骨靶向镭-223治疗有症状的激素难治性前列腺癌：一项随机、多中心、安慰剂对照的II期研究。
Bone-targeted radium-223 in symptomatic, hormone-refractory prostate cancer: a randomised, multicentre, placebo-controlled phase II study.
作者信息
Nilsson Sten, Franzén Lars, Parker Christopher, Tyrrell Christopher, Blom René, Tennvall Jan, Lennernäs Bo, Petersson Ulf, Johannessen Dag C, Sokal Michael, Pigott Katharine, Yachnin Jeffrey, Garkavij Michael, Strang Peter, Harmenberg Johan, Bolstad Bjørg, Bruland Oyvind S
机构信息
Karolinska Hospital, Stockholm, Sweden.
出版信息
Lancet Oncol. 2007 Jul;8(7):587-94. doi: 10.1016/S1470-2045(07)70147-X.
BACKGROUND
The alpha-emitter radium-223 ((223)Ra) is a bone-seeking radionuclide studied as a new treatment for patients with bone metastases from hormone-refractory prostate cancer. We aimed to study mature outcomes from a randomised, multicentre, phase II study of (223)Ra.
METHODS
Patients with hormone-refractory prostate cancer and bone pain needing external-beam radiotherapy were assigned to four intravenous injections of (223)Ra (50 kBq/kg, 33 patients) or placebo (31 patients), given every 4 weeks. Primary endpoints were change in bone-alkaline phosphatase (ALP) concentration and time to skeletal-related events (SREs). Secondary endpoints included toxic effects, time to prostate-specific-antigen (PSA) progression, and overall survival. All tests were done at a 5% significance level, based on intention to treat.
FINDINGS
Median relative change in bone-ALP during treatment was -65.6% (95% CI -69.5 to -57.7) and 9.3% (3.8-60.9) in the (223)Ra group and placebo groups, respectively (p<0.0001, Wilcoxon ranked-sums test). Hazard ratio for time to first SRE, adjusted for baseline covariates, was 1.75 (0.96-3.19, p=0.065, Cox regression). Haematological toxic effects did not differ significantly between two groups. No patient discontinued (223)Ra because of treatment toxicity. Median time to PSA progression was 26 weeks (16-39) versus 8 weeks (4-12; p=0.048) for (223)Ra versus placebo, respectively. Median overall survival was 65.3 weeks (48.7-infinity) for (223)Ra and 46.4 weeks (32.1-77.4) for placebo (p=0.066, log rank). The hazard ratio for overall survival, adjusted for baseline covariates was 2.12 (1.13-3.98, p=0.020, Cox regression).
INTERPRETATION
(223)Ra was well tolerated with minimum myelotoxicity, and had a significant effect on bone-ALP concentrations. Larger clinical trials are warranted to study (223)Ra on the prevention of SREs and on overall survival in patients with hormone-refractory prostate cancer. Bone-targeting properties of (223)Ra could also potentially be used for treating skeletal metastasis from other primary cancers.
背景
发射α粒子的镭-223（²²³Ra）是一种亲骨性放射性核素，正作为激素难治性前列腺癌骨转移患者的一种新治疗方法进行研究。我们旨在研究²²³Ra的一项随机、多中心、II期研究的成熟结果。
方法
将有激素难治性前列腺癌且骨痛需要外照射放疗的患者分为两组，分别接受四次静脉注射²²³Ra（50 kBq/kg，33例患者）或安慰剂（31例患者），每4周注射一次。主要终点为骨碱性磷酸酶（ALP）浓度的变化和至骨相关事件（SREs）的时间。次要终点包括毒性作用、前列腺特异性抗原（PSA）进展时间和总生存期。所有检验均基于意向性分析，显著性水平设定为5%。
结果
²²³Ra组和安慰剂组治疗期间骨ALP的中位相对变化分别为-65.6%（95%CI -69.5至-57.7）和9.3%（3.8 - 60.9）（p<0.0001，Wilcoxon秩和检验）。经基线协变量校正后，至首次SRE时间的风险比为1.75（0.96 - 3.19，p = 0.065，Cox回归）。两组血液学毒性作用无显著差异。没有患者因治疗毒性而停用²²³Ra。²²³Ra组和安慰剂组PSA进展的中位时间分别为26周（16 - 39）和8周（4 - 12；p = 0.048）。²²³Ra组和安慰剂组的中位总生存期分别为65.3周（48.7 - 无穷大）和46.4周（32.1 - 77.4）（p = 0.066，对数秩检验）。经基线协变量校正后，总生存期的风险比为2.12（1.13 - 3.98，p = 0.020，Cox回归）。
解读
²²³Ra耐受性良好，骨髓毒性最小，对骨ALP浓度有显著影响。有必要开展更大规模的临床试验，研究²²³Ra对激素难治性前列腺癌患者预防SREs和总生存期的影响。²²³Ra的骨靶向特性也可能用于治疗其他原发性癌症的骨转移。
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