J Nuc Med：新疗法延长前列腺癌病人的生命

佛罗里达州迈阿密海滩——有已经扩散到骨的晚期肿瘤的前列腺癌病人的生存机会很差。参加美国核医学学会（Society of Nuclear Medicine）2012年会的科研人员说，一种新型放射性同位素疗法可能会让患这种病的病人活得更长。

骨骼系统是前列腺癌病人的第一位的转移部位。癌的骨转移发生在原发癌通过血液被输送到骨并且在那里发育的时候。这是一项对氯化镭-223或Ra-223的放射性同位素的III期研究，它使用对于肿瘤致命的非常强有力的α粒子找到癌的骨转移。这种强有力的药物的α粒子的穿透范围短，不会伤害附近的健康组织和关键的骨髓。它最初是作为去势抵抗性前列腺癌的疗法加以研究的，这是一种晚期癌症，通常以广泛的骨骼癌转移为特征，能耐受治疗。相关研究成果刊登在国际杂志The Journal of Nuclear Medicine上。

“这是对一种新疗法的一个关键的研究，这种疗法有可能为晚期前列腺癌病人提供更好的护理标准，”英国伦敦大学国王学院以及伦敦Guy与圣托马斯医院的临床治疗核医学教授Val Lewington说。“镭-223提供了治疗癌的骨转移的一种全新方法。它系统化地同时治疗该病的多个位置，而且通常耐受性非常好。严重的副作用不常见，而且甚至对于已经进行过深度预先化疗治疗的病人的骨髓抑制风险也较低。

美国国立癌症研究所的数据表明，今年在美国预计将诊断出24，1740例前列腺癌新病例，而2，8170人将死于该病。在过去25年里，已经开发出了许多以骨为靶标的药物，但是它们起到的更多的是一种缓和效应，治疗疼痛，但未必延长病人的生命。

患去势抵抗性前列腺癌的男性通常在被诊断出患病之后能存活3到5年。这项双盲随机化研究能够证明用镭-223或安慰剂治疗的921位病人之中的获得这种药物的病人平均多生存了3个月。治疗是以间隔4周注射6次的方式进行的。除了延长存活期，那些用镭-223治疗的人的癌的骨转移造成的并发症的出现也被推迟了。用称为闪烁显像术和正电子发射断层成像的分子成像技术进行了治疗监测，它们提供了关于生物过程的信息，包括了那些参与癌性肿瘤的生物过程的信息。

一个扩展了的获取项目已经在美国展开，一个类似的项目预计将于2012年在欧洲展开。进一步的临床试验也正在被考虑当中。将于2012年中期在美国和欧洲寻求获得正式的管理批准。

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Radium-223 chloride: Radiation safety, tolerability, and survival gain in patients with castration-resistant prostate cancer (CRPC) and bone metastases

Valerie Lewington1, Roy Lamey2, Karin Staudacher3 and Nicholas Vogelzang2

Abstract No. 222 Objectives: Radium-223 chloride (Ra-223) targets bone metastases with high LET, short range (<100μm) alpha-particles. The phase III, double-blind, randomized, international ALSYMPCA study compared Ra-223 plus best standard of care (BSC) vs placebo plus BSC in CRPC patients with bone metastases. The radiation safety and phase III clinical results using Ra-223 are described. Methods: The physical properties of Ra-223 were assessed to establish radiation protection parameters for safe use. Eligible ALSYMPCA patients had confirmed CRPC with 2 bone metastases, no known visceral disease, and were post-docetaxel or unfit for docetaxel. The primary endpoint was overall survival (OS). After randomization (2:1), 922 pts (Ra-223, n=615; placebo, n=307) received 6 injections of Ra-223 (50 kBq/kg IV) every 4 weeks or matching placebo. Results: The 11.4 day physical T1/2 of Ra-223 was sufficient for preparation, distribution, and administration. The short penetration of alpha radiation avoided requirements for complex shielding. Treatment was delivered on an outpatient basis. No specific radiation protection restrictions were required. Standard equipment was used for contamination monitoring. A planned interim analysis of ALSYMPCA (n=809) showed that Ra-223 improved median OS vs placebo (14.0 vs 11.2 mo, respectively; two-sided P=.00185; HR=.695; 95% CI, .552-.875). Safety and tolerability of Ra-223 were favorable, with low myelosuppression (1.8% vs 0.8% grade 3/4 neutropenia in Ra-223 and placebo groups, respectively). Conclusions: Ra-223 is safe and straightforward to administer using conventional nuclear medicine equipment. Few radiation protection limitations are required post-therapy. ALSYMPCA demonstrated significantly improved OS and very low toxicity, suggesting that Ra-223 may provide a new standard of care for patients with CRPC and bone metastases. Research Support: Algeta AS