Comparison of efficacy and safety of second-line palliative chemotherapy with paclitaxel plus raltitrexed and paclitaxel alone in patients with metastatic gastric adenocarcinoma: a randomized phase 2 clinical trial

Abstract

BackgroundPaclitaxel is a microtubule stabilizing agent, used as standard second line chemotherapy in the treatment of advanced gastric cancer. This study was designed to compare the clinical outcome of paclitaxel plus raltitrexed regimen as second line treatment in MGC patients.MethodsAn open, randomized, multi centers phase II clinical trial. 148 patients were randomly assigned and treated with either RP (raltitrexed 3 mg/m2 day1 and paclitaxel 135 mg/m2 day1, 3week) or P (paclitaxel 135 mg/m2 day1, 3week) as second-line palliative chemotherapy. The primary endpoint is PFS; secondary endpoint is ORR, OS and safety.ResultsProgression free survival has a tendency to be prolonged with RP versus P (2.7month vs. 1.7month, p = 0.148). Overall survival has also a tendency to be prolonged with RP versus P (10.2month vs. 6.1month, p = 0.140). Overall response rate was equal with RP versus P (6.8% vs.4.0%, p = 0.72). DCR in the RP and P group was 56.2% and 36.0% respectively. Grade 3 to 4 treatment-related adverse events occurred in 36.2% (RP) vs. 28.2% (P) of patients. Frequent grade 3 to 4 toxicities for RP vs. P were: neutropenia (11.0% vs. 4.0%), anemia (1.4% vs. 4.0%), thrombocytopenia (1.4% vs. 5.3%), and all grade peripheral neurotoxicity (12.3% vs. 17.3%). All grades found with elevated aminotransferase (27.4% vs. 14.1%). Subgroup analysis shows if the disease combined with ascites or peritoneal involved OS of RP regimen is longer (p = 0.05).ConclusionsSecond-line palliative chemotherapy with paclitaxel plus raltitrexed have tendency to prolong PFS and OS, especially some patients with ascites or peritoneal involved, which needs to be confirmed by larger sample studies.Trial registrationNCT02072317. Registered 26 February 2014