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Outcomes of metastatic colorectal cancer patients in relationship to prior and concurrent antibiotics use; individual patient data analysis of three clinical trials

Abstract

Background

Antibiotic use at the time of chemotherapy has been linked with inferior outcomes among a number of solid tumors. The current study aims at further assessing this observation among metastatic colorectal cancer patients treated with first-line systemic chemotherapy.

Methods

This is a pooled analysis of three clinical trial datasets (NCT00384176; NCT00272051; NCT00305188) that were accessed from the Project Data Sphere platform. Kaplan–Meier survival estimates were used to evaluate the impact of antibiotic use on overall and progression-free survival and multivariable Cox regression models were employed to further assess this impact.

Results

A total of 1446 patients were included in the current analysis. These include 108 patients who received antibiotics before the start of chemotherapy, 499 patients who received antibiotics after the start of chemotherapy, and 839 patients who did not receive antibiotics. Using Kaplan–Meier survival estimates, the use of antibiotics prior to the start of chemotherapy was associated with worse progression-free (P = 0.001) and overall survival (P < 0.001). Likewise, when multivariable Cox regression analyses were conducted, prior antibiotic use is associated with worse progression-free (HR for antibiotic use during chemotherapy versus antibiotic use prior to chemotherapy = 0.764; 95% CI 0.604–0.966; P = 0.024) and overall survival (HR for antibiotic use during chemotherapy versus antibiotic use prior to chemotherapy = 0.710; 95% CI 0.537–0.940; P = 0.017).

Conclusion

Antibiotic use before (but not following) the start of 5FU-based chemotherapy is associated with worse progression-free and overall survival among patients with metastatic colorectal cancer.

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Data availability

The data that support the findings of this study are openly available in https://www.projectdatasphere.org.

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Acknowledgements

This publication is based on research using information obtained from https://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 O. Abdel-Rahman.

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All authors declare that they have no competing interest.

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Ethical approval was obtained from all participating centers in the three clinical trials included in the current analysis.

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Informed consent was obtained from all participants in the three primary clinical trials.

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Abdel-Rahman, O., Ghosh, S. & Walker, J. Outcomes of metastatic colorectal cancer patients in relationship to prior and concurrent antibiotics use; individual patient data analysis of three clinical trials. Clin Transl Oncol 22, 1651–1656 (2020). https://doi.org/10.1007/s12094-020-02301-1

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  • DOI: https://doi.org/10.1007/s12094-020-02301-1

Keywords

  • Antibiotics
  • CRC
  • Chemotherapy
  • Prognosis
  • Outcomes