PURPOSE Gemcitabine-based chemotherapy is standard for metastatic pancreatic ductal adenocarcinoma (PDAC), but resistance limits its efficacy. Bacteria in the PDAC tumor microenvironment may contribute to resistance. Hence, the coadministration of an antibiotic to chemotherapy may potentiate antitumor drug responses. This study evaluates the safety and efficacy of adding ciprofloxacin to gemcitabine-based chemotherapy. Secondary aims included stool microbiome and exhaled breath volatile analysis. MATERIALS AND METHODS This single-arm study at the National University Cancer Institute, Singapore, enrolled patients with treatment-naïve advanced PDAC. Patients received nab-paclitaxel (125 mg/m 2 ) and gemcitabine (1,000 mg/m 2 ) administered weekly on days 1, 8, and 15 of each 4-week cycle, together with oral ciprofloxacin (500 mg twice daily) until disease progression or intolerable toxicity. Stool and tumor samples were subjected to 16S rRNA sequencing. Primary end points were response rate and safety. Secondary end points included progression-free survival (PFS), overall survival (OS), and microbiome changes. RESULTS From March 2019 to February 2021, 8 patients were recruited. Best response was stable disease in 5 (62.5%) patients, and 3 patients had progressive disease (PD). The median PFS and OS were 4.3 and 15.4 months, respectively. Two patients developed grade 4 neutropenia and one had grade 3 febrile neutropenia. A total of 50% of patients developed grade 1/2 rash. No additional toxicities from ciprofloxacin were observed. PD correlated with increased Gammaproteobacteria and decreased cytidine deaminase functional potential. Response to therapy was associated with baseline increased abundances of Firmicutes species. CONCLUSION Gemcitabine-based chemotherapy plus ciprofloxacin demonstrated clinical activity and an acceptable safety profile in PDAC. Lack of response to treatment was associated with increased abundances of Gammaproteobacteria .
Cheo et al. (Wed,) studied this question.