Neuroprotective Effect of Vitamin B6 and Vitamin B12 against Vincristine- Induced Peripheral Neuropathy: A Randomized, Double- Blind, Placebo Controlled, Multicenter Trial

Abstract

Background: Vincristine leads to development of debilitating neuropathy in 40-45% patients with resultant compromised efficacy of chemotherapy, suboptimal treatment and worse prognostic outcome. Vitamin B6 and vitamin B12 improves non- oncological neuropathies. Therefore, this study investigated vitamin B6 and vitamin B12 to prevent vincristine- induced peripheral neuropathy (VIPN) by reducing incidence, absolute risk, relative risk, severity as well as delaying the onset. Methods: Patients with ALL undergoing induction phase were randomly assigned into intervention or placebo arm in a double- blind manner. Vitamin B6 (25 mg Pyridoxine) two tablets were given three times daily for 5 weeks. Vitamin B12 (500 μg/ml Methyl cobalamin) was administered intravenously on day 1, 3 and 5 of every week for 5 weeks during induction period. Placebo arm received oral and intravenous placebo for same duration. Patients were evaluated on the outset of every week by FACT/GOG-NTX questionnaire. Severity was assessed per NCI-CTCAE grading scale. Results: 102 patients were enrolled. Among them 81 completed the study, where 42 received vitamin B6 and B12 and 39 received placebo. There was significant difference in incidence of neuropathy between arms (26.19% intervention arm, 56.41% placebo; P-0.01). Relative risk of neuropathy was significantly (RR-0.46) lower in intervention arm. Besides, absolute risk reduction (ARR) was 30% and relative risk reduction (RRR) was 54%. NNT was 3.33. Significant trend was observed in difference of severity of VIPN between groups (P-0.03). No significant difference observed in between arms for time to onset of neuropathy. Conclusion: Vitamin B6 and vitamin B12 significantly reduced the incidence, relative risk and severity of VIPN. NNT was encouraging too. Henceforth, the status of vitamin B6 and vitamin B12 as neuroprotective agent against VIPN can be recommended as a promising one.