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Tamoxifen 20 mg/day Effective for Managing Gynaecomastia and Breast Pain From Bicalutamide: Presented at EAU

By Chris Berrie

BERLIN, GERMANY -- March 23, 2007 -- Tamoxifen, at a dose of 20 mg/day, is highly effective for managing gynaecomastia and breast pain associated with bicalutamide (Casodex) for patients with localised or locally advanced prostate cancer, and its coadministration with bicalutamide does not appear to affect cancer control.

Bicalutamide is the most widely studied nonsteroidal antiandrogen (NSAA) as monotherapy for patients with prostate cancer. However, a common adverse effect of all agents in this drug class is gynaecomastia and breast pain.

In their multicentre, double-blind, randomised, placebo-controlled, dose-response trial presented here at the 22^nd Annual Congress of the European Association of Urology (EAU), researchers examined the effect of prophylactic tamoxifen use on the incidence of gynaecomastia and breast pain and cancer control in patients receiving bicalutamide monotherapy.

In a presentation here on March 21^st, investigator Yves Fradet, MD, principal investigator and professor of urology and surgery, Centre De Recherche, CHUQ-Hôtel-Dieu, Québec, Canada, said the primary endpoints were incidence and degree of these breast events and prostate-specific antigen (PSA) inhibition.

The researchers enrolled 282 men with mean age of 74 years to receive bicalutamide 150 mg/day plus either placebo (n = 60) or daily tamoxifen at 1 mg (n = 58), 2.5 mg (n = 47), 5 mg (n = 48), 10 mg (n = 34), or 20 mg (n = 35). Tamoxifen was administered for 12 months, with a further 12 months of bicalutamide 150 mg/day alone.

At baseline, there were no significant differences in tumour stage proportions (all patients: T1, 29.4%; T2, 40.2%; T3-T4, 30.5%) and primary therapies received (all patients: radical prostatectomy, 5.5%; radiotherapy, 12.8%; watchful waiting/newly diagnosed, 82.5%) across all treatment groups. Median PSA levels were also similar across treatment groups.

At both 6 and 12 months, the breast events of gynaecomastia and/or breast pain were significantly reduced (P < .05) for tamoxifen doses of 2.5 mg/day or greater, with the optimal dose of 20 mg/day providing more than 80% reduction.

"However," Dr. Fradet noted, "when tamoxifen was removed from the treatment regimen from 12 months, at 24 months median follow-up the patients were back to greater than 90% breast events, as in the placebo group."

For bicalutamide-induced PSA inhibition, prophylactic tamoxifen had no adverse effects, with an 85% to 95% median decrease from baseline for PSA maintained across all groups through the full 24 months.

For the monitored hormone levels, as median percentage changes from baseline, the bicalutamide-induced increases for total testosterone, free testosterone, and steroid-hormone-binding globulin showed no changes across all groups. However, those for luteinising hormone showed an increase (control, 117%; tamoxifen all doses, 173-295%), as they did for follicle-stimulating hormone (less than or equal to 40% increase over unchanged control), although these changes were not specifically tamoxifen-dose related.

Dr. Fradet indicated that addition of tamoxifen to bicalutamide treatment generally did not increase the incidence of adverse events. However, there was up to a 4-fold increase in the percentage of patients with hot flushes at higher tamoxifen doses.

Prophylactic tamoxifen is highly effective in management of gynaecomastia and breast pain in these bicalutamide-treated patients with localised or locally advanced prostate cancer, with an optimal dose of 20 mg/day, he concluded.

He stressed, "Coadministration of tamoxifen and bicalutamide does not appear to affect cancer control, as far as can be measured by bicalutamide-induced PSA response."

The return of the breast events in these bicalutamide-treated patients following withdrawal of tamoxifen indicates the need for its coadministration throughout bicalutamide treatment for maintenance of its prophylactic effects, he noted.

The study was supported by AstraZeneca.


[Presentation title: Tamoxifen as Prophylaxis for Prevention of Gynaecomastia and Breast Pain Associated With Bicalutamide 150 Mg Monotherapy in Patients With Prostate Cancer. Abstract 24]

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