Somatostatin-based radiotherapy with [90Y-DOTA]-TOC in neuroendocrine tumors: long-term outcome of a phase I dose escalation study.
Somatostatin-based radiotherapy with [90Y-DOTA]-TOC in neuroendocrine tumors: long-term outcome of a phase I dose escalation study.
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DOI：
10.1186/1479-5876-11-17
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发表时间：
2013-01-15
影响因子：
7.4
通讯作者：
Walter MA
中科院分区：
文献类型：
--
作者：
Marincek N;Jörg AC;Brunner P;Schindler C;Koller MT;Rochlitz C;Müller-Brand J;Maecke HR;Briel M;Walter MA
我们描述了在转移性神经内分泌肿瘤患者中使用[90Y-DOTA]-TOC进行生长抑素受体靶向治疗后临床引入和剂量递增的长期结果。在一项临床I期剂量递增研究中，我们治疗了[90Y-DOTA]-TOC活性增加的患者。采用多变量Cox回归和竞争风险回归比较不同剂量方案的疗效和毒性。总共招募了359名患者；低剂量组60例（中位数：2.4 GBq/周期，范围0.9-7.8 GBq/周期），中剂量组77例（中位数：3.3 GBq/周期，范围2.0-7.4 GBq/周期），高剂量组222例（中位数：6.7 GBq/周期，范围3.7-8.1 GBq/周期）[90Y-DOTA]-TOC治疗。1 ~ 4级血液毒性发生率分别为65.0%、64.9%和74.8%；4/5级肾毒性发生率分别为8.4%、6.5%和14.0%，中位生存期分别为39（1-158）个月、34（1-118）个月和29（1-113）个月。高剂量方案与肾毒性风险增加相关（风险比：3.12 (1.13-8.59)vs中剂量，p = 0.03），总生存期较短（风险比：2.50 (1.08-5.79)vs低剂量，p = 0.03）。[90Y-DOTA]-TOC活性的增加可能与血液毒性的增加有关。[90Y-DOTA]-TOC的剂量相关血液毒性谱可以帮助预先存在血液毒性的患者调整[90Y-DOTA]-TOC。长期预后结果表明，分级[90Y-DOTA]-TOC治疗可减少肾毒性并提高总生存率。多:NCT00978211
We describe the long-term outcome after clinical introduction and dose escalation of somatostatin receptor targeted therapy with [90Y-DOTA]-TOC in patients with metastasized neuroendocrine tumors. In a clinical phase I dose escalation study we treated patients with increasing [90Y-DOTA]-TOC activities. Multivariable Cox regression and competing risk regression were used to compare efficacy and toxicities of the different dosage protocols. Overall, 359 patients were recruited; 60 patients were enrolled for low dose (median: 2.4 GBq/cycle, range 0.9-7.8 GBq/cycle), 77 patients were enrolled for intermediate dose (median: 3.3 GBq/cycle, range: 2.0-7.4 GBq/cycle) and 222 patients were enrolled for high dose (median: 6.7 GBq/cycle, range: 3.7-8.1 GBq/cycle) [90Y-DOTA]-TOC treatment. The incidences of hematotoxicities grade 1–4 were 65.0%, 64.9% and 74.8%; the incidences of grade 4/5 kidney toxicities were 8.4%, 6.5% and 14.0%, and the median survival was 39 (range: 1–158) months, 34 (range: 1–118) months and 29 (range: 1–113) months. The high dose protocol was associated with an increased risk of kidney toxicity (Hazard Ratio: 3.12 (1.13-8.59) vs. intermediate dose, p = 0.03) and a shorter overall survival (Hazard Ratio: 2.50 (1.08-5.79) vs. low dose, p = 0.03). Increasing [90Y-DOTA]-TOC activities may be associated with increasing hematological toxicities. The dose related hematotoxicity profile of [90Y-DOTA]-TOC could facilitate tailoring [90Y-DOTA]-TOC in patients with preexisting hematotoxicities. The results of the long-term outcome suggest that fractionated [90Y-DOTA]-TOC treatment might allow to reduce renal toxicity and to improve overall survival. ClinicalTrials.gov number:NCT00978211
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影响因子：
6.1
作者：
BAUER, W;BRINER, U;PLESS, J
通讯作者：
PLESS, J
影响因子：
6.2
作者：
Iten, Fabienne;Muller, Beat;Walter, Martin A.
通讯作者：
Walter, Martin A.
影响因子：
5.8
作者：
Oomen, SPMA;Hofland, LJ;Touw, IP
通讯作者：
Touw, IP
影响因子：
45.3
作者：
Imhof, Anna;Brunner, Philippe;Walter, Martin A.
通讯作者：
Walter, Martin A.
影响因子：
2
作者：
Putter, H.;Fiocco, M.;Geskus, R. B.
通讯作者：
Geskus, R. B.