Effect of a new leuprorelin formulation on testosterone levels in patients with advanced prostate cancer

Leuprorelin is a well known luteinising hormone releasing hormone (LHRH) agonist. The drug is effective in the treatment of advanced prostate cancer and is well tolerated. This article reviews published literature (based on a search of PubMed, EMBASE and Biosis databases to the end of 2005) and other sources of data on a new formulation of leuprorelin acetate (Eligard) for use in the treatment of hormone-dependent advanced prostate cancer. This product takes advantage of a novel delivery system (Atrigel) which forms an implant in situ that is capable of delivering double doses of leuprorelin consistently to provide better, more sustained testosterone suppression compared with a microsphere leuprolide acetate formulation. Two formulations, 7.5 mg and 22.5 mg, are currently available with duration of action of 1 and 3 months, respectively. The 2-week stability at room temperature prior to mixing facilitates its use and reduces the potential for waste.

In clinical studies of the new leuprorelin acetate formulation reviewed here, all patients achieved testosterone levels < or = 50 ng/dL and up to 98% of patients showed levels comparable to those resulting from surgical bilateral orchidectomy (< or = 20 ng/dL). Both formulations showed minimal breakthroughs, defined as a rise in testosterone levels after reaching levels of 50 ng/dL. The safety profile is typical of LHRH agonists, with mild to moderately severe 'hot flushes' being the most common adverse event. The higher dose of 22.5 mg, with a volume of 0.375 mL is administered subcutaneously via a small 20G needle, causing little local discomfort.

Prostate cancer remains a major cause of morbidity and mortality in older men. In the majority of cases, suppression of serum testosterone levels is very effective. The level of testosterone suppression is currently under debate, with ideal suppression levels ranging from 20 to 50 ng/dL. Not all LHRH agonist therapy achieves the same degree of testosterone suppression as bilateral orchidectomy. The new leuprorelin acetate (Eligard) appears to achieve a testosterone suppression of 20 ng/dL in 98% of patients, while maintaining a side effect profile comparable to other products in its class.