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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

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.

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Acknowledgments

This publication is based on research using information obtained from www.projectdatasphere.org, which is maintained by the Project Data Sphere, LLC. Neither Project Data Sphere, LLC nor the owner(s) of any information from the website have contributed to, approved, or are in any way responsible for the contents of this publication.

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Correspondence to Omar Abdel-Rahman.

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All procedures performed were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Informed consent was obtained from all participants included in the study.

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Abdel-Rahman, O., Karachiwala, H. 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 34, 1741–1747 (2019). https://doi.org/10.1007/s00384-019-03389-w

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  • DOI: https://doi.org/10.1007/s00384-019-03389-w

Keywords

  • Age
  • Prognosis
  • Colon cancer
  • Rectal cancer
  • Outcomes