Introduction
Materials and methods
Results
Characteristics of included studies
Radiation therapy
Publication/author | Patients (N) | Trial design | Study period | Interventions and results | Side effects and/or QoL |
---|---|---|---|---|---|
Tyrell et al. [6] | 106 | Randomized, sham controlled, double blind | 11/1999–06/2001 | Prophylactic single dose electron beam RT with 10 Gy vs. sham RT. RT reduced gynecomastia 52% vs. 85%; OR, 0.13; 95% CI, 0.04–0.38; p < 0.001. Breast pain was similar in both arms (83% vs. 91%; OR, 0.25; 95% CI, 0.05–1.27; p = 0.221) but severity of pain tended to improve after RT (p = 0.043) | RT-related adverse events were experienced by 17 of 52 patients (33%) who received RT (breast/nipple erythema, breast/nipple tenderness, or skin irritation) |
Ozen et al. [7] | 125 | Randomized | 06/2003–10/2005 | Prophylactic RT using 2 × 6 Gy electron beam vs. no RT RT reduced gynecomastia 15.8% vs. 50.8% while the rate of breast pain was similar being 36.4% vs. 49.2% | Adverse events were mild and observed in 6 or 8 patients per treatment arm |
Drug therapy
Publication/author | Patients (N) | Trial design | Study period | Interventions and results | Side effects and/or QoL |
---|---|---|---|---|---|
Fradet et al. [8] | 282 | Randomized, placebo controlled | 11/2002–06/2003 | Patients were randomized to different prophylactic doses of TMX (1, 2.5, 5, 10, or 20 mg/day) or placebo given for 12 months. Increasing doses of TMX decreased incidence of breast events (gynecomastia and/or breast pain) in a dose-dependent manner at the 3‑, 6‑ and 12-month assessments, where breast events were presented in 96.7% or 98.3% after placebo and in 8.8% or 20.6% of patients after 20 mg TMX. At 24 months (i.e., after 12 months of bicalutamide monotherapy), a high incidence of breast events (>90%) was seen in all groups | Dizziness and hot flushes increased by TMX |
Bedognetti et al. [9] | 80 | Randomized, noninferiority | 12/2003–2/2006 | Patients were randomized to prophylactic daily TMX 20 mg or daily TMX 20 mg for 8 weeks and weekly TMX 20 mg thereafter. After a preplanned interims analysis gynecomastia developed in 31.7% of patients in the daily group and in 74.4% of patients in the weekly group (p < 0.0001), and it was more severe in patients who switched to weekly tamoxifen (p = 0.001). Mastalgia occurred in 12.2 and 46.1% of patients, respectively (p = 0.001) | No difference in treatment-related toxicity |
Saltzstein [10] | 107 | Randomized, placebo controlled | n.a. | Patients were randomized to 3 months of prophylactic daily TMX 20 mg or daily anastrozole 1 mg or placebo. After 3 months bicalutamide was continued for another 9 months. Patients who developed gynecomastia and/or breast pain during this period underwent TMX or anastrozole for 3 months. The incidence of gynecomastia and/or breast pain was 11.8% for TMX, 63.9% for anastrozole and 69.4% for placebo (p < 0.0001). Resolution of gynecomastia and breast pain for therapeutically treated patients occurred in 65.4% in the TMX group, 71.8% of patients in the placebo group (who received TMX) and 18.8% of patients in the anastrozole group | Dizziness increased by TMX |
Boccardo [11] | 114 | Randomized, placebo controlled | 12/2000–12/2002 | Patients were randomized to 48 weeks of prophylactic daily TMX 20 mg or daily anastrozole 1 mg or placebo. Gynecomastia developed in 73% of patients in the bicalutamide group, 10% of patients in the bicalutamide-TMX group, and 51% of patients in the bicalutamide-anastrozole group (p = 0.001); breast pain developed in 39%, 6% and 27% of patients, respectively (p = 0.006) | Treatment was well tolerated and the incidence of toxicity was higher in the anastrozole arm (69.5% of patients) as compared to placebo (37.5%) or TMX (35.1%) |
Serretta [12] | 176 | Randomized controlled | 06/2005–06/2007 | Patients were randomized to 1 year daily 20 mg TMX within 1 month from the onset of gynecomastia and/or breast pain (Arm A, therapeutic treatment) or 1 year prophylactic daily 10 mg TMX (Arm B). In Arm A gynecomastia and/or breast pain increased with time with a rate of 39.8%, 57.8%, 69.9% and 78.3% at 3, 6, 9, and 12 months after initiation of bicalutamide. After therapy with TMX gynecomastia and/or breast pain persisted in 27.7% of cases. In arm B, the prevalence of gynecomastia and/or breast pain was 35% after 12 months of therapy. The difference in gynecomastia and/or breast pain between the 2 arms was statistically significant (p = 0.0001). The differences in prevalence of gynecomastia and breast pain between the 2 arms both favored TMX prophylaxis (p = 0.0001 and p = 0.001, respectively) | No significant difference between the trial arms |
Radiation therapy vs. drug therapy
Publication/author | Patients (N) | Trial design | Study period | Interventions and results | Side effects and/or QoL |
---|---|---|---|---|---|
Di Lorenzo et al. [13] | 102 | Randomized controlled | 01/2002–02/2004 | Patients were randomized no additional treatment (control arm) or prophylactic daily 10 mg TMX over 24 weeks or prophylactic low dose RT using 1 × 12 Gy. Patients from the control arm who developed gynecomastia and/or breast pain were subsequently randomized to TMX or RT. Of the control group 67% of patients developed gynecomastia compared with 8% after prophylactic TMX and 34% after prophylactic RT. Breast pain was more frequent in the control group than after TMX or RT (58% vs 7% and 30%, respectively). Differences were significant (p = 0.001 or p = 0.01). In patients of the control group who had gynecomastia and/or breast pain a significant decrease in symptoms was achieved in those receiving TMX (p = 0.05) For further information compare below (Perdonà et al.) | There were no significant differences between the groups with respect to toxicity |
Perdonà et al. [14] | 151 | Randomized controlled | 01/2002–02/2004 | Same trial as Di Lorenzo et al., published with a larger number of patients but basically the same results | There were no significant differences between the groups with respect to toxicity |