Response, Survival, and Long-Term Toxicity After Therapy With the Radiolabeled Somatostatin Analogue [90Y-DOTA]-TOC in Metastasized Neuroendocrine Cancers
Response, Survival, and Long-Term Toxicity After Therapy With the Radiolabeled Somatostatin Analogue [90Y-DOTA]-TOC in Metastasized Neuroendocrine Cancers
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DOI：
10.1200/jco.2010.33.7873
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发表时间：
2011-06-10
影响因子：
45.3
通讯作者：
Walter, Martin A.
中科院分区：
文献类型：
--
作者：
Imhof, Anna;Brunner, Philippe;Walter, Martin A.
PurposeTo investigate response, survival, and safety profile of the somatostatin-based radiopeptide (90)yttrium-labeled tetraazacyclododecane-tetraacetic acid modified Tyr-octreotide ([Y-90-DOTA]-TOC) in neuroendocrine cancers.Patients and MethodsIn a clinical phase II单中心开放标签试验，神经内分泌患者用[Y-90-DOTA] -TOC的重复循环处理癌症。每个循环由3.7GBQ/M（2）身体表面[Y-90-DOTA] -TOC的单个静脉注射。在肿瘤进展和/或永久性毒性的情况下，预定了其他周期。ResultSoverall，1,109例患者接受了2,472个循环[Y-90-DOTA] -TOC（中位数，两个；范围，每名患者1至10个周期）。在1,109例患者中，有378例（34.1％）经历了形态反应； 172（15.5％），生化反应；和329（29.7％），临床反应。在23个月的中位随访中，有491例患者（44.3％）死亡。较长的生存期与每个生存期相关：形态学（危险比[HR]，0.46; 95％CI，0.38至0.56;中位生存期，44.7 V 18.3个月； P <.001），生化（HR，0.75; 95％CI，0.59，0.59，0.59，0.59至0.96; 35.3 V 25.7个月； 0.68; 95％CI，0.56至0.82;总体而言，142例患者（12.8％）患有3至4级短暂的血液学毒性，103例患者（9.2％）经历了4至5级永久性肾脏毒性。多变量回归表明，初始成像研究中的肿瘤摄取可预测整体生存率（HR，0.45; 95％CI，0.29至0.69; P <.001），而初始肾脏的摄取可预测严重的肾脏毒性（HR，1.59，1.59，1.59 ; 95％CI，1.17至2.17;大型队列中[Y-90-DOTA] -TOC处理的结果。对[Y-90-DOTA] -TOC的反应与较长的生存有关。生长抑素受体成像可预测[Y-90-DOTA] -TOC治疗和肾脏毒性的发生后的生存。 J Clin Oncol 29：2416-2423。 （c）2011年美国临床肿瘤学会
PurposeTo investigate response, survival, and safety profile of the somatostatin-based radiopeptide (90)yttrium-labeled tetraazacyclododecane-tetraacetic acid modified Tyr-octreotide ([Y-90-DOTA]-TOC) in neuroendocrine cancers.Patients and MethodsIn a clinical phase II single-center open-label trial, patients with neuroendocrine cancers were treated with repeated cycles of [Y-90-DOTA]-TOC. Each cycle consisted of a single intravenous injection of 3.7GBq/m(2) body-surface [Y-90-DOTA]-TOC. Additional cycles were withheld in case of tumor progression and/or permanent toxicity.ResultsOverall, 1,109 patients received 2,472 cycles of [Y-90-DOTA]-TOC (median, two; range, one to 10 cycles per patient). Of the 1,109 patients, 378 (34.1%) experienced morphologic response; 172 (15.5%), biochemical response; and 329 (29.7%), clinical response. During a median follow-up of 23 months, 491 patients (44.3%) died. Longer survival was correlated with each: morphologic (hazard ratio [HR], 0.46; 95% CI, 0.38 to 0.56; median survival, 44.7 v 18.3 months; P < .001), biochemical (HR, 0.75; 95% CI, 0.59 to 0.96; 35.3 v 25.7 months; P = .023), and clinical response (HR, 0.68; 95% CI, 0.56 to 0.82; 36.8 v 23.5 months; P < .001). Overall, 142 patients (12.8%) developed grade 3 to 4 transient hematologic toxicities, and 103 patients (9.2%) experienced grade 4 to 5 permanent renal toxicity. Multivariable regression revealed that tumoral uptake in the initial imaging study was predictive for overall survival (HR, 0.45; 95% CI, 0.29 to 0.69; P < .001), whereas the initial kidney uptake was predictive for severe renal toxicity (HR, 1.59; 95% CI, 1.17 to 2.17; P = .003).ConclusionThis study documents the long-term outcome of [Y-90-DOTA]-TOC treatment in a large cohort. Response to [Y-90-DOTA]-TOC is associated with longer survival. Somatostatin receptor imaging is predictive for both survival after [Y-90-DOTA]-TOC treatment and occurrence of renal toxicity. J Clin Oncol 29:2416-2423. (C) 2011 by American Society of Clinical Oncology