The 20-milligrams per day tamoxifen therapy reduced the severity of androgen deprivation therapy-related symptoms in prostate cancer patients.
Researchers at nine Italian institutions and the Group for the Study of Urologic Tumors Foundation presented results of a study showing that tamoxifen, 10 mg daily, as prophylaxis significantly reduces, but may not always prevent, gynecomastia. A stronger dose, 20 mg/d, appears to be slightly more effective at relieving symptoms when administered at the first sign of those symptoms, the research team reported at the AUA annual meeting in Orlando, FL.
"The difference is primarily a matter of the intensity of the symptoms from the bicalutamide," first author Vincenzo Serretta, MD, of the section of urology, University of Palermo, told Urology Times. "When we gave the tamoxifen as prophylaxis, there were no interruptions of treatment. However, in the 20-mg arm, about 3% of the patients, actually two patients, interrupted the treatment due to intolerance. That is not a big difference, but it is a difference."
Both groups were followed with routine laboratory examinations and with testosterone and PSA analyses at the start of treatment and at 3-month intervals for up to 1 year. Gynecomastia and pain were self-evaluated, using a visual analog scale, and gynecomastia also was evaluated by physical examination. Of the 176 men, 83 patients in arm A and 60 patients in arm B were followed for between 8 and 33 months, and were available for evaluation at the time the study was prepared for presentation at the AUA meeting.
In the 20-mg arm, the incidence of gynecomastia and breast pain increased from 33% at 3 months to 61% at 12 months; however, the 20-mg/d tamoxifen therapy produced a reduction in the severity of symptoms, particularly pain, in all patients. At 12 months, 23% of the cohort continued to present with gynecomastia and 18% with pain. Two of the patients in this arm withdrew from treatment as a result of dizziness and four patients withdrew saying that they did not find their gynecomastia troublesome enough to merit intervention.
Significant symptom relief
The 10-mg prophylaxis therapy significantly reduced the incidence of symptoms (p<.0001), but did not abolish them. At 3 months, gynecomastia and breast pain were reported in 17.2% and 17.9% of patients, respectively. At 12 months, these symptoms were reported in 31.1% and 33.3% of patients, respectively, in the 10-mg cohort, but the severity of these symptoms appeared to be limited. No patient in this group interrupted bicalutamide treatment due to symptoms.
No difference was discerned in PSA responses between the two groups: 0.47 ng/mL in arm A and 0.90 ng/mL in arm B. In addition, no difference in plasma testosterone levels was observed: 770.2 ng/mL in arm A and 703.8 ng/mL in arm B. Five patients (6%) in arm A and three patients (5%) in arm B interrupted bicalutimide treatment due to PSA progression.
"This study has changed my practice," Dr. Serretta said. "If a patient is treated with radiotherapy and then bicalutamide, perhaps 50% of them will develop gynecomastia and pain. Now we routinely initiate prophylaxis with tamoxifen. They may still have gynecomastia, but the breasts are smaller and the pain is tolerable. Their problems are smaller."