Dose escalation of an Evans blue-modified radiolabeled somatostatin analog 177Lu-DOTA-EB-TATE in the treatment of metastatic neuroendocrine tumors
Dose escalation of an Evans blue-modified radiolabeled somatostatin analog 177Lu-DOTA-EB-TATE in the treatment of metastatic neuroendocrine tumors
复制标题
伊文思蓝修饰的放射性标记生长抑素类似物 Lu-177-DOTA-EB-TATE 治疗转移性神经内分泌肿瘤的剂量递增
DOI：
10.1007/s00259-019-04530-1
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发表时间：
2020-04-01
影响因子：
9.1
通讯作者：
Chen, Xiaoyuan
中科院分区：
文献类型：
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作者：
Liu, Qingxing;Cheng, Yuejuan;Chen, Xiaoyuan
目的：评价177 Lu-DOTA-EB-TATE（伊文思蓝修饰的生长抑素类似物）递增剂量治疗进行性转移性神经内分泌肿瘤（NETs）的安全性和有效性（n = 6，43 ± 12岁）施用约3.7GBq（100 mCi）177 Lu-DOTATATE作为对照; B组（n = 7，55 ± 7岁），给予约1.11 GBq（30 mCi）177 Lu-DOTA-EB-TATE; C组D组（n = 6，55 ± 10岁）给予约1.85 GBq（50 mCi）177 Lu-DOTA-EB-TATE; D组（n = 14，50 ± 10岁）给予约3.7 GBq（100 mCi）177 Lu-DOTA-EB-TATE。根据CTCAE v.5.0对治疗相关不良事件进行分级。在基线和治疗后2-3个月进行68 Ga-DOTATATE PET/CT评估反应。在A-C组治疗期间或治疗后未观察到CTC 3/4血液毒性、肾毒性或肝毒性。D组2例曾接受多疗程化疗的患者出现CTC-3血液毒性反应。治疗1个周期后，C组和D组SUVmax分别下降（Δ% =-17.4 ± 29.3%）和（Δ% =-15.1 ± 39.1%），B组SUVmax明显升高（Δ% = 30.0 ± 68.0%），A组SUVmax轻度升高（Δ% = 5.4 ± 45.9%）。参照EORTC标准，A、B、C和D组分别有16.7%（1/6）、0%（0/7）、50%（3/6）和50%（7/14）被评价为部分缓解。当选择基线SUVmax范围为15 - 40的病变时，B组的SUVmax未显示显著降低（Δ% = - 7.3 ± 24.5%）（P = 0.214），C组显著降低D组（Δ% =-34.9 ± 12.4%）（P = 0.001），D组（Δ% =-17.9 ± 19.7%）（P = 0.012）较A组（Δ% = 8.4 ± 48.8%）增加。EBTATE组（B-D组合并）的SUVmax较TATE组显著降低（Δ% =-19.0 ± 21.5%）（P = 0.045）。1.85 GBq（50 mCi）和3.7 GBq（100 mCi）剂量似乎比1.11 GBq（30 mCi）剂量更有效。试验注册：使用177 Lu-DOTA-EB-TATE治疗晚期神经内分泌肿瘤患者（NCT 03478358）网址：https://register.clinicaltrials.gov/prs/app/action/ViewOrUnrelease? uid=U0001JRW&ts=13&sid=S0007RNX&cx=y3yqv4。
Purpose:To evaluate the safety and efficacy of177Lu-DOTA-EB-TATE, a radiolabeled somatostatin analog modified by Evans blue, at escalating doses, was used to increase tumor retention in patients with progressive metastatic neuroendocrine tumors (NETs).Methods:Thirty-three patients with metastatic NETs were prospectively enrolled into four groups: group A (n = 6, 43 ± 12 years) administered approximately 3.7 GBq (100 mCi)177Lu-DOTATATE as controls; group B (n = 7, 55 ± 7 years) administered approximately 1.11 GBq (30 mCi)177Lu-DOTA-EB-TATE; group C (n = 6, 55 ± 10 years) administered approximately 1.85 GBq (50 mCi)177Lu-DOTA-EB-TATE; group D (n = 14, 50 ± 10 years) administered approximately 3.7 GBq (100 mCi)177Lu-DOTA-EB-TATE. Treatment-related adverse events were graded according to the CTCAE v.5.0.68Ga-DOTATATE PET/CT were performed at baseline and 2-3 months after treatment for response evaluation.Results:Administration was well tolerated. No CTC 3/4 hematotoxicity, nephrotoxicity, or hepatotoxicity was observed during or after treatment in groups A-C. In group D, CTC-3 hematotoxicity was recorded in 2 patients with multicourse chemotherapy previously. After one-cycle treatment, the SUVmax decreased in group C (Δ% = - 17.4 ± 29.3%) and group D (Δ% = - 15.1 ± 39.1%), but greatly increased in group B (Δ% = 30.0 ± 68.0%) and mildly increased in group A (Δ% = 5.4 ± 45.9%). Referring to EORTC criteria, 16.7% (1/6), 0% (0/7), 50% (3/6), and 50% (7/14) were evaluated as partial response in groups A, B, C, and D, respectively. When selecting lesions with comparable baseline SUVmax ranging from 15 to 40, SUVmax showed no significant decrease in group B (Δ% = - 7.3 ± 24.5%) (P = 0.214), significant decrease in group C (Δ% = - 34.9 ± 12.4%) (P = 0.001), and in group D (Δ% = - 17.9 ± 19.7%) (P = 0.012) as compared with group A with increased SUVmax (Δ% = 8.4 ± 48.8%). SUVmax significantly decreased in the EBTATE groups (groups B-D combined) (Δ% = - 19.0 ± 21.5%) as compared with the TATE group (P = 0.045).Conclusion:177Lu-DOTA-EB-TATE is well tolerated and is more effective than177Lu-DOTATATE. Both 1.85 GBq (50 mCi) and 3.7 GBq (100 mCi) doses appear to be more effective than 1.11 GBq (30 mCi) dose. Further investigation with more cycles of177Lu-DOTA-EB-TATE treatment and longer follow-up is warranted.Trial registration:Treatment Using 177Lu-DOTA-EB-TATE in Patients with Advanced Neuroendocrine Tumors (NCT03478358). URL: https://register.clinicaltrials.gov/prs/app/action/ViewOrUnrelease?uid=U0001JRW&ts=13&sid=S0007RNX&cx=y3yqv4.