Impact of age on toxicity and efficacy of 5-FU-based combination chemotherapy among patients with metastatic colorectal cancer; a pooled analysis of five randomized trials

Int J Colorectal Dis. 2019 Oct;34(10):1741-1747. doi: 10.1007/s00384-019-03389-w. Epub 2019 Sep 6.

Abstract

Objective: To assess the impact of age on toxicity and efficacy outcomes of metastatic colorectal cancer treated with 5FU-based combination chemotherapy.

Methods: Project Data Sphere (PDS) platform has been accessed and de-identified datasets of the following clinical trials were downloaded (NCT00272051; NCT00305188; NCT00115765; NCT00364013; and NCT00384176). Multivariable logistic regression analysis was used to assess the impact of age (< 70 years versus ≥ 70 years) on the probability of different toxicities. Multivariable Cox regression analysis was additionally used to evaluate the impact of age (< 70 years versus ≥ 70 years) on overall and progression-free survival.

Results: Among a total of 3223 patients included in the current analysis, 2488 patients were < 70 years; while 735 patients were ≥ 75 years at randomization. Older age was associated with a higher probability of serious adverse events (OR (odds ratio) 0.649; 95% CI 0.545-0.772; P < 0.001), fatal adverse events (OR 0.416; 95% CI 0.299-0.579; P < 0.001), all-grade diarrhea (OR 0.834; 95% CI 0.699-0.994, P = 0.043), high-grade diarrhea (OR 0.734; 95% CI 0.577-0.933, P = 0.012), high-grade stomatitis (OR 0.500, 95% CI 0.290-0.861, P = 0.012), high-grade thrombocytopenia (OR 0.578; 95% CI 0.359-0.930, P = 0.024), all-grade neutropenia (OR 0.690; 95% CI 0.578-0.824, P < 0.001), and high-grade neutropenia (OR 0.661; 95% CI 0.549-0.796, P < 0.001). In a multivariable Cox regression analysis for factors affecting overall survival, older age was associated with worse overall survival (hazard ratio for younger age versus older age 0.848; 95% CI 0.754-0.954, P = 0.006). On the hand, older age was not associated with worse progression-free survival (hazard ratio for younger age versus older age 0.933; 95% CI 0.843-1.032, P = 0.179).

Conclusion: Metastatic colorectal cancer patients ≥ 70 years of age who are treated with 5FU-based combination chemotherapy are more likely to have serious adverse events, fatal adverse events as well as worse overall survival compared to younger patients.

Keywords: Age; Colon cancer; Outcomes; Prognosis; Rectal cancer.

MeSH terms

  • Age Factors
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Colorectal Neoplasms / drug therapy*
  • Female
  • Fluorouracil / adverse effects*
  • Fluorouracil / therapeutic use*
  • Humans
  • Incidence
  • Male
  • Multivariate Analysis
  • Probability
  • Randomized Controlled Trials as Topic*
  • Regression Analysis
  • Survival Analysis
  • Treatment Outcome

Substances

  • Fluorouracil