Effects of newly developed chemotherapy regimens, comorbidities, chemotherapy-related toxicities on the changing patterns of the leading causes of death in elderly patients with colorectal cancer

Background: Abundant evidences have shown that newly developed chemotherapy regimens improved 5-year survival rate of colorectal cancer (CRC) patients over the past two decades. However, their impact on risk of death from leading causes among elderly patients is still poorly understood. Patients and methods: A retrospective cohort study of 69 718 elderly CRC patients with their first primary tumors in 1992-2009, identified from the 12 areas of Surveillance, Epidemiology, and End Results-Medicare linked database with their Medicare claims up to 2010. Multivariate Cox regression models were used to assess the effect of newly developed chemotherapy regimens, comorbidities, and chemotherapy related toxicities on cause-specific death and their temporal patterns among elderly CRC patients. Results: The leading causes of death among CRC patients were CRC, circulation disorders, and secondary cancers, which accounted for 51.4%, 25%, and 4.6% of all-cause death, respectively. Patients diagnosed in more recent diagnostic time periods were significantly less likely to die of CRC [period 2: 5-year hazard ratio = 0.94, 95% confidence interval (CI) 0.90-0.97; period 3: 0.86, 0.83-0.90], circulation disorders (period 2: 0.94, 0.88-1.00; period 3: 0.80, 0.75-0.87), and more likely to die of secondary cancer (period 3: 1.42, 1.20-1.68) compared with those diagnosed in period 1. Charlson comorbidities index and the selected pre-existing comorbidities were significantly associated with increased 5-year risk of death from all three leading causes. Both hematological and gastric toxicity were associated with reduced risk of death from CRC and circulation disorders. The association between diagnostic time period and risk reduction in death from CRC depended on chemotherapy treatment (P < 0.0001). Subgroup analyses showed that the chemotherapy-dependent significant risk reduction was seen in patients with stage II-III CRC, patients without comorbidities, and patients without toxicities (P < 0.0001 for all). Conclusion: The newly developed chemotherapy regimens were associated with the decreased risk of mortality from CRC.