Randomised, placebo‐controlled, crossover trial of sildenafil citrate in the treatment of erectile dysfunction following external beam radiation treatment of prostate cancer

Abstract

Erectile dysfunction (ED) commonly affects the quality of life of men after treatment of prostate cancer. We conducted a placebo-controlled, crossover randomised trial to assess the efficacy and tolerability of sildenafil citrate in the treatment of ED developing after external beam radiation treatment (EBRT) of localized prostate cancer. Sixty-six patients who had developed ED following radiation treatment agreed to participate and were allocated to sildenafil or placebo to be taken prior to four sexual attempts. In the crossover period, subjects received the alternative tablet for a further four attempts. Allocation was centrally randomized, and researchers and patients were both blinded to the trial arm. Efficacy was assessed using the International Index of Erectile Function (IIEF) questionnaire and with a separate global efficacy question. Forty-three subjects completed the study. There was a significant increase in mean scores from baseline for all domains of the IIEF with sildenafil compared with placebo (P < 0.001). Affirmative response to the global efficacy question was more common after taking sildenafil compared with placebo. In approximately half of the patients, the improvement in the erectile function domain score corresponded to a moderate improvement in ED (e.g. success 'sometimes' to 'most times'). Sildenafil was associated with mild flushing, nasal stuffiness or indigestion in 8-10% patients and moderate flushing in 10%. The current study adds to the evidence that phosphodiesterase inhibitors are an effective and well-tolerated treatment for ED after EBRT for prostate cancer.

Phosphodiesterase-5 Inhibitors Could Be Efficacious in the Treatment of Erectile Dysfunction after Radiotherapy for Prostate Cancer: A Systematic Review and Meta-Analysis

“…Although two severe headaches [7] and one case of severe dyspepsia [3] occurred in the PDE5i group, almost all side effects were mild to moderate and transient, and no cerebrovascular accident or coronary event was observed. Meanwhile, only one drug was discontinued because of side effects, as reported by Harrington et al [3] in 2010. Furthermore, the severity of side effects did not differ between the PDE5i group and the placebo group (RR 4.00, 95% CI 0.45-35.30, p = 0.21).…”

“…Finally, four publications (RCTs) were identified and included in the review [3,7,11,12]. The characteristics and quality of the included studies are presented in table 3.…”

“…The characteristics and quality of the included studies are presented in table 3. A total of four RCTs had evaluated oral PDE5i for treating ED after PCa radiotherapy [3,7,11,12], including three RCTs of sildenafil vs. placebo [3,7,12] and one RCT of tadalafil vs. placebo [11], with no related RCT of vardenafil vs. placebo. One RCT evaluated the effect of sildenafil on erectile function after both radiotherapy and short-term androgen deprivation therapy [7].…”

“…Information on efficacy was primarily based on three RCTs [7,11,12], and the data on SE were collected and synthesized from all four articles [3,7,11,12]. The reason why the study by Harrington et al [3] was not included in the analysis of efficacy was that they did not report values of standard deviation and presented their results as IIEF subscores (not individual items), therefore making it unsuitable for statistical calculations.…”

“…Because of improved PCa screening, more patients have been diagnosed at a younger age and at an earlier stage, which has translated to an increased number of localized diseases receiving external beam radiotherapy with a curative intent [2]. However, erectile dysfunction (ED) is a relatively common complication after radiotherapy for PCa [3]. Although advanced radiation techniques, such as three-dimensional conformal external beam radiotherapy, were assumed to cause less ED, the current literature rates of ED after radiotherapy still vary from 6 to 84% [4].…”