[Lu-DOTA,Tyr]奥曲肽挽救性肽受体放射性核素治疗支气管和胃肠胰腺神经内分泌肿瘤。
Salvage peptide receptor radionuclide therapy with [Lu-DOTA,Tyr]octreotate in patients with bronchial and gastroenteropancreatic neuroendocrine tumours.
机构信息
Department of Radiology & Nuclear Medicine, Erasmus Medical Centre, Rotterdam, The Netherlands.
Department of Internal Medicine, Erasmus Medical Centre, Rotterdam, The Netherlands.
出版信息
Eur J Nucl Med Mol Imaging. 2019 Mar;46(3):704-717. doi: 10.1007/s00259-018-4158-1. Epub 2018 Sep 28.
PURPOSE
Therapy with [Lu-DOTA,Tyr]octreotate is effective in patients with grade I/II metastasized and/or inoperable bronchial neuroendocrine tumour (NET) or gastroenteropancreatic NET (GEP-NET). In this study, we investigated the efficacy and safety of salvage treatment with [Lu-DOTA,Tyr]octreotate.
METHODS
Patients with progressive bronchial NET or GEP-NET were selected for re-(re)treatment if they had benefited from initial peptide receptor radionuclide therapy (I-PRRT) with a minimal progression-free survival (PFS) of 18 months. Patients received an additional cumulative dose of 14.8 GBq of [Lu-DOTA,Tyr]octreotate over two cycles per retreatment with PRRT (R-PRRT) or re-retreatment with PRRT (RR-PRRT).
RESULTS
The safety and efficacy analyses included 181 patients and 168 patients, respectively, with bronchial NET or GEP-NET. Overall median follow-up was 88.6 months (95% CI 79.0-98.2). Median cumulative doses were 44.7 GBq (range 26.3-46.4 GBq) during R-PRRT (168 patients) and 59.7 GBq (range 55.2-≤60.5 GBq) during RR-PRRT (13 patients). Objective response and stable disease, as best response, were observed in 26 patients (15.5%) and 100 patients (59.5%) following R-PRRT, and in 5 patients (38.5%) and 7 patients (53.8%) following RR-PRRT, respectively. Median PFS was 14.6 months (95% CI 12.4-16.9) following R-PRRT and 14.2 months (95% CI 9.8-18.5) following RR-PRRT. Combined overall survival (OS) after I-PRRT plus R-PRRT and RR-PRRT was 80.8 months (95% CI 66.0-95.6). Grade III/IV bone marrow toxicity occurred in 6.6% and 7.7% of patients after R-PRRT and RR-PRRT, respectively. Salvage therapy resulted in a significantly longer OS in patients with bronchial NET, GEP-NET and midgut NET than in a nonrandomized control group. The total incidence of acute myeloid leukaemia (AML) and myelodysplastic syndrome (MDS) was 2.2%. No PRRT-related grade III/IV nephrotoxicity was observed.
CONCLUSION
A cumulative dose of up to 60.5 GBq salvage PRRT with [Lu-DOTA,Tyr]octreotate is safe and effective in patients with progressive disease (relapse-PD) following I-PRRT with [Lu-DOTA,Tyr]octreotate. Safety appears similar to that of I-PRRT as no higher incidence of AML or MDS was observed. No grade III/IV renal toxicity occurred after retreatment.
目的
[Lu-DOTA,Tyr]奥曲肽治疗 I/II 级转移性和/或不可手术的支气管神经内分泌肿瘤（NET）或胃肠胰腺神经内分泌肿瘤（GEP-NET）患者是有效的。在这项研究中，我们研究了[Lu-DOTA,Tyr]奥曲肽挽救治疗的疗效和安全性。
方法
如果初始肽受体放射性核素治疗（I-PRRT）有最小无进展生存期（PFS）≥18 个月的进展性支气管 NET 或 GEP-NET 患者受益，则选择进行重新（再）治疗。患者在每个 PRRT 再治疗（R-PRRT）或 PRRT 再治疗（RR-PRRT）周期中接受 14.8GBq 的累积剂量[Lu-DOTA,Tyr]奥曲肽。
结果
安全性和疗效分析分别纳入了 181 例和 168 例支气管 NET 或 GEP-NET 患者。总体中位随访时间为 88.6 个月（95%CI 79.0-98.2）。中位累积剂量分别为 R-PRRT 期间 44.7GBq（范围 26.3-46.4GBq）（168 例患者）和 RR-PRRT 期间 59.7GBq（范围 55.2-≤60.5GBq）（13 例患者）。R-PRRT 后观察到最佳反应的客观缓解和疾病稳定分别为 26 例（15.5%）和 100 例（59.5%），RR-PRRT 后分别为 5 例（38.5%）和 7 例（53.8%）。R-PRRT 后 PFS 的中位时间为 14.6 个月（95%CI 12.4-16.9），RR-PRRT 后为 14.2 个月（95%CI 9.8-18.5）。I-PRRT 加 R-PRRT 和 RR-PRRT 后的总生存（OS）为 80.8 个月（95%CI 66.0-95.6）。R-PRRT 和 RR-PRRT 后骨髓毒性分别为 III/IV 级的患者分别为 6.6%和 7.7%。与非随机对照组相比，支气管 NET、GEP-NET 和中肠 NET 患者的挽救性治疗导致 OS 显著延长。急性髓系白血病（AML）和骨髓增生异常综合征（MDS）的总发生率为 2.2%。未观察到与 PRRT 相关的 III/IV 级肾毒性。
结论
在接受[Lu-DOTA,Tyr]奥曲肽治疗后发生疾病进展（复发-PD）的患者中，累积剂量高达 60.5GBq 的挽救性 PRRT 联合[Lu-DOTA,Tyr]奥曲肽治疗是安全有效的。安全性似乎与 I-PRRT 相似，因为没有观察到 AML 或 MDS 的发生率更高。在重新治疗后没有发生 III/IV 级肾毒性。
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