Oxaliplatin, irinotecan, bevacizumab followed by docetaxel, bevacizumab in inoperable gastric cancer: First efficacy results of a multicenter phase II trial (AGMT Gastric-3) of the Arbeitsgemeinschaft Medikamentöse Tumortherapie.

Abstract

4074 Background: In our previous phase II trials (AGMT-Gastric-1 and AGMT Gastric-2) efficacy of oxaliplatin and irinotecan as well as oxaliplatin, irinotecan and cetuximab was shown. Time to progression however was short suggesting acquired chemotherapy resistance. Therefore sequential chemotherapy combined with bevacizumab is investigated in the presented trial. Methods: Oxaliplatin 85 mg/m2 biweekly (q2w) and irinotecan 125 mg/m2 q2w are administered for the first three months followed by docetaxel 50mg/m2 q2w for three months. Chemotherapy for 6 months is combined with bevacizumab 5 mg/kg q2w which is administered until progression. For this abstract 36 patients (pt.) with histologically proven unresectable and/or metastatic gastric adenocarcinoma have been evaluated in a first line setting. Median age: 62.5 years (range 26-80 years), PS 0: 25 patients, PS 1: 10 patients, missing: 1 patient, single metastatic site: 24 patients, multiple metastases: 10 patients, missing: 2. Results: Frequently reported adverse events (more than 20% of pt.) were predominantly grade 1 or 2 and included diarrhea (25/36, 69%), polyneuropathy (17/36, 47%), nausea (17/36, 47%), fatigue (15/36, 42%), neutropenia (13/36, 36%), abdominal pain (11/36, 31%), hypokalemia (9/36, 25%). Grade 3 and 4 toxicities included neutropenia (6/36, 17%), diarrhea (3/36, 8%), hypokalemia (3/36, 8%), anemia in (2/36, 6%), leucopenia (2/36, 6%), thrombocytopenia (1/36, 3%), nausea in (1/36, 3%). Objective response rate after 3 cycles was available in 25 patients: CR 1/25 (4%), PR 14/25 (56%), SD 8/25 (32%), PD 2/25 (8%). After 6 cycles there were 12 evaluable patients with CR 2/12 (16.7%), PR 5/12 (41.7%), SD 4/12 (33.3%) and PD 1/12 (8.3%). Conclusions: The combination of oxaliplatin and irinotecan with bevacizumab followed by docetaxel with bevacizumab is feasible and very active in advanced gastric cancer.