西地那非可保护前列腺癌放疗患者性功能

波士顿——美国放射肿瘤学会(ASTRO)年会上报告的一项研究显示，曾使无数老年男性重振雄风的西地那非(伟哥)，也有助于保护前列腺癌放疗患者的性功能。

纪念斯隆凯特林癌症中心放射肿瘤医生Michael J. Zelefsky博士报告称，随机双盲试验结果表明，前列腺癌患者在放疗前、中、后6个月服用枸橼酸西地那非，无论是在性功能还是自我报告总满意度方面，均优于服用安慰剂的患者，但同时接受雄激素剥夺治疗的患者似乎不能从中受益。


Michael J. Zelefsky 博士

Zelefsky博士指出，动物实验已经表明，西地那非、伐地那非(艾力达)以及他达那非(西力士)等磷酸二酯酶-5(PDE5)抑制剂可通过保护阴茎海绵体和参与勃起的平滑肌血管内皮功能，维持或恢复阴茎功能。欧洲一项随机试验也显示，与安慰剂相比，伐地那非可改善双侧神经保留前列腺切除患者的自主勃起功能(Eur. Urol. 2008;54:924-31)。而此次研究从根本上证明了前列腺癌放疗患者阴茎功能康复的重要性，也表明患者在改善性功能结局方面受益明显，因而意义重大。

预处理效果评估

该研究入组295例性功能良好[定义为勃起功能国际指数5(IIEF-5)评分≥17]的择期接受外照射治疗(EBRT)或近距离治疗的前列腺癌患者，并按照2:1的比例随机服用西地那非(50 mg/d)或安慰剂，从放疗前3天开始服药并持续6个月。随访期间患者自行评估IIEF-5(包括勃起功能、高潮功能、性交满意度和总满意度)、国际前列腺症状评分(IPSS)并回答生活质量问卷，第1年每3个月1次，第2年每6个月1次。

对31例接受雄激素剥夺治疗患者勃起功能评分考察结果显示，西地那非组与安慰剂组相比未见明显差异或改善，表明这类患者无明显受益。因此，该项分析排除了这类患者，重点关注142例未接受接受雄激素剥夺治疗的患者。

基线时，两组患者吸烟史、糖尿病或高血压等有可能影响勃起功能的因素均未见差异。结果显示，总体上，西地那非组总IEFF-5评分在治疗后6个月(P=0.006)、12个月(P=0.02)和24个月(P=0.04)均明显高于安慰剂组，但24个月时仅在性欲(P=0.001)和总满意度(P=0.04)方面表现出明显优势。此外，12个月后上述组间差异的显著性有所下降。

能否成为新标准？

特邀评论者、梅奥医院放射肿瘤学教授Thomas M. Pisansky博士认为，虽然该研究存在一定局限性，包括治疗方案不同、每日1次给药而非多次给药以及缺乏性伴侣信息，但这并不影响研究结论。该研究的确为早期使用PDE5抑制剂提供了新证据，也代表了目前的一种新标准，但需要进一步研究加以确认，而这方面的工作已经开始。

Pisansky博士还强调，放射肿瘤医生应采用IIEF-5等经过验证的性功能评价方法评估前列腺癌患者放疗效果。

Zelefsky博士和另一共同作者报告接受伟哥生产商辉瑞制药的资助，Pisansky博士报告无利益冲突。

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By: NEIL OSTERWEIL, Internal Medicine News Digital Network

BOSTON – The drugs that have revitalized the love lives of millions of aging men may also help preserve sexual function in men undergoing radiation therapy for prostate cancer, investigators reported at the annual meeting of the American Society for Radiation Oncology.

Men who took sildenafil citrate (Viagra) before, during, and for 6 months after radiotherapy for prostate cancer had better sexual function and reported better overall satisfaction than did men who took placebo in a randomized double-blind trial, said Dr. Michael J. Zelefsky, a radiation oncologist at Memorial Sloan-Kettering Cancer Center in New York City.

Men who were also treated with androgen deprivation, however, did not appear to experience a benefit from sildenafil and were excluded from the analysis.

"We believe our study is a very important one, for it demonstrates proof of principle that penile rehabilitation is important in the population of radiotherapy patients treated for prostate cancer, and demonstrates a significant benefit for improved sexual function outcomes," Dr. Zelefsky said at a plenary session.

Studies in animal models have suggested that phosphodiesterase-5 (PDE5) inhibitors such as sildenafil, vardenafil (Levitra), and tadalafil (Cialis) could help to preserve or rehabilitate penile function by protecting the vascular endothelium of the corpus cavernosum of the penis and smooth muscle tissue involved in erections.

Dr. Zelefsky pointed to a European randomized trial showing that patients who had undergone bilateral nerve-sparing prostatectomy and were randomized to vardenafil had improved spontaneous erections compared with placebo-taking controls (Eur. Urol. 2008;54:924-31).

Pretreatment Potency Assessed

The current study enrolled 295 men who had excellent sexual function (defined as a score of 17 or greater on the International Index of Erectile Function 5 [IIEF-5]) and were scheduled to undergo radiotherapy to the prostate with either external-beam radiation (EBRT) or brachytherapy. They were randomly assigned on a 2:1 basis to sildenafil or placebo, respectively.

Sildenafil was given in a 50-mg dose starting 3 days before therapy and continuing out to 6 months. Patients were followed with the patient-derived IIEF-5 (including domains of erectile function, orgasmic function, intercourse satisfaction, and overall satisfaction), International Prostate Symptom Score (IPSS), and a quality of life questionnaire every 3 months for the first year, and then every 6 months up to 2 years.

"Thirty one patients were treated with androgen-deprivation therapy, and when we looked at erectile function scores over time, there were no significant differences or improvements noted with the use of daily sildenafil compared to the placebo group, suggesting that there was no apparent benefit among this cohort of patients. For this reason, we excluded this cohort and turned our attention to a group of patients who did not receive androgen deprivation therapy, leaving us with an evaluable cohort of 142 patients," Dr. Zelefsky said. The analysis included patients who completed surveys before treatment and at least one additional time period.

There were no significant between-group differences at baseline in factors that might affect erectile function, such as smoking history, diabetes, or hypertension.

Overall total IEFF-5 scores were significantly higher among patients in the sildenafil arm at 6 (P = .006), 12 (P=.02) and 24 months (P = .04) after therapy. However, at 24 months, there were significant differences in favor of sildenafil only in the IEFF-5 domains of sexual desire (P = .001) and overall satisfaction (P = .04).

The investigators also noted that the differences between the treatment groups became less apparent beyond 12 months.

Does This Set a New Standard?

The study had a few minor limitations, including variations in treatment, once-daily rather than more frequent dosing, and the lack of information on a relationship or partner effect, but these do not detract from the conclusion, said invited discussant Dr. Thomas M. Pisansky, professor of radiation oncology at Mayo Clinic, Rochester, Minn.

"Nonetheless, this does serve as an additional test of proof of principle of early PDE5 inhibitor use. Does this represent a new standard? I believe that for the time being it certainly does, but additional study is warranted, and that is ongoing," he said.

Dr. Pisansky added that it is incumbent upon radiation oncologists, when evaluating patients for radiotherapy to the prostate, to incorporate a validated instrument of sexual function such as the IIEF-5.

Dr. Zelefsky and a coauthor disclosed receiving grants from Pfizer, maker of Viagra. Dr. Pisansky reported no conflicts of interest.