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

Our purpose was to determine whether the administration of anti-oxidant vit amins could reduce dose-limiting toxicity from radio-immunotherapy (RAIT) a nd thereby allow higher escalation of RAIT doses. Lipophilic vitamins A and E were administered i.p. and hydrophilic vitamin C was administered i.m. f or 14 days (3 days pre-RAIT through 11 days post-BAIT) alone or with bone m arrow transplantation (BMT) to either BALB/c mice for toxicity studies or t o nude mice bearing s.c. GW-39 human colonic cancer xenografts for therapy studies. The maximal tolerated dose (MTD) of RAIT (131I-MN-14 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 tu mor 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 m yelosuppression, As early as day 7 after RAIT, vitamins increased WBC count s following both a 400 mu Ci and a 500 mu Ci dose. On day 14 after the 400 mu Ci dose of BAIT (day 7 post-BMT), the additive effect of BMT and vitamin could be detected, Tumor growth was not adversely affected by vitamin admi nistration. Int. J. Cancer 86:276-280, 2000, (C) 2000 Wiley-Liss. Inc.