title: Efficacy, toxicity and mode of interaction of combination radioimmunotherapy with 5-fluorouracil in colon cancer xenografts.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  The combination of two modalities would be feasible for the treatment of colon cancer, increasing antitumor effect with minor effect on toxicity.
authors.affiliation: Department of Nuclear Medicine, Kanazawa University School of Medicine, 13-1 Takaramachi, Kanazawa, Ishikawa 920-8640, Japan. kinuya@med.kanazawa-u.ac.jp
authors.forename: S
authors.initials: S
authors.lastname: Kinuya
authors.forename: K
authors.initials: K
authors.lastname: Yokoyama
authors.forename: H
authors.initials: H
authors.lastname: Tega
authors.forename: T
authors.initials: T
authors.lastname: Hiramatsu
authors.forename: S
authors.initials: S
authors.lastname: Konishi
authors.forename: N
authors.initials: N
authors.lastname: Watanabe
authors.forename: N
authors.initials: N
authors.lastname: Shuke
authors.forename: T
authors.initials: T
authors.lastname: Aburano
authors.forename: T
authors.initials: T
authors.lastname: Takayama
authors.forename: T
authors.initials: T
authors.lastname: Michigishi
authors.forename: N
authors.initials: N
authors.lastname: Tonami
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D001772:Blood Cell Count / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D003131:Combined Modality Therapy; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D005240:Feasibility Studies; D005260:Female; D005472:Fluorouracil / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D018796:Immunoconjugates / Q000009:adverse effects / Q000627:therapeutic use; D007457:Iodine Radioisotopes; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D016499:Radioimmunotherapy; D013997:Time Factors; D014018:Tissue Distribution; D016896:Treatment Outcome; D014407:Tumor Cells, Cultured
chemical_list: D000911:Antibodies, Monoclonal; D018796:Immunoconjugates; D007457:Iodine Radioisotopes; D005472:Fluorouracil