A phase I study of vitamin E, 5-fluorouracil and leucovorin for advanced malignancies

Six patients with incurable malignancies were originally treated with vitamin E, 3200 IU/day for fourteen days, followed by the same dose of vitamin E daily plus LCV (20 mg/m² iv bolus daily × 5) with 5FU (425 mg/m² iv bolus immediately following LCV). The same schedule of LCV and 5FU was repeated 4 weeks later, then every 5 weeks indefinitely. When 3 of the first 6 had grade 3/4 toxicity, six more patients were treated on the identical drugs and schedule. Seven of twelve total patients had one or more grade 3/4 toxicities. Neutropenia, abdominal pain, and diarrhea were most common. No patient had a documented response, though seven patients did have stable disease. Though the combination of vitamin E and chemotherapy was toxic, this trial demonstrated maximal therapeutic doses of vitamin E can be combined with standard 5FU and LCV, without significantly increasing the side effects of the chemotherapy itself.