Institute of Nuclear Medicine, University Hospital Basel, CH.
J Transl Med. 2013 Jan 15;11:17. doi: 10.1186/1479-5876-11-17.
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).
我们描述了生长抑素受体靶向治疗[90Y-DOTA]-TOC 在转移性神经内分泌肿瘤患者中的临床应用和剂量递增的长期结果。
在一项临床 I 期剂量递增研究中，我们用递增的[90Y-DOTA]-TOC 活性治疗患者。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。
共有 359 例患者入组；60 例患者接受低剂量（中位数：2.4GBq/周期，范围 0.9-7.8GBq/周期），77 例患者接受中剂量（中位数：3.3GBq/周期，范围：2.0-7.4GBq/周期），222 例患者接受高剂量（中位数：6.7GBq/周期，范围：3.7-8.1GBq/周期）[90Y-DOTA]-TOC 治疗。血液学毒性 1-4 级的发生率为 65.0%、64.9%和 74.8%；4/5 级肾毒性的发生率为 8.4%、6.5%和 14.0%，中位生存期为 39（范围：1-158）个月、34（范围：1-118）个月和 29（范围：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）比中间剂量，p=0.03），总生存期缩短（风险比：2.50（1.08-5.79）比低剂量，p=0.03）。
增加[90Y-DOTA]-TOC 活性可能与血液学毒性增加有关。[90Y-DOTA]-TOC 的剂量相关血液学毒性特征可以帮助在存在血液学毒性的患者中定制[90Y-DOTA]-TOC。长期结果表明，分次[90Y-DOTA]-TOC 治疗可能降低肾毒性并提高总生存率。（临床试验注册号：NCT00978211）。
