Background: There are few background data on the impact of clinical factors on neurotoxicity and prognosis in patients treated with adjuvant capecitabine and oxaliplatin (CAPOX) chemotherapy. Methods: 102 stage II high-risk and stage III colorectal cancer patients were treated for 6 months with adjuvant CAPOX, then they were followed up. Associations between clinical variables, metabolic syndrome components, smoking and neurotoxicity were evaluated by the χ2 test. The Kaplan-Meier product limit method was applied to graph disease-free survival (DFS). Univariate analysis was done with the log-rank test. Cox's proportional hazards regression was used to analyze the effect of several risk factors on DFS. Results: Significant associations were found between diabetes (p < 0.001), BMI (p = 0.01) and the occurrence of chronic neurotoxicity. After a median follow-up of 46 months, 14 patients (13.7%) had suffered recurrence. An analysis of the prognostic factors for DFS showed that prognosis is unfavorable for patients with high lymph-nodal involvement (HR: 5.23, p = 0.0007), diabetes (HR: 4.86; p = 0.03) and a BMI ≥25 (HR: 3.69, p = 0.002). Discussion: Common mediators in diabetes and obesity could be involved in peripheral neuropathy and in stimulating micro-metastases. Further studies are necessary to explain this interesting connection between diabetes, obesity and colon cancer.

Jemal A, Siegel R, Xu J, Ward E: Cancer statistics, 2010. CA Cancer J Clin 2010;60:277-300.
Schmoll HJ, Twelves C, Sun W, et al: Effect of adjuvant capecitabine or fluorouracil, with or without oxaliplatin, on survival outcomes in stage III colon cancer and the effect of oxaliplatin on post-relapse survival: a pooled analysis of individual patient data from four randomised controlled trials. Lancet Oncol 2014;15:1481-1492.
Dienstmann R, Salazar R, Tabernero J: Personalizing colon cancer adjuvant therapy: selecting optimal treatments for individual patients. J Clin Oncol 2015;33:1787-1796.
Avan A, Postma TJ, Ceresa C, et al: Platinum-induced neurotoxicity and preventive strategies: past, present, and future. Oncologist 2015;20:411-432.
Zedan AH, Hansen TF, Fex Svenningsen A, Vilholm OJ: Oxaliplatin-induced neuropathy in colorectal cancer: many questions with few answers. Clin Colorectal Cancer 2014;13:73-80.
Smith CJ, Ryckman KK: Epigenetic and developmental influences on the risk of obesity, diabetes, and metabolic syndrome. Diabetes Metab Syndr Obes 2015;8:295-302.
Esposito K, Chiodini P, Capuano A, et al: Colorectal cancer association with metabolic syndrome and its components: a systematic review with meta-analysis. Endocrine 2013;44:634-647.
Shen Z, Ye Y, Bin L, et al: Metabolic syndrome is an important factor for the evolution of prognosis of colorectal cancer: survival, recurrence, and liver metastasis. Am J Surg 2010;200:59-63.
Noto H, Goto A, Tsujimoto T, et al: Latest insights into the risk of cancer in diabetes. J Diabetes Investig 2013;4:225-232.
Maruthur NM, Bolen S, Gudzune K, et al: Body mass index and colon cancer screening: a systematic review and meta-analysis. Cancer Epidemiol Biomarkers Prev 2012;21:737-746.
Altaf R, Lund Brixen A, Kristensen B, Nielsen SE: Incidence of cold-induced peripheral neuropathy and dose modification of adjuvant oxaliplatin-based chemotherapy for patients with colorectal cancer. Oncology 2014;87:167-172.
Park SB, Goldstein D, Lin CS, et al: Acute abnormalities of sensory nerve function associated with oxaliplatin-induced neurotoxicity. J Clin Oncol 2009;27:1243-1249.
Lecomte T, Landi B, Beaune P, et al: Glutathione S-transferase P1 polymorphism (Il1105Val) predicts cumulative neuropathy in patients receiving oxaliplatin-based chemotherapy. Clin Cancer Res 2006;12:3050-3056.
