联合放射免疫疗法与5-氟尿嘧啶治疗结肠癌异种移植瘤的疗效、毒性及相互作用模式

Efficacy, toxicity and mode of interaction of combination radioimmunotherapy with 5-fluorouracil in colon cancer xenografts.

作者信息

Kinuya S, Yokoyama K, Tega H, Hiramatsu T, Konishi S, Watanabe N, Shuke N, Aburano T, Takayama T, Michigishi T, Tonami N

机构信息

Department of Nuclear Medicine, Kanazawa University School of Medicine, 13-1 Takaramachi, Kanazawa, Ishikawa 920-8640, Japan.

出版信息

J Cancer Res Clin Oncol. 1999 Nov;125(11):630-6. doi: 10.1007/s004320050326.

DOI:10.1007/s004320050326

PMID:10541970

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12169123/

Abstract

PURPOSE

The feasibility of radioimmunotherapy (RAIT) combined with 5-fluorouracil (5-FU) was examined in colon cancer xenografts. The mode of interaction of the two treatments was also investigated.

METHODS

Mice bearing human colon cancer were treated with a combination of 4.63 MBq (L-RAIT) or 9.25 MBq (H-RAIT) (131)I-A7, an IgG1 against 45-kDa glycoprotein, and 5-FU at a dose of 30 mg kg(-1)day(-1) for 5 days. Myelotoxicity was monitored by blood cell counts and intestinal toxicity was assessed by the dosimetry. The results were compared with those of a single-modality therapy.

RESULTS

The combination of 5-FU with H-RAIT enhanced the antitumor effect, improving the tumor quadrupling time from 25.3 +/- 9.59 days to 31.3 +/- 8.32 days (P < 0.05) and inducing tumor regression in 7 out of 10 mice, compared to 3 out of 9 mice treated with H-RAIT alone. The efficacy of L-RAIT was also improved by the combination. Analysis of the dose/response relationship showed an additive interaction of the two modalities. The combination of 5-FU with RAIT induced slightly more severe myelotoxicity than a single-modality treatment, but blood cell counts recovered similarly. Dose estimation suggested that RAIT does not increase the intestinal toxicity of 5-FU.

CONCLUSION

The combination of two modalities would be feasible for the treatment of colon cancer, increasing antitumor effect with minor effect on toxicity.

摘要

目的

在结肠癌异种移植模型中研究放射免疫疗法（RAIT）联合5-氟尿嘧啶（5-FU）的可行性。同时也研究了两种治疗方法的相互作用模式。

方法

用人结肠癌荷瘤小鼠，给予4.63 MBq（低剂量RAIT，L-RAIT）或9.25 MBq（高剂量RAIT，H-RAIT）的（131）I-A7（一种针对45 kDa糖蛋白的IgG1）联合5-FU，剂量为30 mg kg(-1)天(-1)，共5天。通过血细胞计数监测骨髓毒性，通过剂量测定评估肠道毒性。将结果与单一疗法的结果进行比较。

结果

5-FU与H-RAIT联合使用增强了抗肿瘤效果，使肿瘤四倍增长时间从25.3±9.59天延长至31.3±8.32天（P<0.05），10只小鼠中有7只出现肿瘤消退，而单独接受H-RAIT治疗的9只小鼠中只有3只出现肿瘤消退。联合使用也提高了L-RAIT的疗效。剂量/反应关系分析显示两种治疗方法具有相加作用。5-FU与RAIT联合使用引起的骨髓毒性比单一疗法略严重，但血细胞计数恢复情况相似。剂量估计表明RAIT不会增加5-FU的肠道毒性。