Health and Prostate

Overview.

Until recently, estramustine (Pfizer’s Emcyt / Estracyt, Nihon Kayaku’s Estracyt, generics) was one of two chemotherapeutic agents marketed for the treatment of CaP. Estramustine was specifically designed to combine antiandrogen activity with cytotoxicity. Its poor clinical performance as a single agent prompted researchers to assess estramustine in combination with other cytotoxics. One such study is discussed in the upcoming section “Doc-etaxel / Estramustine.

Mechanism Of Action.

Estramustine‘s exact mechanism of action is unknown. Researchers postulate that it has a dual mechanism of action. Prior to metabolism, the intact molecule has an antimitotic action, possibly achieved by the stabilization of microtubule dynamics by binding to a novel site in tubulin. Additionally, some of the metabolites exert an antigonadotrophic effect owing to their estrogen-like activity. This antigonadotrophic effect suppresses testosterone.

Clinical Performance.

In a randomized, Phase III trial conducted by the Uro-logical Group of the European Organization for Research and Treatment of Cancer, 227 patients with T3 or T4 CaP were randomized to estramustine or diethylstilbestrol therapy. The patients in the estramustine arm received a dose of 280 mg twice a day for the first eight weeks, after which the dose was reduced to 140 mg twice a day. Patients randomized to the diethylstilbestrol arm were treated with 1 mg three times each day. Duration of response was made by assessment by palpation of local tumor response. Patients treated with diethylstilbestrol had a significantly better local tumor response, but the investigators found no significant difference between the two drug treatments in response rate of metastases, interval to local and distant progression, and overall survival. Diethylstilbestrol was significantly more cardiotoxic than estramustine, while estramustine caused gastrointestinal toxicity in 25 patients, six of whom stopped treatment.