Ruzzo A, Graziano F, Loupakis F, et al: Pharmacogenetic profiling in patients with advanced colorectal cancer treated with first-line FOLFOX-4 chemotherapy. J Clin Oncol 2007;25:1247-1254.
Velasco R, Bruna J, Briani C, et al: Early predictors of oxaliplatin-induced cumulative neuropathy in colorectal cancer patients. J Neurol Neurosurg Psychiatry 2014;85:392-398.
Argyriou AA, Cavaletti G, Briani C, et al: Clinical pattern and associations of oxaliplatin acute neurotoxicity: a prospective study in 170 patients with colorectal cancer. Cancer 2013;119:438-444.
de Gramont A, Figer A, Seymour M, et al: Leucovorin and fluorouracil with or without oxaliplatin as first-line treatment in advanced colorectal cancer. J Clin Oncol 2000;18:2938-2947.
Ramanathan RK, Rothenberg ML, de Gramont A, et al: Incidence and evaluation of oxaliplatin-induced peripheral sensory neuropathy in diabetic patients with colorectal cancer: a pooled analysis of three phase III studies. Ann Oncol 2010;21:754-758.
Uwah AN, Ackler J, Leighton JC Jr, et al: The effect of diabetes on oxaliplatin-induced peripheral neuropathy. Clin Colorectal Cancer 2012;11:275-279.
Cascinu S, Catalano V, Cordella L, et al: Neuroprotective effect of reduced glutathione on oxaliplatin-based chemotherapy in advanced colorectal cancer: a randomized, double-blind, placebo-controlled trial. J Clin Oncol 2002;20:3478-3483.
Knijn N, Tol J, Koopman M, et al: The effect of prophylactic calcium and magnesium infusions on the incidence of neurotoxicity and clinical outcome of oxaliplatin-based systemic treatment in advanced colorectal cancer patients. Eur J Cancer 2011;47:369-374.
Aathira R, Jain V: Advances in management of type 1 diabetes mellitus. World J Diabetes 2014;5:689-696.
George AM, Jacob AG, Fogelfeld L: Lean diabetes mellitus: an emerging entity in the era of obesity. World J Diabetes 2015;6:613-620.
Chen KH, Shao YY, Lin ZZ, et al: Type 2 diabetes mellitus is associated with increased mortality in Chinese patients receiving curative surgery for colon cancer. Oncologist 2014;19:951-958.
Mills KT, Bellows CF, Hoffman AE, et al: Diabetes mellitus and colorectal cancer prognosis: a meta-analysis. Dis Colon Rectum 2013;56:1304-1319.
Chang CC, Wu MJ, Yang JY, et al: Leptin-STAT3-G9a signaling promotes obesity-mediated breast cancer progression. Cancer Res 2015;75:2375-2386.
Joshi RK, Kim WJ, Lee SA: Association between obesity-related adipokines and colorectal cancer: a case-control study and meta-analysis. World J Gastroenterol 2014;20:7941-7949.
Husain K, Hernandez W, Ansari RA, Ferder L: Inflammation, oxidative stress and renin angiotensin system in atherosclerosis. World J Biol Chem 2015;6:209-217.
Orgel E, Mittelman SD: The links between insulin resistance, diabetes, and cancer. Curr Diab Rep 2013;13:213-222.
Renehan AG, Zwahlen M, Minder C, et al: Insulin-like growth factor (IGF)-I, IGF binding protein-3, and cancer risk: systematic review and meta-regression analysis. Lancet 2004;363:1346-1353.
Califano D, Pignata S, Losito NS, et al: High HMGA2 expression and high body mass index negatively affect the prognosis of patients with ovarian cancer. J Cell Physiol 2014;229:53-59.
Vucenik I, Stains JP: Obesity and cancer risk: evidence, mechanisms, and recommendations. Ann NY Acad Sci 2012;1271:37-43.
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