Abstract
OBJECTIVE: Chronic chemotherapy-induced peripheral neuropathy (CIPN) is a long-lasting side-effect of oxaliplatin. Vitamin B6 might play a role in the pathogenesis of CIPN. Therefore, we investigated associations between plasma vitamin B6 markers and the occurrence and severity of chronic CIPN in patients with non-metastatic colorectal cancer (CRC). METHODS AND ANALYSIS: 242 patients with CRC receiving oxaliplatin-based chemotherapy were included. Blood samples were collected at diagnosis (ie, before chemotherapy), and 6 and 12 months after diagnosis (ie, during and after chemotherapy, respectively). Pyridoxal 5'-phosphate (PLP), pyridoxal (PL) and xanthurenic acid:3-hydroxykynurenine (XA:HK) ratio were measured as vitamin B6 markers using liquid chromatography tandem mass spectrometry. Chronic CIPN was assessed 12 months after diagnosis using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-CIPN twenty-item scale questionnaire. Prevalence ratios (PRs) and restricted cubic splines (RCSs) were used to assess associations with chronic CIPN occurrence, and linear regressions were used to assess associations with chronic CIPN severity. Analyses were adjusted for age, sex, smoking, alcohol consumption, diabetes and timing of chemotherapy (neoadjuvant/adjuvant/both). RESULTS: Chronic CIPN was found in 80% (n=194) of patients. Higher PLP levels and XA:HK ratios during chemotherapy were associated with lower occurrence of chronic CIPN (PR(perdoubling) 0.75, 95% CI 0.62 to 0.91 and P(RCS)<0.05, respectively) and lower chronic CIPN severity (β(perdoubling) -4.54, 95% CI -7.12 to -1.96 and β(perdoubling) -6.30, 95% CI -9.53 to -3.07, respectively). No associations between PL levels and chronic CIPN were observed. CONCLUSION: Within this population, merely having PLP levels within the normal range, higher vitamin B6 status during chemotherapy was associated with lower occurrence and severity of chronic CIPN. Future research is warranted to investigate causality and the optimal vitamin B6 status during chemotherapy.