Potential Factors in Oxaliplatin-Induced Peripheral Neuropathy in Patients With Stage III Colon Cancer

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In an analysis from the phase III CALGB (Alliance)/SWOG 80702 trial of adjuvant FOLFOX (fluorouracil, leucovorin, and oxaliplatin) for patients with stage III colon cancer reported in the Journal of Clinical Oncology, Lee et al found that longer duration of oxaliplatin treatment was associated with higher-grade oxaliplatin-induced peripheral neuropathy (OIPN), and that less physical activity, higher body mass index (BMI), and the presence of diabetes may be associated with worse OIPN independent of oxaliplatin duration.

Study Details

The analysis included 2,450 patients who were randomly assigned to 6 vs 12 cycles of FOLFOX with or without 3 years of celecoxib. OIPN was reported by patients using the Common Terminology Criteria for Adverse Events (CTCAE; graded as 0 [none] to 4) during and following completion of chemotherapy and the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity-13 (FACT/GOG-NTX-13; impact of symptoms during preceding week, graded as 0 [none] to 4) 15 to 17 months after random assignment.

Key Findings

Compared with patients receiving 6 cycles of oxaliplatin, those receiving 12 were more likely to have higher-grade CTCAE-reported neuropathy during (adjusted odds ratio [aOR] = 4.4, P < .001) and after completion (aOR = 3.76, P < .001) of oxaliplatin treatment, and were also more likely to have worse FACT/GOG-NTX-13–reported neuropathy severity (P < .001). Patients receiving 12 cycles with any degree of CTCAE-reported neuropathy had longer times to neuropathy resolution. Receipt of celecoxib was not associated with any significant effect on reported OIPN.

Among patient factors, potential associations with OIPN severity were observed according to exercise level, BMI, and presence of diabetes, but not with vitamin B6 intake. Patients exercising for ≥ 9 vs < 9 MET-hours per week after treatment had significantly lower FACT/GOG-NTX-13–reported neuropathy severity (P = .003). No significant associations between exercise and CTCAE-reported neuropathy grade were observed during treatment or follow-up.

Patients with a baseline BMI of ≥ 25 vs < 25 kg/m2 had greater risk of higher-grade CTCAE-reported neuropathy during (aOR = 1.18, P = .05) and following completion (aOR = 1.23, P = .04) of oxaliplatin treatment. No significant differences in FACT/GOG-NTX-13–reported neuropathy severity were observed according to BMI.

Patients with vs without diabetes were significantly more likely to have worse FACT/GOG-NTX-13–reported neuropathy (P = .002). No significant differences in CTCAE-reported neuropathy grade during or after completion of oxaliplatin were observed according to presence or absence of diabetes.

No significant interactions were observed between oxaliplatin treatment duration and effects of exercise, BMI, and diabetes on neuropathy severity.

The investigators concluded, “Lower physical activity, higher BMI, diabetes, and longer planned treatment duration, but not celecoxib use or vitamin B6 intake, may be associated with significantly increased OIPN severity.”

Jeffrey A. Meyerhardt, MD, MPH, of Dana-Farber Cancer Institute, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The study was supported by grants from the National Cancer Institute and others. For full disclosures of the study authors, visit

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