Michael J Raphael1, Hadas D Fischer2, Kinwah Fung2, Peter C Austin3, Geoffrey M Anderson3, Christopher M Booth4, Simron Singh5. 1. Division of Medical Oncology, Department of Medicine, University of Toronto, Toronto, ON, Canada. 2. Institute for Clinical Evaluative Sciences, Toronto, ON, Canada. 3. Institute for Clinical Evaluative Sciences, Toronto, ON, Canada; Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, ON, Canada. 4. Institute for Clinical Evaluative Sciences, Toronto, ON, Canada; Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, ON, Canada; Division of Cancer Care and Epidemiology, Queen's University Cancer Research Institute, Kingston, ON, Canada. 5. Division of Medical Oncology, Department of Medicine, University of Toronto, Toronto, ON, Canada; Institute for Clinical Evaluative Sciences, Toronto, ON, Canada. Electronic address: simron.singh@sunnybrook.ca.
Abstract
BACKGROUND: The addition of oxaliplatin to adjuvant treatment regimens 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. We evaluated the association between adjuvant oxaliplatin-based chemotherapy and neurotoxicity outcomes in an elderly cohort of patients. PATIENTS AND METHODS: A population-based cohort of patients aged > 65 years with stage II and III colorectal cancer treated with adjuvant therapy in Ontario, Canada was identified using the Ontario Cancer Registry. Cause-specific hazard models were used to estimate the effect of oxaliplatin exposure on the cause-specific hazard ratio (CHR) of peripheral neuropathy after accounting for the competing risk of death. RESULTS: We identified 3607 patients aged > 65 years with stage II and III colorectal cancer. Of these patients, 1541 (43%) had been treated with an oxaliplatin-based regimen. Compared with subjects receiving non-oxaliplatin-based regimens, patients aged ≥ 70 years at the time of cancer diagnosis who are subsequently treated with oxaliplatin were more likely to develop peripheral neuropathy (CHR, 2.3; 95% confidence interval [CI], 1.53-3.35; P < .0001). This association was not significant in patients aged 66 to 69 years (CHR, 0.93; 95% CI, 0.50-1.72; P = .812). Formal interaction testing confirmed that the effect of oxaliplatin on neuropathy was more pronounced in patients aged ≥ 70 years compared with patients aged 66 to 69 years (P = .03). CONCLUSION: Colorectal cancer patients aged ≥ 70 years at the time of cancer diagnosis who are subsequently treated with oxaliplatin have a significant risk of developing peripheral neuropathy. This should be considered in clinical decision making, especially because of the limited data supporting an oxaliplatin benefit in this age group.
BACKGROUND: The addition of oxaliplatin to adjuvant treatment regimens 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. We evaluated the association between adjuvant oxaliplatin-based chemotherapy and neurotoxicity outcomes in an elderly cohort of patients. PATIENTS AND METHODS: A population-based cohort of patients aged > 65 years with stage II and III colorectal cancer treated with adjuvant therapy in Ontario, Canada was identified using the Ontario Cancer Registry. Cause-specific hazard models were used to estimate the effect of oxaliplatin exposure on the cause-specific hazard ratio (CHR) of peripheral neuropathy after accounting for the competing risk of death. RESULTS: We identified 3607 patients aged > 65 years with stage II and III colorectal cancer. Of these patients, 1541 (43%) had been treated with an oxaliplatin-based regimen. Compared with subjects receiving non-oxaliplatin-based regimens, patients aged ≥ 70 years at the time of cancer diagnosis who are subsequently treated with oxaliplatin were more likely to develop peripheral neuropathy (CHR, 2.3; 95% confidence interval [CI], 1.53-3.35; P < .0001). This association was not significant in patients aged 66 to 69 years (CHR, 0.93; 95% CI, 0.50-1.72; P = .812). Formal interaction testing confirmed that the effect of oxaliplatin on neuropathy was more pronounced in patients aged ≥ 70 years compared with patients aged 66 to 69 years (P = .03). CONCLUSION:Colorectal cancerpatients aged ≥ 70 years at the time of cancer diagnosis who are subsequently treated with oxaliplatin have a significant risk of developing peripheral neuropathy. This should be considered in clinical decision making, especially because of the limited data supporting an oxaliplatin benefit in this age group.
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