Kwekkeboom Dik J, de Herder Wouter W, Kam Boen L, van Eijck Casper H, van Essen Martijn, Kooij Peter P, Feelders Richard A, van Aken Maarten O, Krenning Eric P
Department of Nuclear Medicine, Erasmus Medical Center, Dr Molewaterplein 40, 3015 GD Rotterdam, the Netherlands.
J Clin Oncol. 2008 May 1;26(13):2124-30. doi: 10.1200/JCO.2007.15.2553.
Despite the fact that most gastroenteropancreatic neuroendocrine tumors (GEPNETs) are slow-growing, median overall survival (OS) in patients with liver metastases is 2 to 4 years. In metastatic disease, cytoreductive therapeutic options are limited. A relatively new therapy is peptide receptor radionuclide therapy with the radiolabeled somatostatin analog [(177)Lu-DOTA(0),Tyr(3)]octreotate. Here we report on the toxicity and efficacy of this treatment, performed in over 500 patients.
Patients were treated up to a cumulative dose of 750 to 800 mCi (27.8-29.6 GBq), usually in four treatment cycles, with treatment intervals of 6 to 10 weeks. Toxicity analysis was done in 504 patients, and efficacy analysis in 310 patients.
Any hematologic toxicity grade 3 or 4 occurred after 3.6% of administrations. Serious adverse events that were likely attributable to the treatment were myelodysplastic syndrome in three patients, and temporary, nonfatal, liver toxicity in two patients. Complete and partial tumor remissions occurred in 2% and 28% of 310 GEPNET patients, respectively. Minor tumor response (decrease in size > 25% and < 50%) occurred in 16%. Median time to progression was 40 months. Median OS from start of treatment was 46 months, median OS from diagnosis was 128 months. Compared with historical controls, there was a survival benefit of 40 to 72 months from diagnosis.
Treatment with [(177)Lu-DOTA(0),Tyr(3)]octreotate has few adverse effects. Tumor response rates and progression-free survival compare favorably to the limited number of alternative treatment modalities. Compared with historical controls, there is a benefit in OS from time of diagnosis of several years.
尽管大多数胃肠胰神经内分泌肿瘤（GEPNETs）生长缓慢，但肝转移患者的中位总生存期（OS）为2至4年。在转移性疾病中，减瘤治疗选择有限。一种相对较新的治疗方法是使用放射性标记的生长抑素类似物[（177）Lu-DOTA（0），Tyr（3）]奥曲肽进行肽受体放射性核素治疗。在此，我们报告在500多名患者中进行的这种治疗的毒性和疗效。
患者接受累积剂量达750至800毫居里（27.8 - 29.6吉贝可）的治疗，通常分四个治疗周期进行，治疗间隔为6至10周。对504例患者进行了毒性分析，对310例患者进行了疗效分析。
3.6%的给药后出现3级或4级血液学毒性。可能归因于治疗的严重不良事件包括3例患者发生骨髓增生异常综合征，2例患者出现暂时性、非致命性肝毒性。在310例GEPNET患者中，完全缓解和部分缓解分别发生在2%和28%的患者中。16%的患者出现轻微肿瘤反应（肿瘤大小缩小>25%且<50%）。中位进展时间为40个月。从治疗开始的中位OS为46个月，从诊断开始的中位OS为128个月。与历史对照相比，从诊断开始有40至72个月的生存获益。
[（177）Lu-DOTA（0），Tyr（3）]奥曲肽治疗不良反应较少。肿瘤反应率和无进展生存期与有限的其他治疗方式相比具有优势。与历史对照相比，从诊断时起的OS有几年的获益。
