Kesavan Murali, Turner J Harvey
School of Medicine and Pharmacology, The University of Western Australia , Crawley, Australia .
Cancer Biother Radiopharm. 2016 Aug;31(6):189-98. doi: 10.1089/cbr.2016.2035. Epub 2016 Jul 15.
This review of the literature, and the authors' own decade of experience with lutetium-177-octreotate-capecitabine±temozolomide peptide receptor radionuclide therapy (PRRT)-chemotherapy of GEPNETs, analyses the risk of both short- and long-term hematotoxicity.
Myelodysplastic syndrome (MDS) and acute leukemia (AL) have been associated with PRRT in heavily pretreated patients with a history of exposure to alkylating agents. Commenced 15 years ago, PRRT is now becoming established as first- and second-line therapy for gastroentero pancreatic neuroendocrine tumors (GEPNETs), and early treatment minimizes myelotoxicity, which is the most significant potential adverse event following PRRT.
Sixteen key articles involving primary research were identified. A total of 2225 patients were treated (2104 treated with PRRT monotherapy and 121 with PRRT combined with chemotherapy). The average age of patients in these studies ranged from 53 to 64 years with median duration of follow-up ranging from 6 to 62 months. Short-term myelotoxicity was observed in 221 patients (10%), occurring in 213 of 2104 patients treated with PRRT monotherapy and 8 of 121 patients treated with PRRT combined with chemotherapy. Acute toxicity manifested as modest self-limited grade 3/4 toxicity (CTCAE or WHO), most often affecting platelets during the first cycle of treatment. Toxicity manifesting early was easily managed with dose modification or therapy cessation and was ameliorated by appropriate patient selection. MDS/AL was a rare stochastic event occurring in 32 (1.4%) patients. Where bone marrow biopsy was performed, cases of MDS displayed cytogenetic abnormalities, consistent with secondary MDS. Factors associated with myelotoxicity included age >70 years, impaired renal function, baseline cytopenias, prior number of therapies, prior chemotherapy (alkylating agents), and prior radiotherapy.
Early therapy with PRRT-containing regimens improves outcomes, minimizes myelotoxicity, and renders the risk of MDS and AL negligible.
本文献综述以及作者自身在使用镥-177-奥曲肽-卡培他滨±替莫唑胺对胃肠胰神经内分泌肿瘤（GEPNETs）进行肽受体放射性核素治疗（PRRT）-化疗方面的十年经验，分析了短期和长期血液毒性风险。
骨髓增生异常综合征（MDS）和急性白血病（AL）与接受过大量预处理且有烷化剂暴露史的患者接受PRRT治疗有关。PRRT于15年前开始应用，目前正成为胃肠胰神经内分泌肿瘤（GEPNETs）一线和二线治疗方法，早期治疗可将骨髓毒性降至最低，而骨髓毒性是PRRT后最显著的潜在不良事件。
确定了16篇涉及原发性研究的关键文章。共治疗了2225例患者（2104例接受PRRT单一疗法治疗，121例接受PRRT联合化疗治疗）。这些研究中患者的平均年龄在53至64岁之间，中位随访时间在6至62个月之间。221例患者（10%）出现短期骨髓毒性，其中2104例接受PRRT单一疗法治疗的患者中有213例出现，121例接受PRRT联合化疗治疗的患者中有8例出现。急性毒性表现为中度自限性3/4级毒性（根据CTCAE或WHO标准），最常影响治疗第一个周期的血小板。早期出现的毒性通过剂量调整或停止治疗很容易控制，并且通过适当的患者选择可得到改善。MDS/AL是一种罕见的随机事件，发生在32例（1.4%）患者中。在进行骨髓活检的病例中，MDS病例显示细胞遗传学异常，与继发性MDS一致。与骨髓毒性相关的因素包括年龄>70岁、肾功能受损、基线血细胞减少、既往治疗次数、既往化疗（烷化剂）和既往放疗。
含PRRT方案的早期治疗可改善预后，将骨髓毒性降至最低，并使MDS和AL的风险可忽略不计。
