Combined radioimmunotherapy and chemotherapy of human colon carcinoma grafted in nude mice, advantages and limitations.
In order to determine if 5-fluorouracil (5FU) could potentiate the effect of radioimmunotherapy (RIT), nude mice bearing subcutaneous human colon carcinoma xenografts were treated by 1 or 2 intravenous injection(s) of subtherapeutic doses of 131I labeled F(ab')2 from anti-carcinoembryonic antigen monoclonal antibodies combined with 5 daily intraperitoneal injections of 5FU. Control mice received either 131I F(ab')2 alone, 5FU alone or no treatment. RIT alone induced significant tumor regression, while 5FU alone gave only minimal tumor growth inhibition. The combined treatment group also resulted in long-term tumor regression with tumors remaining significantly smaller than in the RIT alone group. There was however, no significant difference in tumor recurrence time between the groups treated with RIT alone or with RIT + 5FU. Myelotoxicity, the major side effect of RIT, detected by the decrease of peripheral white blood cells (WBC), was shown to be almost identical between the groups receiving only RIT or only 5FU. Surprisingly, there was no cumulative bone marrow toxicity in animals which received 5FU before RIT. Furthermore, in the latter group, the WBC levels after RIT were significantly higher than in the control group receiving only RIT. Taken together, the results demonstrate the higher therapeutic efficiency of RIT as compared to 5FU in this model. They do not show, however, that the combination of the two forms of treatment can induce longer tumor remission. Interestingly, the WBC results suggest that 5FU given before RIT can have a radioprotective effect on bone marrow, possibly by selecting radioresistant bone marrow stem cells.
Chalandon
Y
Y
Institute of Biochemistry, University of Lausanne, Epalinges, Switzerland.
Mach
J P
JP
Pèlegrin
A
A
Folli
S
S
Buchegger
F
F
D000818:Animals; D003110:Colonic Neoplasms / Q000532:radiotherapy*; D003131:Combined Modality Therapy; D004334:Drug Administration Schedule; D005472:Fluorouracil / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000627:therapeutic use*; D007457:Iodine Radioisotopes / Q000627:therapeutic use*; D007958:Leukocyte Count / Q000187:drug effects; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D016499:Radioimmunotherapy / Q000009:adverse effects / Q000379:methods*; D012074:Remission Induction; D015431:Weight Loss
D007140:Immunoglobulin Fab Fragments; D007457:Iodine Radioisotopes; D005472:Fluorouracil