The test is a procedure that measures the proliferation of drug-specific T cells em in vitro /em . carcinoma (HCC) patients who show progression under sorafenib treatment (1). However, the use of regorafenib is only recommended for patients who have tolerated sorafenib. We herein present the case of a patient in whom regorafenib could be continued for 10 months without severe adverse events after the discontinuation of sorafenib due to hypersensitivity. Case Report The patient was a 58-year-old man who was taken to a local hospital with acute abdominal pain in July 2011. Contrast-enhanced computed tomography (CT) revealed a ruptured tumor of 33 mm in diameter in hepatic segment 2. Hepatectomy was performed and a pathological examination of the resected specimen revealed moderately differentiated HCC without vascular invasion. The surrounding tissue was cirrhotic, which was considered to be the result of chronic alcohol abuse. Assessments for hepatitis B surface antigens, hepatitis C antibodies and anti-nuclear antibodies were negative. He had no comorbidities and was not receiving medication for any conditions other than liver disease. In 2015, radiofrequency ablation and BIO-5192 transarterial chemoembolization (TACE) were BIO-5192 performed to treat regional recurrence. He was referred to our hospital for further management in January 2016. On presentation to our hospital, his Eastern Cooperative Oncology Group performance status (ECOG-PS) score of 0 and his Barcelona Clinic Liver Malignancy classification (BCLC) BIO-5192 stage was C with multiple intrahepatic recurrences and peritoneal dissemination. Liver function tests revealed a Child-Pugh score of 5 (Table 1). Sorafenib was started at a dose of 800 mg/day and was continued without symptoms. After 32 days, liver injury designed and sorafenib was discontinued. However, nausea and loss of appetite appeared, and the patient’s liver injury showed progression. Intravenous methylprednisolone (1,000 mg) was administered for 3 days, followed by oral prednisolone until the patient made a full recovery from the liver injury. Prednisolone was slowly tapered over one month and was discontinued (Fig. 1). At one month after the discontinuation of prednisolone, a drug-induced lymphocyte stimulation test (DLST) for sorafenib was unfavorable. The stimulation index (SI) was 107%. The actual values of the test wells and control wells were 273 counts per minute (cpm) and 253 cpm, respectively. Table 1. Laboratory Data at the Start of Sorafenib Treatment. White blood cell7,200/LALP216U/LRed blood cell4.38106/L-GTP52U/LHemoglobin13.7g/dLCholinesterase275U/LPlatelet144103/LTotal bilirubin1.0mg/dLTotal protein7.1g/dLPT-INR1.00Albumin3.8g/dLBUN11.1mg/dLAST21U/LCreatinine0.77mg/dLALT17U/LAFP7ng/mLLDH160U/LDCP136mAU/mL Open in a separate windows -GTP: -glutamyl transferase, AFP: -fetoprotein, ALP: alkaline phosphatase, ALT: alanine aminotransferase, AST: aspartate aminotransferase, BUN: blood urea nitrogen, DCP: des–carboxy protein, PT-INR: prothrombin time-international normalized ratio, LDH: lactate dehydrogenase Open in a separate window Physique 1. The clinical course of the patients alanine aminotransferase (ALT) and total bilirubin levels after sorafenib was initiated at a dose of 800 mg/day. After 32 days, liver injury develops. The ALT and total bilirubin levels were 874 U/L and 1.7 mg/dL, respectively. At two weeks after stopping sorafenib treatment the liver injury had worsened; the patients ALT and total bilirubin levels were 1,665 U/L and 10.1 mg/dL, respectively. The patient was then given intravenous methylprednisolone (1,000 mg) for 3 days, followed by oral prednisolone until the patient made a full recovery from liver injury. Prednisolone was then slowly tapered over one month and discontinued. Contrast-enhanced CT during sorafenib treatment showed that most of the tumors changed from high-density to iso-density in the early arterial phase, and it was predicted that sorafenib would have an effect. In August 2016, sorafenib was restarted at a low dose of 200 mg/day with safety in mind. Around the 5th day after restarting sorafenib, the patient developed a fever of 40. The fever resolved quickly after the discontinuation of sorafenib. There was no skin disorder, eosinophilia, or liver injury. The DLST for sorafenib was repeated, and the result was positive (SI: 380%; actual values: 650 cpm/171 cpm). Treatment with uracil-tegafur, TACE for intrahepatic recurrence, and transcatheter arterial infusion for peritoneal metastasis were carried out. However, the response, according to the Response Evaluation Criteria in Solid Tumors, was progressive disease. Mouse monoclonal to CER1 In June 2017, regorafenib was approved for the treatment of HCC in Japan. The approval was based on the results of the RESORCE trial, which used distinct criteria to include patients who tolerated sorafenib. Although the patient did not fulfill the criteria, he requested regorafenib treatment since no other systemic therapies were available. A multidisciplinary team was consulted, and it was thought that the absence of hypersensitivity to regorafenib should be confirmed before its.