According to a new, systematic review of data from four independently conducted clinical trials, tamoxifen may be the most effective agent for the management of breast events induced by treatment with non-steroidal antiandrogens (e.g., bicalutamide) in men with prostate cancer.
This review by Kunath et al. in BMC Medicine is currently available in abstract form or as a provisional PDF of the typescript. Brief commentary on the paper is also available on the HealthDay web site.
Data on the potential of the anti-estrogenic agent tamoxifen (a drug widely used in the management of breast cancer) in the prevention and management of gynecomastia and breast pain associated with the use of non-steroidal antiandrogens like bicalutamide (Casodex) and flutamide (Eulexin) has been evolving over the past few years. Historically, it was recommended that men being treated with long-term use of non-steroidal antiandrogens receive prophylactic low-dose radiation therapy to the chest to prevent such problems.
It does need to be noted, up front, that the long-term use of anti-estrogens in men with prostate cancer may be problematic, and that further research will be needed if long-term use of tamoxifen to prevent or manage gynecomastia and breast pain is to become standard practice in men with prostate cancer on long-term antiandrogen therapy.
Kunath et al. report that they were able to identify four, relatively small, randomized, multi-center trials in which tamoxifen was compared to other forms of therapy:
- A three-arm trial, in which tamoxifen at 20 mg/day (in 37 men) was compared to the aromatase inhibitor anastrozole at 1 mg/day (in 36 men) or a placebo (in 40 men)
- A six-arm trial, in which tamoxifen at 20 mg/day (in 35 men) was compared to a placebo (in 60 men)
- A three-arm trial, in which tamoxifen at 10 mg/day (in 50 men) was compared to radiotherapy (in 50 men) or no additional treatment (in 51 men)
- A three-arm trial, in which tamoxifen at 20 ng/day (in 35 men) was compared to anastrozole at 1 mg/day (in 36 men) or a placebo (in 36 men)
The reviewers report that:
- Tamoxifen reduced the risk of gynecomastia (relative risk [RR] = 0.10) and breast pain (RR = 0.06) at 6 months compared to untreated controls.
- Tamoxifen reduced the risk of gynecomastia (RR = 0.22) and breast pain (RR = 0.25) when compared to anastrozole after a median of 12 months.
- In one study, tamoxifen reduced the risk of of gynecomastia (RR = 0.24) and breast pain (RR = 0.20) at 6 months compared with radiotherapy.
- Radiotherapy increased the risk of suffering from nipple erythema (redness of the skin due to congestion of the capillaries) and skin irritation.
- There were no significant differences between types of therapy (including placebo or non-therapy) for any other adverse events.
The authors conclude that:
- The optimal dose of tamoxifen for prevention/management of risk for gynecomastia and breast pain still needs to be determined.
- Larger, well-designed, randomized trials, with longer follow-up, are still appropriate.
- The impact of tamoxifen therapy on long-term adverse events, prostate cancer progression, and patient survival remains unclear.
However, it also appears that tamoxifen has significant potential benefits in the prevention of gynecomastia and breast pain as compared to other forms of therapy — if such long-term use does not present safety problems.