SIRT therapy with Yttrium-90 resin microspheres in patients with liver cirrhosis Child Pugh B7-9 and unresectable nonmetastatic hepatocellular cancer

Abstract

Introduction: Apatinib, a small molecule oral tyrosine kinase inhibitor (TKI) that mainly targets vascular endothelial growth factor receptor-2, has been approved in the treatment of advanced gastric cancer in China. Whereas, many patients treated with apatinib experienced toxicity necessitating dose reduction. Maintaining adequate dosing and drug levels are essential for optimizing clinical efficacy. Thus, it is urgently needed to explore optimal dosing strategy of apatinib treatment in advanced gastric cancer. Other small molecule TKIs such as sunitinib [J Clin Oncol, 27 (22): 3584-3590], sorafenib [Future Oncol, 13(8): 679-693] and anlotinib [J Hematol Oncol, 9(1): 105] have demonstrated efficacy and acceptable tolerability in advanced cancers via an intermittent dosing schedule. The current study was conducted to compare the efficacy and safety of intermittent (5days on/2 days off schedule) vs continuous apatinib therapy in combination with docetaxel as second-line treatment for advanced gastric cancer. Methods: This study is designed as an open-label, randomized clinical trial. To enroll, patients are required to have pathologically or histologically confirmed advanced gastric cancer and have experienced treatment failure with first-line chemotherapy. Other inclusion criteria include !18 years; Eastern Cooperative Oncology Group performance status of 0-2; life expectancy more than 3 months. Eligible patients are randomized to the treatment arms in a ratio of 1:1. In intermittent dose schedule, patients receive oral apatinib 500 mg/d for 5 days followed by 2 days off treatment. In continuous dose arm, patients received oral apatinib 500 mg/d as a continuous daily dosing. Docetaxel 60 mg/m2 is administered intravenously to patients on day 1 in a 21-day cycle in both groups. Treatment is continued until disease progression, intolerable toxicity or withdraw of consent. The primary outcome is progression free survival. The secondary outcomes include objective response rate, disease control rate, overall survival, quality of life and safety. Tumor response is assessed according to Response Evaluation Criteria in Solid Tumors guideline version 1.1. The incidence and severity of adverse events are defined by the Common Terminology Criteria for Adverse events version 4.0. Approximately 60 patients will be enrolled, with 30 subjects in each arm. Enrollment opened on September, 2017. As the cutoff date of February 27 2018, 19 patients were enrolled: 11 patients in the intermittent dose arm and 8 patients in the continuous dose arm. Clinical trial information: NCT03334591.