Do systemic antibiotics affect the effectiveness of chemotherapy for malignant cancers? - A cohort study based on CPRD and Cancer Registry data

Date of ISAC Approval: 
Lay Summary: 
Gut microbiota consists of more than 1,000 different bacterial species. These bacteria are important for digestion and overall health. Antibiotic treatment can disturb the gut microbiota and kill many of the bacteria in the gut. There is scientific evidence that suggests that disturbance of the gut microbiota could reduce the effectiveness of chemotherapy and immunotherapy for cancers (i.e., medicines that kill dividing cells such as cancer cells in the body). This evidence examined the effects of antibiotics on microbiota in either mice or tissues. There is limited evidence in humans about whether antibiotics affect the effectiveness of cancer chemotherapy. This study aims to use UK-based Clinical Practice Research Datalink (CPRD) to evaluate the association between recent use of antibiotics and their impact on overall mortality of recently diagnosed cancer patients. Patients who had been previously exposed to oral and/or intravenous antibiotics with no cancer history from 2000, with at least 3 years of follow-up after the data collection, and who developed incident cancer, will be our cases. We will evaluate the proportion of cases who die after the diagnosis of cancer. We will compare cases with recent antibiotics use with cancer patients that used antibiotics in the distant past.
Technical Summary: 
We propose to conduct a cohort study. The cohort will consist of patients with an incident diagnosis of different types of cancer who have been exposed to oral and/or intravenous antibiotics prior to the index date of the cancer diagnosis. The rate of mortality after the cancer diagnosis will be compared between recent and past antibiotic users. Cancer patients with specific comorbidities for which there is evidence that they can act as potential confounders will be excluded based on READ codes. Data linkages between CPRD, Office of National Statistics (ONS) Mortality data and Cancer Registry data will be used. The analysis will be based on Kaplan-Meier plots and Cox regression modelling, estimating how survival is affected by past antibiotics exposure (and indirectly microbiota) before cancer onset.
Health Outcomes to be Measured: 
- How does recent antibiotic exposure impact chemotherapy Treatment and associated Mortality of patients with A new diagnosis of cancer - Drug effectiveness - cancer Incidence

Professor Tjeerd van Staa - Chief Investigator - University of Manchester
Professor Andrew G Renehan - Collaborator - The Christie NHS Foundation Trust
Professor Darren Ashcroft - Collaborator - University of Manchester
Ms Eleni Domzaridou - Collaborator - University of Manchester
Taher Hamid - Collaborator - University of Manchester
Victoria Palin - Corresponding Applicant - University of Manchester

Cancer Registration Data;ONS