THERAPEUTIC EFFECTS OF LEUPRORELIN MICROSPHERES IN PROSTATE-CANCER

Leuprorelin has demonstrated effectiveness comparable to orchiectomy a nd oral diethylstilboestrol for the palliation of advanced prostate ca ncer. Unlike orchiectomy, leuprorelin's effects are reversible; also l euprorelin is not associated with the cardiovascular or thromboembolic adverse effects of oestrogens. For these reasons, leuprorelin has bee n widely used as an alternative to surgical castration or to oestrogen s in the treatment of metastatic prostate cancer. Sustained-release le uprorelin microsphere formulations have been developed which exhibit z ero order release of active drug from the injection site, such that in the United States the 7.5 mg dosage strength is recommended to be adm inistered once a month and the 22.5 mg dosage strength once every thre e months. Although most patients will have suppressed release of pitui tary luteinizing hormone by the third or fourth week after the first d ose of depot leuprorelin, 4-5% of treated patients have been reported to have delayed responses, taking many more weeks or months to respond . A transient biochemical hormone escape has also been reported, altho ugh worsening of clinical symptoms has not accompanied the elevation o f serum testosterone levels during treatment. Usually, leuprorelin is initiated as monotherapy when patients with advanced prostate cancer b ecome symptomatic. However, newer studies of combination therapy of lu teinizing hormone releasing hormone analogs with antiandrogens suggest that early initiation of therapy, at the time of diagnosis of advance d disease, may be beneficial, particularly in a subgroup of patients w ith small volume disease and good performance status. Leuprorelin is a lso undergoing evaluation as neoadjuvant therapy prior to radical pros tatectomy for localized prostate cancer. Preliminary studies suggest t hat neoadjuvant leuprorelin in combination with an antiandrogen may be effective in downstaging prostate rumours. Leuprorelin commonly produ ces several adverse effects: hot flashes, decreased libido and impoten ce, and tumour flare. (C) 1997 Elsevier Science B.V.