ST LOUIS (MD Consult) - On March 31, 2010, the US Food and Drug Administration (FDA) issued a notice that it is evaluating clinical trial data that may suggest that men taking Stalevo, a medication indicated for Parkinson's disease, may be at increased risk for prostate cancer. At this time, the FDA's review of Stalevo is ongoing, and no new conclusions or recommendations about the use of this drug have been made.

In the clinical trial under investigation (Stalevo Reduction in Dyskinesia Evaluation–Parkinson's Disease [STRIDE-PD]), patients receiving Stalevo were compared with patients receiving Sinemet. The time to onset of dyskinesia was the key concept being evaluated during the trial. Stalevo contains a combination of the active ingredients entacapone, carbidopa, and levodopa, and Sinemet contains a combination of carbidopa and levodopa.

The STRIDE-PD study was a multicenter, international, double-blind, randomized, parallel-group, controlled trial conducted between September 2004 and November 2008. A total of 745 patients with Parkinson's disease were enrolled in the trial and 541 completed treatment. Of the patients who completed treatment, 265 patients received Stalevo and 276 received carbidopa/levodopa. Treatment duration ranged from 2.6 years to 4 years (mean duration, 2.7 years). The average age of patients in the trial was approximately 60 years. The majority of subjects were white (95.2%) and male (62.7%).

A total of 467 men received treatment in the trial. A higher number of cases of prostate cancer occurred in patients in the Stalevo-treated group compared with patients in the carbidopa/levodopa group. Specifically, 9 of 245 men (3.7%; 95% confidence interval [CI], 1.69%-6.86%) were diagnosed with prostate cancer in the Stalevo group compared with 2 (0.9%) of 222 men in the carbidopa/levodopa group. The incidence rate of prostate cancer was 14 cases/1,000 patient years for Stalevo and 3.2 cases/1,000 patient years for carbidopa/levodopa. The odds ratio for the occurrence of prostate cancer in men receiving Stalevo was 4.19 (95% CI, 0.90-19.63). The duration of therapy before prostate cancer was diagnosed in patients in the Stalevo-treated group ranged from 148 to 949 days (mean, 664 days).

STRIDE-PD is the first long-term clinical trial evaluating the use of Stalevo in patients with Parkinson's disease. Previous clinical trials involving treatment with Stalevo for Parkinson's disease demonstrated no increased risk for prostate cancer. However, most of these trials were conducted for less than 1 year, whereas STRIDE-PD was conducted over a 4-year period.

The FDA is exploring additional ways to better understand whether Stalevo actually increases the risk of prostate cancer. Health care professionals should keep in mind that prostate cancer is most commonly diagnosed in men who are of the same age as the men included in the STRIDE-PD trial, and they should be aware that a possible risk exists in men maintained on Stalevo therapy. Current guidelines for prostate cancer screening should be followed.

 

圣路易斯(MD Consult)——2010年3月31日，美国食品药品管理局(FDA)发布了一则通告，内容为FDA正对临床试验数据进行评估，这些数据可能表明，服用Stalevo(一种适用于治疗帕金森病的药物)的男性患者可能有较高的前列腺癌发病风险。目前，FDA对Stalevo的审查还在进行之中，尚未得出新的有关该药使用的结论或建议。

在接受调查的临床试验[Stalevo减少运动障碍效果评估——帕金森病(STRIDE-PD)]中，研究者将接受Stalevo治疗的患者与接受息宁(Sinemet)治疗者进行比较。试验过程中的关键评价指标为运动障碍的发病时间。Stalevo为活性成分恩托卡朋、卡比多巴及左旋多巴构成的复方制剂，息宁为卡比多巴与左旋多巴的复方制剂。

STRIDE-PD研究是一项在2004~2008年间开展的多中心、国际性、双盲、随机、平行对照试验。该试验共纳入745例帕金森病患者，541例完成治疗。在完成治疗的患者中，有265例接受Stalevo治疗，而276例接受卡比多巴/左旋多巴联合治疗，历时2.6~4年(平均持续时间，2.7年)。试验的受试者平均年龄约60岁。白种人(95.2%)和男性(62.7%)在受试者中占大多数。

 

试验中共有467例男性接受治疗。与卡比多巴/左旋多巴治疗组相比，Stalevo治疗组患者前列腺癌的发病率较高。详言之，Stalevo治疗组245例男性中有9例[3.7%；95%可信区间(CI)，1.69%~6.86%]被诊断为前列腺癌，而卡比多巴/左旋多巴治疗组的222例男性患者中仅有2例(0.9%)。接受Stalevo治疗者的前列腺癌发病率为14例/1,000个患者年，而接受卡比多巴/左旋多巴治疗为3.2例/1,000个患者年。接受Stalevo治疗的男性前列腺癌发生率比值比为4.19(95% CI，0.90~19.63)。Stalevo治疗组患者在诊断为前列腺癌之前的治疗持续时间为148~949天(平均664天)。                

STRIDE-PD是首项评价帕金森病患者应用Stalevo治疗的长期临床试验。先前与帕金森病患者应用Stalevo治疗有关的临床试验证实前列腺癌风险无增加。然而，其中大多数试验历时不足1年，而STRIDE-PD试验历时4年。

FDA目前在寻求其他方法，以便更好地了解Stalevo是否确实会增加前列腺癌风险。医护人员应谨记，前列腺癌诊断更常见于与STRIDE-PD试验纳入的男受试者同龄的男性，而且他们应知道，接受Stalevo持续治疗的男性存在疑似风险。当前的前列腺癌筛查指南应予以遵从。