Combined Metronomic Chemo-Immunotherapy in Metastatic Carcinoma of Esophagus in Second Line and Beyond

Abstract

Background and Aims: Approximately 570,000 new cases are diagnosed with esophageal cancer worldwide annually and approximately 510,000 deaths from this disease per year. There are currently no effective second-line treatments for patients who progress on cisplatin and 5-fluorouracil. Esophageal squamous cell carcinomas and adenocarcinomas have proven to be inherently resistant to systemic treatments as a result of histological, molecular and etiological heterogeneity, with limited responses seen after first line therapy. Methods: We are presenting 3 case reports of 57 year old man, 53 year old man & 47 year old woman who, presented with dysphasia for solid foods, weight loss and dyspepsia since 1 month, 3 months & 1.5 months respectively. Upper gastro oesophageal endoscopy shows ulcerated friable lesion with minimal luminal compromise with biopsy showing poorly differentiated adenocarcinoma (PDAC) and PECT-CT showed FDG avid lesions in gastroesophageal junction, gastric cardia, multiple retroperitoneal lymph nodes and bilateral liver lesions. All 3 were having stage IV disease, with PDAC, squamous cell carcinoma & PDAC respectively. We have started 1st patient on DOX regimen containing Docetaxel, Oxaliplatin and Capecitabine at an interval of 2 weeks and after 4 cycles he was having stable disease in GE junction, liver and slightly increased size of retroperitoneal lymph nodes. Second & 3rd patient was put on Pclitaxel-carboplatil protocol, after 6 cycles both were having partial response & was managed with 6 cycles CAPOX as second line che otherapy. After 5th & 6th months of second line chemotherapy both patients were having progressive disease. Results: In view of radiological progression we started him on Injection, Nivolumab 240mg intravenously every 2 weekly along with low dose capecitabine 500mg twice a day. After 4 cycles of treatment his PET-CT showing complete metabolic response in GE junction, liver and retroperitoneal lesions. Now we are continuing Nivolumab and low dose capecitabine planned to complete for 2 years. Conclusion: So to conclude nivolumab along with metronomic chemotherapy with low dose capecitabine was very well tolerated and exhibited antitumor activity in extensively pretreated patient with metastatic esophageal poorly differentiated adenocarcinoma. Additional studies of Nivolumab and metronomic chemotherapy and immuno-immuno combination therapy in these diseases are ongoin.