646P - First Stage Analysis of Irinotecan, Capecitabine (Xeloda®), and Oxaliplatin (Ixo) As First-Line Treatment of Her2- Metastatic Gastric or Gastroesophageal Junction (Gej) Adenocarcinoma

Abstract

ABSTRACT Aim: Gastric cancer is the second leading cause of cancer-related mortality worldwide. Treatment includes combination chemotherapy regimens with an average life expectancy of 7-10 months but optimal agents and schedule remains controversial. We hypothesize that the triplet combination IXO will have a superior response rate to current standard triplet treatment options with tolerable toxicity. Methods: The Bryant and Day two-stage design was used in this open-label, non-randomized, multicentre phase II study with the dual primary endpoints being response rate and toxicity. 25 patients were enrolled in the first stage. Each cycle was 21 days with IV infusion of oxaliplatin and irinotecan on day 1 and oral capecitabine BID on days 2-15. The initial starting doses were I-160mg/m2/ X-950mg/m2 BID/ O-100mg/m2. Results: Of the 25 patients enrolled, 24 were eligible for toxicity and 23 were evaluable for efficacy. At the original starting doses, 78% of patients experienced grade 3/4 toxicity (n = 7/9), resulting in a protocol amendment changing the starting doses to I-120 mg/m, X-712.5 mg/m2 BID, and O-100mg/m2 (n = 15). The median number of cycles started was 7 (range 1-20). The incidence of grade 3/4 toxicity at the reduced starting dose was 40%. The most frequent grade 1-4 adverse events in all 25 patients were diarrhea (70.8%), nausea, fatigue, and vomiting (each 58.3%). Of the 25 patients, 2 patients had dose limiting toxicity in the first two cycles while fifteen had dose reductions during the course of their treatment. The overall response rate was 69.6% and disease control rate was 95.7% (2 complete responses, 14 partial responses, 6 stable, and 1 progressive disease by RECIST criteria). Median time to progression was 8.3 months; median survival was 14 months. Conclusions: This interim analysis demonstrates a high overall response rate of 69.6% with IXO which is higher than previously reported triplet therapies. Efficacy was not affected after an adjustment in starting doses. Recruitment will resume for a total of 50 patients to confirm optimal doses and efficacy. Disclosure: All authors have declared no conflicts of interest.