Severe esophagitis directly induced by accumulation of crizotinib-residue at the esophageal mucosa proven with polarizing microscope examination

Crizotinib demonstrates dramatic effects for the patients with echinoderm microtubule-associated protein-like 4 (EML4)-anaplastic lymphoma kinase gene (ALK) fusion or c-ros oncogene 1 (ROS-1) fusion-positive lung cancer, with some characteristic toxicities. Although several studies reported that serious esophagitis was induced by crizotinib, the detailed mechanisms and ways to ameliorate the esophagitis have not been clarified. In this report, we report two cases with lung cancer who had been treated with crizotinib and developed severe esophagitis. Polarizing microscope examination clearly revealed that the accumulation of crizotinib-residue in the esophageal biopsy samples at the second anatomical narrowing of the esophagus in both cases. Since it seemed that the accumulation of crizotinib-residue in the esophageal mucosa directly caused the esophageal inflammation, we recommended taking crizotinib with a large amount of water (more than 200 ml) and to stay sitting upright for 30 minutes after intake. After that, the esophagitis gradually improved and the patients could continue taking crizotinib without dose reduction or withdrawal. Our experiences suggest that this crizotinib-induced esophagitis could be easily prevented by proper administration of crizotinib

Phase II study of IRInotecan treatment after COmbined chemo‐immunotherapy for extensive‐stage small cell lung cancer: Protocol of IRICO study

Abstract Introduction Combined treatment using anti‐programmed death‐ligand 1 antibody (anti‐PD‐L1) and platinum‐etoposide is the current standard first‐line treatment for patients with extensive‐stage (ES) small cell lung cancer (SCLC). However, the best treatment for relapsed ES‐SCLC after the first‐line treatment remains unclear. There are some approved chemotherapeutic agents that can be used against ES‐SCLC, and treatment with irinotecan is well established as both a monotherapy and a combined therapy, in combination with platinum. Therefore, we conduct a phase II study with irinotecan in the second‐ or later‐line setting for patients with ES‐SCLC who have been previously treated with combined treatment. Methods Our study will enroll total 30 patients who are diagnosed with ES‐SCLC and have experienced disease progression after the combined treatment. Patients will receive irinotecan on days 1, 8, and 15, which will be repeated every 4 weeks. Doses of irinotecan (100/80/60 mg/m2) will be determined according to the type of UGT1A1 gene polymorphism, and the treatment will be discontinued following disease progression, intolerance, withdrawal of patient consent, and based on the investigator's decision. The primary endpoint of the study is the response rate, and the secondary endpoints are overall survival, progression‐free survival, and safety. Discussion Since the present first‐line treatment has been changed to the combined treatment, the second‐ or later‐line treatment should be re‐evaluated for patients with relapsed SCLC. Irinotecan is a major chemotherapeutic agent used for SCLC. This study demonstrates and re‐evaluates the clinical benefits of irinotecan after combined treatment with anti‐PD‐L1 and platinum‐etoposide for patients with ES‐SCLC. Registration details This study was registered in the Japan Registry of Clinical Trials (no. jRCT s071210090) on November 4, 2021