A Phase I Dose Escalation Study of Apatinib Combinated with Docetaxel as Second-line Therapy for Advanced Gastric Carcinoma
Department of Oncology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou 310016, China
H. Pan, Department of Oncology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou 310016, China, E-mail: email@example.com
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.