伴随 177Lu-DOTATATE 和卡培他滨治疗晚期神经内分泌肿瘤患者：长期结果、毒性、生存和生活质量研究。

Concomitant 177Lu-DOTATATE and Capecitabine Therapy in Patients With Advanced Neuroendocrine Tumors: A Long-term-Outcome, Toxicity, Survival, and Quality-of-Life Study.

机构信息

From the Departments of *Nuclear Medicine, and †Medical Oncology, All India Institute of Medical Sciences, New Delhi, India.

出版信息

Clin Nucl Med. 2017 Nov;42(11):e457-e466. doi: 10.1097/RLU.0000000000001816.

DOI:10.1097/RLU.0000000000001816

PMID:28872545

Abstract

PURPOSE

The purpose of this study was to evaluate the outcome, toxicity, survival, and quality of life in patients with advanced neuroendocrine tumors.

METHODS

One hundred sixty-seven patients were enrolled in the study. All patients underwent baseline Ga-DOTANOC PET/CT scans. Lu-DOTATATE therapy was administered quarterly along with oral capecitabine therapy in group 1 patients (n = 88), whereas group 2 patients (n = 79) were treated only with Lu-DOTATATE. Hematologic, kidney function, liver function tests and chromogranin A levels were recorded before and after therapy at 2-week, 4-week, and 3-month intervals. Biochemical and morphological responses were assessed with the trend in chromogranin A levels and Response Evaluation Criteria in Solid Tumors 1.1 criteria, respectively.

RESULTS

There was no significant difference in the hemoglobin levels after Lu-DOTATATE therapy (P = 0.4892). In most patients, there was a decrease in the platelet levels; however, all the patients had platelet counts greater than 100,000/μL with no platelet toxicity. There was no toxicity related to leukocytes. Two patients showed renal insufficiencies. No hepatotoxicity was observed in any of the patients. According to Response Evaluation Criteria in Solid Tumors 1.1 criteria, in group 1 patients, the response was partial response in 34% of the patients, stable disease in 50.2%, and progressive disease in 6.8% versus partial response in 6.3%, stable disease in 60.9%, and progressive disease in 26.5% among group 2 patients. The median overall survival (OS) and progression-free survival (PFS) was not reached in group 1 patients. The median OS and PFS in group 2 patients were 48 months. Ki-67 tumor proliferation index was significantly associated with increased risk of disease progression.

CONCLUSIONS

Addition of capecitabine therapy with Lu-DOTATATE therapy lengthens the OS and PFS. Patients with aggressive disease may benefit from this synergetic therapeutic approach.

摘要

目的

本研究旨在评估晚期神经内分泌肿瘤患者的治疗效果、毒性、生存和生活质量。

方法

本研究共纳入 167 例患者。所有患者均行基线 Ga-DOTANOC PET/CT 扫描。第 1 组（n=88）患者接受 Lu-DOTATATE 治疗，并联合卡培他滨口服治疗，每季度一次；第 2 组（n=79）患者仅接受 Lu-DOTATATE 治疗。治疗前后每 2 周、4 周和 3 个月分别记录患者的血液学、肾功能、肝功能检查和嗜铬粒蛋白 A 水平。采用嗜铬粒蛋白 A 水平变化趋势和实体瘤疗效评价标准 1.1 标准评估生化和形态学反应。

结果

Lu-DOTATATE 治疗后血红蛋白水平无显著差异（P=0.4892）。大多数患者血小板计数下降，但所有患者血小板计数均>100000/μL，且无血小板毒性。白细胞无毒性相关变化。2 例患者出现肾功能不全。无患者发生肝毒性。根据实体瘤疗效评价标准 1.1 标准，第 1 组患者中，部分缓解率为 34%，疾病稳定率为 50.2%，进展率为 6.8%，而第 2 组患者中，部分缓解率为 6.3%，疾病稳定率为 60.9%，进展率为 26.5%。第 1 组患者中位总生存期（OS）和无进展生存期（PFS）均未达到，第 2 组患者中位 OS 和 PFS 为 48 个月。Ki-67 肿瘤增殖指数与疾病进展风险增加显著相关。