Comparative effectiveness of adding metronidazole to chemoradiation in cervical cancer patients: a SEER-Medicare based study

Purpose: Metronidazole (MET) has been hypothesized to be a ‘radiosensitizer’, an agent that makes tumor cells more sensitive to radiation therapy (RT) thereby enhancing its efficacy. However there is currently no level I evidence from studies of large patient cohorts conducted within the last 10 years on cervical cancer patients with concurrent RT and MET use in the United States. We conducted a population-based retrospective comparative effectiveness analysis based on SEER-Medicare database to determine whether the addition of MET to concurrent radiation/chemoradiation improve survival in patients with cervical cancer.

Methodology: Women aged 18 and above with stage I-IV cervical uteri cancer diagnosed between 2009 and 2017 treated with radiation were identified in the SEER-Medicare database. Individuals receiving MET during their RT, for any duration, were considered to have been exposed to MET. Overall survival and cause-specific survival distributions were estimated using Kaplan-Meier methodology. Multivariable Cox regression analysis was used to adjust for potential confounders. A sensitivity analysis was performed after matching controls to MET-exposed individuals using an optimal matching procedure (Mamouris et al.). A two-tailed P value < 0.05 was considered statistically significant.

Results: The total cohort comprised of 1829 patients, of whom 75 received MET concurrent with RT. The overall survival (HR 1.22 (0.88, 1.68), p=0.13) and cause-specific survival (non-cancer HR 0.96 (0.46, 2.01), p=0.91; cancer HR 1.29 (0.89, 1.87), p=0.17) were not statistically different between MET exposure groups. 73 pairs were identified after matching which accounted for staging, chemotherapy status, age, race, poverty status and diagnosis year. Concurrent MET was still not associated with any overall survival (HR 1.19 (0.70, 2.00), p=0.52) or cause-specific survival (non-cancer HR 1.49 (0.48, 4.57), p=0.49; cancer HR 1.12 (0.63, 2.00), p=0.70) benefit.

Conclusions: In this comparative effective analysis of cervical cancer patients from SEER-Medicare database, the addition of metronidazole during radiation/chemoradiation treatment does not improve overall survival or cause-specific survival.

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