Older CRC Patients at Increased Risk for New-Onset Cardiotoxicity

Kelly M. Kenzik, PhD

Older patients with colorectal cancer (CRC) are more likely to develop cardiovascular disease (CVD) and congestive heart failure (CHF), according to results from an analysis of the SEER database. Researchers reported that both diabetes and hypertension interact with chemotherapy to increase the cardiovascular risk for these patients.

The median age at diagnosis was 78 years (range, 66-106) with a median follow-up of 8 years since diagnosis. At 10 years, the cumulative incidence of new-onset CVD was 57.4% in the study population and the cumulative incidence of new-onset CHF was 54.5%. Those rates were 22% and 18%, respectively, in the age-matched control group (P <.001).

Time to CHF diagnosis was 58% shorter in patients with CRC compared with noncancer controls (HR, 4.19; 95% CI, 14.06-4.33). Time to developing CVD was 57.4% shorter in CRC patients, which translates to a 3.07-fold increased risk for CVD (95% CI, 2.98-3.16).

“Older survivors of colorectal cancer carry a substantial burden of cardiovascular morbidity,” first author Kelly M. Kenzik, PhD, Institute for Cancer Outcomes and Survivorship, Division of Hematology and Oncology, University of Alabama at Birmingham, and colleagues wrote.

“Risk of morbidity increases with age and is influenced by exposure to FU and capecitabine and preexisting comorbidities. These findings provide evidence for close medical surveillance and the potential need for aggressive management of preexisting comorbidities of those with colorectal cancer who are at increased risk of cardiovascular morbidity,” added Kenzik, et al.

The research team analyzed data on Medicare-enrolled adults older than 65 years diagnosed with incident stage I to III colon or rectal cancer diagnosed from January 1, 2000, to December 31, 2011. Medicare claims were captured until death or December 31, 2013. Cumulative incidence functions, censoring for death, were used to assess the risk for new-onset CHF and CVD separately, as well as the risk for cardiovascular morbidity.

Women made up 55% of the study population, and 86% of the study population was white. Half of patients had been diagnosed with stage III colorectal cancer.

Investigators randomly selected a 5% noncancer sample of Medicare beneficiaries who resided in SEER catchment areas to serve as the control group.

Researchers discovered a significant interaction between hypertension and chemotherapy for CVD (P <.001) and between diabetes and chemotherapy for CHF (P <.001).

The use of capecitabine appeared to have a significant effect on cardiotoxicity risk. At less than 2 years since diagnosis, patients who received capecitabine alone were at a 3.65-fold increased risk for CHF (95% CI, 2.76-4.38) compared with those who received fluorouracil monotherapy. At 2 or more years since diagnosis, patients who received capecitabine alone were at a 1.57-fold increased risk for CHF compared with those who received fluorouracil alone.

However, patients who received capecitabine alone were at a lower risk for CVD compared with patients who received fluorouracil alone (HR, 0.63; 95% CI, 0.53-0.75) less than 2 years since diagnosis. Patients who received capecitabine alone were also at a lower risk 2 or more years since diagnosis (HR, 0.72; 95% CI, 0.62-0.84).

African-American race/ethnicity (HR, 1.22; 95% CI, 1.15-1.29; P <.001) and radiation therapy (HR, 1.30; 95% CI, 1.22-1.37; P <.001) were associated with significantly accelerated time to CHF. Preexisting comorbidities, except for hypertension, dyslipidemia, and liver disease, also independently accelerated the time to CHF.

Factors that significantly accelerated the time to CVD included African American race/ethnicity (HR, 1.17; 95% CI, 1.11-1.25; P <.001) and radiation therapy (HR, 1.18; 95% CI, 1.11-1.25; P <.001). All preexisting comorbidities, with the exception of liver disease, significantly accelerated time to CVD.

Kenzik KM, Balentine C, Richman J, et al. New-onset cardiovascular morbidity in older adults with stage I to III colorectal cancer [published online January 16, 2018]. J Clin Oncol doi: 1200/JCO.2017.74.97