Clinical trial of pyridoxine to reduce vincristine neurotoxicity.

In a murine model system, pyridoxine has demonstrated protective properties during administration of lethal doses of vincristine (VCR). Subsequently, pyridoxine has been evaluated in patients receiving VCR during an adjuvant chemotherapy program for stage II carcinoma of the breast. The toxicities, cumulative VCR dosage, and percentage of ideal dosage observed in 24 patients receiving pyridoxine have been compared to those observed in 88 patients who previously received VCR without pyridoxine in the same chemotherapy program. All patients ideally were to receive VCR 1.0 mg/m2 weekly for 6-weeks with dose modification for neurotoxicity. Treatment patients received pyridoxine 1.5 grams p.o. daily in three divided doses during the 6-week course. The degree of neurotoxic manifestations of VCR was similar in the treatment and comparison patients. Absent to mild neurotoxicity was observed in approximately 70% of patients in both groups; moderate or greater neurotoxicity occurred in about 30% of patients in both groups. Full dosage (6.0 mg/m2) was attained in 8 (33%) treatment patients and 18 (24%) comparison patients (p = 0.28). The mean percentage of ideal dosage of VCR was 84.6 +/- 10.8 in patients receiving pyridoxine and 81.9 +/- 21.6 in those given only VCR (p = 0.59). Gastrointestinal and hematologic toxicities were similar in both groups. Pyridoxine in this dose and schedule afforded no protection from the neurotoxic side effects of VCR.