Anti-oxidant vitamins reduce normal tissue toxicity induced by radio-immunotherapy

Our purpose was to determine whether the administration of anti-oxidant vitamins could reduce dose-limiting toxicity from radio-immunotherapy (RAIT) and thereby allow higher escalation of RAIT doses. Lipophilic vitamins A and E were administered i.p. and hydrophilic vitamin C was administered i.m. for 14 days (3 days pre-RAIT through 11 days post-RAIT) alone or with bone marrow transplantation (BMT) to either BALB/c mice for toxicity studies or to nude mice bearing s.c. GW-39 human colonic cancer xenografts for therapy studies. The maximal tolerated dose (MTD) of RAIT ((131)I-MN14 anti-CEA IgG) that results in no lethality was determined for mice that did not receive vitamins or BMT and those that did receive one or both interventions. Body weight, peripheral white blood cell (pWBC) and platelet (PLT) counts and tumor growth were also measured. Administration of vitamins (equivalent of 3.5 IU/day vitamin A, 0.107 IU/day vitamin E and 4.0 mg/day ascorbic acid) to mice along with BMT increased the MTD by 42% and reduced body weight loss associated with RAIT. Vitamins also reduced the magnitude of RAIT-induced myelosuppression. As early as day 7 after RAIT, vitamins increased WBC counts following both a 400 microCi and a 500 microCi dose. On day 14 after the 400 microCi dose of RAIT (day 7 post-BMT), the additive effect of BMT and vitamin could be detected. Tumor growth was not adversely affected by vitamin administration.