Phase II trial of capecitabine and everolimus (RAD001) combination in refractory gastric cancer patients

Background The aim of this study was to assess the efficacy and safety of combination regimen of capecitabine plus everolimus in patients with refractory gastric cancer who have failed to at least two cytotoxic regimens. Methods Patients received capecitabine 650 mg/m(2) twice daily (D1-14) and everolimus 5 mg twice daily (D1-21) every 3 weeks until disease progression or unacceptable toxicity. The primary endpoint of the study was overall response (partial or complete response) and the secondary endpoints were progression-free survival (time between registration and disease progression or death) and overall survival. Pharmacokinetic analysis was also performed. Patients who have failed to at least two cytotoxic regimens were enrolled. Results Between March 2010 and June 2012, 47 patients were enrolled. 33 patients (70.2 %) had received more than three previous regimens prior to enrolment. Among 43 evaluable patients for treatment response, 5 patients achieved confirmed partial response and 18 patients showed stable disease, resulting in an overall response rate (ORR) of 10.6 % (95 % C.I.: 1.8-19.4 %) and disease control rate of 48.9 % (95 % C.I.:34.6-63.2 %). At a median follow-up of 106 weeks (range, 21-141 weeks), the median progression-free survival and overall survival were 11.0 weeks (95 % C.I.: 5.7-16.3 weeks) and 21.0 weeks (95 % C.I.: 14.3-27.7 weeks), respectively. Grade 3 nausea, diarrhea and stomatitis occurred in two, three and three patients, respectively. Elevated liver enzyme was observed in 21 patients and no patient had pulmonary fibrosis. Conclusions The combination of capecitabine 650 mg/m(2) twice daily and everolimus 5 mg twice daily was found to be effective in a small subset of GC patients who were heavily pre-treated.