ASCO GU前瞻：MDV3100和镭-223成为焦点

The 2012 Genitourinary Cancers Symposium, to be held Feb. 2-4, will feature potentially practice-changing data on two novel agents – MDV3100 and radium-223 chloride – in prostate cancer.

• Results of the phase III AFFIRM trial, to be reported in full Feb. 2, show that the investigational oral androgen–receptor signaling inhibitor MDV3100 prolongs overall survival in progressive castration-resistant prostate cancer after failure of docetaxel (Taxotere).

Men given this agent lived on average nearly 5 months longer than their counterparts given a placebo, according to a press preview of data by the American Society of Clinical Oncology (ASCO). There was no increase in rates of grade 3 or higher adverse events or serious adverse events with MDV3100. The rate of seizures was 0.6% with the drug and 0% with placebo.

• Results of the placebo-controlled phase III ALSYMPCA trial show that the first alpha-particle–emitting drug to target bone, radium-223 chloride (Alpharadin), prolonged overall survival by nearly 3 months (prompting early trial closure) and delayed the time to skeletal-related events by about 5 months in men with bone-only metastatic castration-resistant prostate cancer who had received or were not candidates for docetaxel.

Radium-223 chloride was well tolerated, and there were no cases of leukemia. The U.S. Food and Drug Administration has granted Fast Track status to this investigational agent.

In addition, two large observational studies using linked Surveillance, Epidemiology, and End Results (SEER) and Medicare data, will likely add to the debate regarding the most cost-effective treatment for prostate cancer, and in particular, the pros and cons of various radiation therapy options.

• Investigators at the University of North Carolina at Chapel Hill and University of North Carolina Hospitals will report findings in more than 12,000 men with localized prostate cancer, showing a lower rate of subsequent cancer treatment with intensity-modulated radiation therapy (IMRT) vs. conformal radiation therapy; bowel toxicity and hip fracture were less common with the former, whereas erectile dysfunction was less common with the latter. In addition, proton therapy did not yield a significantly lower rate of subsequent cancer treatment vs. IMRT, and also had a higher rate of bowel toxicity.

• Investigators at the Cleveland Clinic and Kaiser Permanente will report outcomes after a median follow-up of 71 months in 137,427 men with prostate cancer of various stages, showing that of three common therapies – prostatectomy, external-beam radiation therapy (EBRT), and brachytherapy – EBRT was associated with the highest cumulative incidences of gastrointestinal and genitourinary therapy–related toxicity necessitating intervention and also was the most costly.

In another study of note, also being reported in full Feb. 2, researchers will present findings regarding the impact of vigorous exercise on gene expression in the prostate gland that may help explain its benefit in reducing progression.

• This study in a low-risk prostate cancer population under active surveillance has found that a set of 184 genes in normal prostate tissue are differentially expressed between men who exercise vigorously at least 3 hours a week and men who exercise less intensively, according to results to be presented in a poster session. A number of tumor suppressor genes were upregulated in the vigorous exercisers, and pathway analysis showed that the DNA repair and cell cycle pathways were positively modulated.

For ongoing coverage of these and other presentations at the ASCO Genitourinary Cancers Symposium, visit The Oncology Report.

For earlier reports on these new prostate cancer agent, click on:

• Radium-223 Could Alter Metastatic Prostate Cancer Management

A report from the European Multidisciplinary Cancer Congress in September 2011.

• Positive Data on Alpharadin Could Accelerate Filing Timeline

A report on early halting of the radium-223 trial in June 2011

• Prostate Cancer Drug

A video interview with Dr. Howard Scher on the importance of early MDV3100 data presented at the Genitourinary Symposium in 2009.

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2012年生殖泌尿肿瘤研讨会(ASCO GU)将于2月2~4日举行，本次会上将公布2种前列腺癌新药——MDV3100和镭-223——的最新研究数据，临床实践可能因此而改变。

·2月2日将公AFFIRMⅢ期试验的结果：研究性口服雄激素受体信号抑制剂MDV3100可延长多西他赛治疗失败后去势耐药性前列腺癌患者的总生存期。根据美国临床肿瘤学会(ASCO)发布的预告，接受MDV3100治疗者的平均生存期比接受安慰剂治疗者延长了近5个月，而≥3级不良事件或严重不良事件的发生率并未增加。两组患者分别有0.6%和0的患者发生癫痫。

·Ⅲ期ALSYMPCA安慰剂对照Ⅲ期试验的结果显示：首个针对骨骼的α粒子发射药物——镭-223氯化物(Alpharadin)——可使曾接受或不适宜接受多西他赛治疗、仅有骨转移的去势耐药性前列腺癌患者的总生存期延长近3个月(促使该试验提前结束)，并使骨相关事件的发生时间延迟约5个月。

镭-223氯化物的耐受性良好，无患者发生白血病。美国食品药品管理局(FDA)已允许该药进入快速审批通道。

另外，还有2项大规模观察性研究将为围绕前列腺癌治疗成本效益比、多种放疗选择利弊的讨论提供新数据。

·北卡罗来纳大学和北卡罗来纳医院的研究者将报告对1.2万多例局限性前列腺癌患者的研究结果：调强放疗(IMRT)后续抗癌治疗的几率低于适形放疗；调强放疗的大肠毒性和髋部骨折发生率较低，但勃起功能障碍更多见。此外，质子治疗与IMRT相比，未能显著降低后续抗癌治疗的几率，且大肠毒性更多见。

·来自克利夫兰医院和Kaiser医疗集团的研究者将报告对137,427例不同分期前列腺癌患者中位随访71个月的结果：在3种常用治疗——前列腺切除术、外照射放疗(EBRT)和近距放疗——之中，EBRT与需要干预的胃肠道和生殖泌尿治疗相关毒性累计发生率最高相关，且费用亦最高。

同样将在2月2日报告的一项研究中，研究者对积极运动对前列腺基因表达的影响进行了分析，其结果可能有助于解释运动在减少肿瘤进展方面的益处。

·这项研究显示，在接受严密监测的前列腺癌低危人群中，积极运动(每周至少3 h)的男性与运动较不积极者相比，正常前列腺组织中有184个基因的表达存在差异。积极运动者的前列腺内有多种肿瘤抑制基因的表达上调，其DNA修复和细胞周期通路也出现了正性改变。

访问The Oncology Report可及时了解ASCO生殖泌尿肿瘤研讨会的最新资讯。

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