Efficacy, toxicity and mode of interaction of combination radioimmunotherapy with 5-fluorouracil in colon cancer xenografts.
J Cancer Res Clin Oncol, 1999/11;125(11):630-6.
Kinuya S[1], Yokoyama K, Tega H, Hiramatsu T, Konishi S, Watanabe N, Shuke N, Aburano T, Takayama T, Michigishi T, Tonami N
Affiliations
PMID: 10541970
Impact factor: 4.322
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.
MeSH terms
Animals; Antibodies, Monoclonal; Blood Cell Count; Colonic Neoplasms; Combined Modality Therapy; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; Feasibility Studies; Female; Fluorouracil; Humans; Immunoconjugates; Iodine Radioisotopes; Mice; Mice, Nude; Neoplasm Transplantation; Radioimmunotherapy; Time Factors; Tissue Distribution; Treatment Outcome; Tumor Cells, Cultured
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