P-066S-1 in combination with epirubicin and oxaliplatin (EOS) in Caucasian patients (pts) with advanced or metastatic gastric cancer (AGC): Results of a phase I study

Introduction: S-1, an oral fluoropyrimidine registered in Europe, has demonstrated good efficacy and safety profile in the treatment (trt) of AGC in combination with cisplatin (FLAGS Study; J.A. Ajani. EJC2013). Triplets adding epirubicin to a fluoropyrimidine and platinum backbone (ECF, ECX, EOX or EOF) are also commonly used in AGC. We performed a phase I study evaluating S-1 with fixed doses of oxaliplatin (130 mg/m2 D1) and epirubicin (50 mg/m2 D1) q3w (EOS) in advanced or metastatic gastrointestinal cancer (AGIC) pts [cohorts 1 (C1) and 2 (C2)] and in chemo-naïve AGC pts [cohort 3 (C3)]. After complete results were presented for C1 and C2 at ASCO-GI 2015 (abstract 140), we now report the results of cohort C3 in AGC only. Methods: Pts >18 years, ECOG/PS 0/1 were enrolled. Standard dose- limiting toxicity (DLT) evaluation was used. The maximum tolerated dose (MTD) was defined as the highest dose level at which less than <2/6 pts experienced a DLT during Cycle 1. In C1 and C2, which enrolled heavily pretreated AGIC, the recommended dose of S-1 was 20 mg/m2/BID. In C3, pts received 25 mg/m2/BID and results are reported here. Results: During cycle 1, no DLT occurred among the first 6 patients enrolled in C3 and the cohort was then expanded up to 12 pts. Regarding related toxicities, 1 pt experienced grade 3 neutropenia, 2 pts had a grade 2 neutropenia, and 1 had grade 2 nausea. Other related toxicities were only grade 1: nausea and/or vomiting (3pts), alopecia (2 pts), diarrhea, anorexia and fatigue (1 pt each). No hand foot syndrome or cardiovascular toxicities were reported. All pts, except one, received 3 cycles or more and 5, 12 cycles or more. After 8 EOS cycles, 6 patients were still on treatment with S-1 monotherapy as maintenance: 9 cycles (1), 12 cycles (3), 13 cycles (1) and 15 cycles (1) and all has stable disease. At the time of the presentation, more data on safety, efficacy, response, PFS and OS will be available. Conclusion: Based on these promising results, the recommended dose of S-1 with fixed doses of oxaliplatin (130 mg/m2 D1) and epirubicin (50 mg/m2 D1) q3w in chemo-naïve AGC pts is 25 mg/m2/BID during 14 days every 3 weeks. Thus, this EOS regimen represents a safe and efficient alternative first line treatment in advanced or metastatic AGC.