higher rate of response than transcapsular orchiectomy (35). The use of LH-RH agonists may be the method of choice for the treatment ofprostate cancer (3,(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36) been used successfully for the treatment of women with endometriosis (37) and children with precocious puberty (38). However, the duration of response and the median survival time in patients with prostate cancer cannot yet be estimated.…”

“…The aim of combining hormonal therapy with chemotherapy is to prevent the proliferation of both hormone-dependent and hormone-independent cells. The use of both approaches, endocrine and chemotherapeutic, may increase the rate of response and its duration (5)(6)(7)(8)(9)(10)(11)35).…”

“…The fibroblastic proliferation observed in the histological study may indicate a favorable response to the therapy. Consequently, our present view is that combined therapy should be initiated, with chemotherapy being given several hours after the first administration of LH-RH agonists (35).…”