Tolerability of Nonsteroidal Antiandrogens in the Treatment of Advanced Prostate Cancer

Abstract

This review compares the tolerability profiles of the three currently available nonsteroidal antiandrogens, flutamide, bicalutamide and nilutamide. Pharmacological effects associated with blockade of the androgen receptor are frequent with all three drugs. Gynecomastia and breast pain are seen more frequently during antiandrogen monotherapy than during combination with medical or surgical castration or castration alone, and the reverse is true for hot flashes, which are a side effect of castration. Gastrointestinal symptoms are also common to all three drugs, but diarrhea occurs more frequently in flutamide studies than in bicalutamide or nilutamide studies. Hepatotoxicity has been seen with all three antiandrogens, but acute, reversible hepatitis and fatal fulminant hepatitis have also been reported with both nilutamide and flutamide. All three drugs have been associated with asymptomatic elevations in aminotransferases and may reduce hemoglobin levels. Adverse events that have been reported with nilutamide include interstitial pneumonitis, delayed adaptation to darkness after exposure to bright light and alcohol intolerance. To date, bicalutamide appears to have some advantage over flutamide and nilutamide in terms of tolerability.

The role of antiandrogen monotherapy in the treatment of prostate cancer

“…The most common side‐effects of nonsteroidal antiandrogen monotherapy are gynaecomastia and male breast pain, and these events occur more frequently than with castration alone [29,31]. Gynaecomastia is an expected pharmacological effect of nonsteroidal antiandrogen monotherapy and is caused by an imbalance in the normal ratio of androgenic and oestrogenic activity [32].…”

“…There are differences between the nonsteroidal antiandrogens in other than pharmacological side‐effects. With flutamide monotherapy, diarrhoea occurs in up to 20% of patients and may lead to treatment withdrawal [31]. In contrast, in the EPC studies, the incidence of diarrhoea with bicalutamide was comparable with placebo (6.3% vs 6.4%, respectively) [28].…”

“…In contrast, in the EPC studies, the incidence of diarrhoea with bicalutamide was comparable with placebo (6.3% vs 6.4%, respectively) [28]. Hepatotoxicity, occasionally fatal, has also been noted with flutamide therapy [31], whereas in the EPC studies abnormal liver function occurred infrequently (3.4% for bicalutamide vs 1.9% for placebo) and changes were rarely severe [28]. Likewise, no cases of significant hepatotoxicity were noted during the studies comparing bicalutamide monotherapy and castration [10].…”

“…Likewise, no cases of significant hepatotoxicity were noted during the studies comparing bicalutamide monotherapy and castration [10]. When given as a component of MAB, nilutamide is associated with a high incidence of visual disturbances (delayed adaptation to darkness) and alcohol intolerance [15], effects not associated with either flutamide or bicalutamide [31]. Interstitial pneumonitis and hepatic dysfunction have also been reported [15,31].…”

Long‐term outcome of antiandrogen monotherapy in advanced prostate carcinoma: 12‐year results of a phase II study

“…They offer the possibility of preventing the side‐effects related to testosterone suppression, as plasma testosterone levels are unaffected or slightly elevated in man. To date, there are no comparative studies of monotherapy among the different nonsteroidal antiandrogens and there is no definitive proof, from monotherapy or combination studies, that one antiandrogen is better than another in terms of response or time to progression and survival, although some differences in tolerability have been detected [5]. The efficacy and tolerability of hormonal monotherapy with pure antiandrogens, mainly bicalutamide, as adjuvant treatment in high‐risk patients after radical prostatectomy or radiotherapy have recently been emphasized [5,6].…”