Efficacy and Safety of FOLFOX as a Second-Line Chemotherapy for Patients with Locally Advanced and/or Metastatic Carcinoma Gall Bladder – Experience from a Tertiary Care Center in India

Abstract

Abstract Background: Carcinoma gallbladder is mostly diagnosed in locally advanced, inoperable, or metastatic stage. Best supportive care with or without palliative chemotherapy is the only feasible treatment option. Gemcitabine and platinum agents' combination is the most effective first option with no well-established second-line regimen. Objectives: We planned to study the response rate, safety, the progression-free survival (PFS), and overall survival (OS) on the second-line FOLFOX-4 chemotherapy. Methods: This is a prospective single-arm observational study of 29 eligible patients. Patients were studies for response to the second-line FOLFOX-4 chemotherapy. Positron emission tomography/computed tomography scans were done for response assessment; chemotherapy toxicity was graded using National Cancer Institute clinical toxicity criteria; and survival rates (PFS and OS) were studied. Results: Among the 39 patients with gemcitabine-based chemotherapy (CT-1), the median PFS-1 was 6.5 months. Twenty-nine patients received second-line chemotherapy (CT-2). Responses observed complete response in 2/29, partial response in 7/29, stable disease in 1/29 patients, and progressive disease in 19/29. The overall response rate was 9/29 (31.0%). Grades 2–4 toxicities were anemia (17.95%), thrombocytopenia (12.82%), neutropenia (12.82%), and peripheral neuropathy (7.69%). The median OS was 9.13 months. Late PFS-1 (>median PFS-1) patients had significantly lower mortality as compared to early PFS-1, odds ratio of 0.251 (P = 0.002), and median PFS-2 was 2.53 months. Conclusion: After the failure of gemcitabine and platinum-based chemotherapy, FOLFOX-4 is modestly effective, fairly well tolerated and this needs to be proven in a larger randomized phase 3 study. Further research into the pathogenesis of biliary tract cancer with the aim to identify new targets for treatments is required.