Esophageal cancer is one of the common malignant tumors. Different from that in western countries, esophageal squamous cell carcinoma (ESCC) is still the dominant pathological type in China and account for more than 95% of cases in clinic. The annual incidence of esophageal squamous cell carcinoma is 260,000 with the mortality of 210,000 in China. For patients with recurrent or metastatic disease, chemotherapy is one of important treatment alone or with radiotherapy. Taxane, platinum, and fluoropyimidine have been reported effective in ESCC and are popularly used in first-line treatment of ESCC. However, there is still no standard 2nd-line treatment for ESCC patients. Apatinib, also known as YN968D1, is an oral tyrosine kinase inhibitor to vascular endothelial growth factor (VEGFR) receptor, by which blocks the VEGF signaling pathway and results in anti-angiogenesis of tumors. Preclinical data has shown that it is effective in the treatment of a variety of solid tumors including esophageal cancer. And it was approved and launched in China in 2015 as a 3rd-line treatment for patients with advanced gastric cancer. However, the role of anti-angiogenses targeting treatment including apatinib is unknown. Here, we initialize a dose escalation phase I study to identify the dosage of apatinib when combined with irinotecan to treat ESCC patients who were with recurrent disease after esophagectomy and refractory to 1st-line chemotherapy.
Patients, age 18-70, with measurable tumor lesion, failed in or progression after 1st line chemotherapy, were enrolled in this 3 + 3 design study. Apatinib dosage escalated from 250 mg, 500mg, to 750mg daily in 3 different cohorts while the dosage of irinotecan was maintained 150mg/m2 very 2 weeks for 3 cycles (6 weeks). The dose-limiting toxicity (DLT) was identified as grade 4 hematologic toxicity and grade 3 to 4 non-hematologic toxicity according to NCI CTC AE 4.0 criteria. The primary endpoint is the maximum toxic dosage (MTD) and the secondary end points include the objective response rate (ORR), progression-free survival (PFS) and overall survival (OS).
Clinical trial identification
Legal entity responsible for the study
Dr. Xiaodong Zhang
HengRui Cancer Research Foundation of CSCO (Y-HR2015-030)
All authors have declared no conflicts of interest.