联合放免治疗和贝伐单抗治疗在甲状腺髓样癌小鼠模型中的毒性和疗效。

Toxicity and efficacy of combined radioimmunotherapy and bevacizumab in a mouse model of medullary thyroid carcinoma.

机构信息

Nuclear Oncology Department, Cancer Research Center, INSERM U892, Université de Nantes, Nantes, France.

出版信息

Cancer. 2010 Feb 15;116(4 Suppl):1053-8. doi: 10.1002/cncr.24792.

DOI:10.1002/cncr.24792

PMID:20127950

Abstract

BACKGROUND

Significant antitumor effects were previously observed with radioimmunotherapy (RIT) using an anti-carcinoembryonic antigen (CEA) monoclonal antibody (F6) labeled with iodine-131 in medullary thyroid cancer (MTC)-bearing nude mice. Nevertheless, no complete response was achieved. Because angiogenesis is critical for tumor growth, bevacizumab is used to treat solid tumor in clinical practice. The present pilot study evaluated toxicity and efficacy of RIT combined with bevacizumab in mice subcutaneously grafted with TT MTC cells.

METHODS

Groups of 4-6 nude mice were treated with 5 microg/g bevacizumab twice weekly during 4 weeks and/or 100 MBq of (131)I-F6. For combined therapy, bevacizumab was given at Day 0 followed by (131)I-F6 at Day 30. The control group received no treatment. Animal weight, hematological toxicity, tumor volume, and serum calcitonin were monitored for 2 or 4 months.

RESULTS

Bevacizumab alone induced no cytopenia and no significant weight loss. A weight loss of 12 +/- 1% and 15 +/- 2% was observed in mice treated by RIT alone or bevacizumab + RIT, respectively. RIT alone and combined treatment induced leukopenia and anemia. RIT alone and RIT plus bevacizumab induced tumor responses with minimum relative tumor volume of 0.38 +/- 0.24 and 0.15 +/- 0.07%, respectively, and time to progression of 35 +/- 5 and 56 +/- 11 days, respectively.

CONCLUSIONS

Pretreatment with bevacizumab improved RIT efficacy, with similar toxicity as compared as RIT alone.

摘要

背景

先前在携带髓样甲状腺癌（MTC）的裸鼠中使用碘-131 标记的抗癌胚抗原（CEA）单克隆抗体（F6）进行放射免疫治疗（RIT）时观察到了显著的抗肿瘤作用。然而，没有达到完全缓解。由于血管生成对于肿瘤生长至关重要，贝伐单抗在临床上用于治疗实体瘤。本初步研究评估了贝伐单抗联合 RIT 治疗皮下移植 TT MTC 细胞的裸鼠的毒性和疗效。

方法

4-6 只裸鼠一组，在 4 周内每周两次接受 5 μg/g 的贝伐单抗治疗，共 4 周，或接受 100MBq 的（131）I-F6。对于联合治疗，贝伐单抗在第 0 天给药，然后在第 30 天给予（131）I-F6。对照组未接受治疗。监测动物体重、血液学毒性、肿瘤体积和血清降钙素 2 或 4 个月。

结果

贝伐单抗单独使用不会引起血细胞减少症，也不会导致明显的体重减轻。单独接受 RIT 治疗或贝伐单抗+RIT 治疗的小鼠体重分别减轻 12%±1%和 15%±2%。单独 RIT 和联合治疗引起白细胞减少和贫血。单独 RIT 和 RIT 加贝伐单抗诱导肿瘤反应，最小相对肿瘤体积分别为 0.38±0.24 和 0.15±0.07%，进展时间分别为 35±5 和 56±11 天。