Objectives We wished to assess if low-dose daily oral metronidazole reduced the risk of malignant vesico-vaginal (VVF) and recto-vaginal fistulae (RVF) in recurrent cervical cancer.
Methods From a ten-year historic cohort in our teaching hospital, we identified 208 patients with pelvic recurrence of cervical cancer. Seventy six patients had been prescribed oral metronidazole 200 mg once daily for malodor control. We compared fistula-free survival and post-recurrence survival in patients who had received, or not received, low dose (metronomic) metronidazole.
Results Seventy two patients developed malignant fistulae (49 VVFs; 10 RVFs and 13 with both VVF and RVF). Metronomic metronidazole was associated with fewer fistulae (22.4% versus 41.7%); a longer fistula-free survival [42.9 months (95% CI, 10.2 m to 75.6 m); versus 14.1 months (95% CI, 7.7 m to 20.4 m); P<0.001]; and a trend to improved post-recurrence survival.
In the subset (n=146) followed until death, on multivariate analysis, metronomic metronidazole remained significantly associated with a longer post-recurrence survival [hazard ratio 0.56; 95%CI, 0.39–0.81; P=0.002] and a longer fistula-free survival [hazard ratio 0.34; 95%CI, 0.17–0.69; P=0.003].
Conclusions Daily low-dose oral (metronomic) metronidazole is a simple and inexpensive intervention. Reduction in inflammation, malodor and necrotic discharge, and decreased liquefactive destruction of visceral tissue planes probably led to better fistula and survival outcomes in this retrospective study.
Our findings suggest that it would be worthwhile to conduct a randomized trial comparing fistula, malodor, radiotherapy completion, local control and survival outcomes in recurrent or locally advanced cervical cancer with or without metronomic metronidazole.
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