7.4GBq（90）Y-奥曲肽治疗后神经内分泌肿瘤的肿瘤反应及临床获益

Tumor response and clinical benefit in neuroendocrine tumors after 7.4 GBq (90)Y-DOTATOC.

作者信息

Waldherr Christian, Pless Miklos, Maecke Helmut R, Schumacher Tilmann, Crazzolara Armin, Nitzsche Egbert U, Haldemann Andreas, Mueller-Brand Jan

机构信息

PET Center, Institute of Nuclear Medicine, University Hospital, University of Basel, Basel, Switzerland.

出版信息

J Nucl Med. 2002 May;43(5):610-6.

PMID:11994522

Abstract

UNLABELLED

The aim of this prospective phase II study was to evaluate the tumor response of neuroendocrine tumors to high-dose targeted irradiation with 7.4 GBq/m(2) of the radiolabeled somatostatin analog (90)Y-1,4,7,10-tetra-azacyclododecan-4,7,10-tricarboxy-methyl-1-yl-acetyl-D-Phe-Tyr(3)-octreotide (DOTATOC). In addition, we investigated the clinical benefit of (90)Y-DOTATOC regarding the malignant carcinoid syndrome and tumor-associated pain.

METHODS

Thirty-nine patients (mean age, 55 y) with progressive neuroendocrine gastroenteropancreatic and bronchial tumors were included. The treatment consisted of 4 equal intravenous injections of a total of 7.4 GBq/m(2) (90)Y-DOTATOC, administered at intervals of 6 wk. After each treatment cycle, a standardized clinical benefit assessment using the National Cancer Institute grading criteria (NCI-CTC) was performed.

RESULTS

The objective response rate according to World Health Organization (WHO) criteria was 23%. For endocrine pancreatic tumors (13 patients), the objective response rate was 38%. Complete remissions were found in 5% (2/39), partial remissions in 18% (7/39), stable disease in 69% (27/39), and progressive disease in 8% (3/39). A significant reduction of clinical symptoms could be found in 83% of patients with diarrhea, in 46% of patients with flush, in 63% of patients with wheezing, and in 75% of patients with pellagra. The overall clinical benefit was 63%. All responses (both clinical benefit and WHO response) were ongoing for the duration of follow-up (median, 6 mo; range, 2-12 mo). Side effects were grade 3 or 4 (NCI-CTC) lymphocytopenia in 23%, grade 3 anemia in 3%, and grade 2 renal insufficiency in 3%.

CONCLUSION

High-dose targeted radiotherapy with 7.4 GBq/m(2) (90)Y-DOTATOC is a well-tolerated treatment for neuroendocrine tumors, with remarkable clinical benefit and objective response.

摘要

未标记

本前瞻性II期研究的目的是评估神经内分泌肿瘤对高剂量靶向照射的肿瘤反应，该照射使用7.4 GBq/m²的放射性标记生长抑素类似物（90）Y-1,4,7,10-四氮杂环十二烷-4,7,10-三羧甲基-1-基-乙酰基-D-苯丙氨酸-酪氨酸（3）-奥曲肽（DOTATOC）。此外，我们研究了（90）Y-DOTATOC对恶性类癌综合征和肿瘤相关疼痛的临床益处。

方法

纳入39例（平均年龄55岁）进展性神经内分泌胃肠胰腺和支气管肿瘤患者。治疗包括分4次静脉注射，共7.4 GBq/m²的（90）Y-DOTATOC，间隔6周给药。每个治疗周期后，使用美国国立癌症研究所分级标准（NCI-CTC）进行标准化临床益处评估。

结果

根据世界卫生组织（WHO）标准，客观缓解率为23%。对于内分泌胰腺肿瘤（13例患者），客观缓解率为38%。完全缓解率为5%（2/39），部分缓解率为18%（7/39），疾病稳定率为69%（27/39），疾病进展率为8%（3/39）。83%的腹泻患者、46%的潮红患者、63%的喘息患者和75%的糙皮病患者的临床症状有显著减轻。总体临床益处率为63%。所有反应（临床益处和WHO反应）在随访期间（中位数6个月；范围2-12个月）持续存在。副作用为23%的3级或4级（NCI-CTC）淋巴细胞减少、3%的3级贫血和3%的2级肾功能不全。