关键词: 结直肠肿瘤, 奥沙利铂, 老年人, 周围神经损伤, 抗肿瘤联合化疗方案

Abstract: Background　The addition of oxaliplatin to adjuvant chemotherapy for colorectal cancer has been shown to improve overall survival at the expense of increased toxicity.The incidence and severity of toxicity might be greater among older patients who might also derive less benefit from oxaliplatin.Objective　To evaluate the association between oxaliplatin-assisted chemotherapy and peripheral neuropathy in elderly patients with colorectal cancer.Methods　This study was a retrospective cohort study.A total of 38 085 patients aged 66 or above who underwent surgery for colorectal malignancies in the Department of Gastrointestinal Surgery of Hainan General Hospital and the Second Affiliated Hospital of Hainan Medical University from 2012 to 2015 were included in the study.Among 3 607 stage Ⅱ and Ⅲ patients receiving adjuvant chemotherapy，1 541 （42.72%） patients received oxaliplatin-assisted chemotherapy and 2 066 （57.28%） patients received fluorouracil chemotherapy alone.According to age，patients were divided into 66-69 years old group（n=987） and ≥70 years old group（n=2 620）.The clinical data were collected in the three-year follow up.As of 1 February 2018，the incidence of peripheral neuropathy，drug use rate of neuropathic pain and mortality rate were recorded.A multi-variable hazard modelling was constructed by the incidence of peripheral neuropathy and drug use rate of neuropathic pain.The cumulative incidence function was used to estimate the incidence of peripheral neuropathy，drug use rate of neuropathic pain，and mortality rate.Results　There were significant differences in gender，pathological stages，complication rate of dementia and stroke，Charlson's complications index （CCI） between two groups （P<0.05）.The proportion of pathological stageⅢ and colon cancer in patients aged 66-69 with oxaliplatin-assisted chemotherapy was higher than those without oxaliplatin-assisted chemotherapy，while the complication rate of diabetes mellitus and CCI were lower （P<0.05）.The proportion of male，pathological stageⅢ and colon cancer in patients aged 70 or above with oxaliplatin-assisted chemotherapy was higher than those without oxaliplatin-assisted chemotherapy，while the age，complication rate of dementia and CCI were lower （P<0.05）.Oxaliplatin-assisted chemotherapy was associated with an increased risk of peripheral neuropathy in all patients （P<0.05）.Oxaliplatin-assisted chemotherapy was not associated with an increased risk of peripheral neuropathy in patients aged 66-69 （P<0.05）.Oxaliplatin-assisted chemotherapy was associated with an increased risk of peripheral neuropathy in patients aged 70 or above（P<0.05）.Oxaliplatin-assisted chemotherapy was associated with increased use of gabapentin，tricyclic antidepressants and duloxetine in all patients （P<0.05）.Oxaliplatin-assisted chemotherapy was associated with increased use of tricyclic antidepressants in patients aged 66-69（P>0.05）.Oxaliplatin-assisted chemotherapy was associated with increased use of gabapentin and tricyclic antidepressants in patients aged 70 or above （P<0.05）.The incidence of peripheral neuropathy was 6.63% 〔95%CI（5.44%，7.97%）〕，the drug use rate of neuropathic pain was 15.43% 〔95%CI（13.61%，17.37%）〕 and the mortality rate was 14.72% 〔95%CI（13.04%，16.67%）〕 in patients receiving oxaliplatin-assisted chemotherapy for three years.Conclusion　Oxaliplatin-assisted chemotherapy in elderly patients with colorectal cancer can lead to peripheral neuropathy，especially in patients aged 70 and above who have a higher risk of peripheral neuropathy and drug use of neuropathic pain.Therefore，for adjuvant chemotherapy in elderly patients with colorectal cancer，it is necessary to fully consider the peripheral neuropathy.

Key words: Colorectal neoplasms, Oxaliplatin, Aged, Peripheral nerve injuries, Antineoplastic combined chemotherapy protocols