Neurotoxicity outcomes in a population-based cohort of elderly patients treated with adjuvant oxaliplatin for colorectal cancer

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. Toxicity may be higher among older patients who may also derive less benefit from oxaliplatin. We aimed to evaluate 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 > 65 years old 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 (CHR) of peripheral neuropathy after accounting for the competing risk of death.

Results — We identified 3,607 patients >65 years old with Stage II and III colorectal cancer, of whom 1,541 (43%) were treated with an oxaliplatin-based regimen. Compared to subjects receiving non-oxaliplatin based regimens, patients ≥ 70 years old treated with oxaliplatin were more likely to be diagnosed with peripheral neuropathy (CHR, 2.3 [95% CI, 1.53-3.35; p < 0.0001]); this association was not significant in patients aged 66-69 (CHR, 0.93 [95% CI, 0.50-1.72; p=0.812). Formal interaction testing confirmed the effect of oxaliplatin on neuropathy was more pronounced in patients ≥ 70 years old compared to patients 66-69 (p=0.03).

Conclusions — Colorectal cancer patients ≥ 70 years old treated with oxaliplatin have a significant risk of developing peripheral neuropathy. This should be taken into consideration in clinical decision making in the context of limited data supporting oxaliplatin benefit in this age group.