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

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) ¹³¹I-A7, an IgG1 against 45-kDa glycoprotein, and 5-FU at a dose of 30 mg kg⁻¹day⁻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.