A Phase I Dose Escalation Study of Apatinib Combinated with Docetaxel as Second-line Therapy for Advanced Gastric Carcinoma

Abstract

This study is a phase I clinical trial of 3+3 dose escalation. Three dose escalations of apatinib were employed in this study: 425 mg, 500 mg and 675 mg. Apatinib combined with fixed dose of docetaxel (60 mg/m2, d1, thrice inw). 21 d as one treatment cycle was repeated. Maximum tolerated dose, safety and efficacy were analyzed. From October 2015 to June 2017, a total of eight patients with advanced gastric or gastro-oesophageal junction adenocarcinoma who had failed in the previous first-line treatment were enrolled. One dose-limiting toxicity was observed in patients who received apatinib with the dose of 425 mg combined with docetaxel, but no dose-limiting toxicity was found in additional three patients. Two patients treated with apatinib at the dose of 500 mg combined with docetaxel experienced dose-limiting toxicity, including grade 3 oral mucositis and grade 4 neutropenia respectively. Therefore, Maximum tolerated dose of apatinib was 425 mg. No complete response and partial response were observed; five patients showed stable disease and two had progressive disease. The disease control rate was 71.43 %. The median progression free survival was 4.4 mo (95 % confidence interval, 1.48-7.03) and the median overall survival was 11.5 mo (95 % confidence interval, 3.06-16.56). All patients developed adverse events and treatment-related adverse events. Seven patients (77.78 %) showed treatment-related adverse events greater than or equal to grade 3, mostly including neutropenia and hand-foot syndrome. The combination of apatinib with the dose of 425 mg and docetaxel was well tolerated and support further evaluation for the second-line treatment of advanced gastric cancer.