A multicenter phase II study of TAS-114 in combination with S-1 in patients with pretreated advanced gastric cancer (EPOC1604).

BACKGROUND: This is a phase 2 study aimed at evaluating the efficacy and safety of TAS-114, a novel deoxyuridine triphosphatase inhibitor, combined with S-1 in patients with advanced gastric cancer (AGC). METHODS: Eligible patients had AGC with measurable lesions, according to the Response Evaluation Criteria in Solid Tumors (RECIST, v1.1), with two or more previous chemotherapy regimens including fluoropyrimidines, platinum agents, and taxanes or irinotecan. The primary endpoint was objective response rate (ORR) according to the RECIST, v1.1. Twenty-nine patients were required according to Simon's optimal two-stage design, with one-sided a = 5% and power = 80%. Threshold and expected ORRs were 5% and 25%. Patients received TAS-114 (400 mg/body, twice a day) and S-1 (30 mg/m2, twice a day) for 14 days, followed by 7 days of rest in one 3-week cycle. Protein expression levels of dUTPase and BRCA1 in tumor samples were determined by immunohistochemistry. RESULTS: Accrual was terminated in June 2018 because meeting the predefined efficacy criteria was considered difficult. ORR and disease control rate were 5.0% [95% confidence interval (CI), 0.1-24.9%] and 70.0% (95% CI, 45.7-88.1%), respectively, for all 20 patients enrolled. Median progression-free survival (PFS) and overall survival were 2.4 months (95% CI, 1.2-3.3 months) and 7.1 months (95% CI, 5.2-9.4 months), respectively. Median PFS in the groups with high and low dUTPase protein expression in the cytoplasm was 2.8 months (95% CI, 1.4-3.9) and 1.6 months (95% CI, 0.6-2.4), respectively [hazard ratio, 0.40 (95% CI, 0.16-1.04), log-rank test two-sided p = 0.047]. Grade 3 or higher treatment-related adverse events included anemia (20%), leucopenia (15%), neutropenia (10%), rash (10%), thrombocytopenia (5%), and lymphopenia (5%) CONCLUSIONS: TAS-114 with S-1 showed only modest antitumor activity with acceptable safety profiles for patients heavily pretreated with AGC.

[Relative dose intensity of FOLFOX4 regimen].

PURPOSE: Oxaliplatin (L-OHP) is one of the key drugs against advanced, recurrent colorectal cancer, and FOLFOX4 regimen combination of l-leucovorin (l-LV)and 5-fluorouracil (5-FU)with oxaliplatin is a standard therapy in colorectal cancer. We performed a retrospective study that researched adverse events and relative dose intensity(RDI)to evaluate safety and feasibility of FOLFOX4 regimen. PATIENTS AND METHODS: We administered 188 patients a FOLFOX4 regimen. To evaluate RDI, this study research dose modification and delay treatment procedure was done for 1 to 13 cycles. RESULTS: RDI of oxaliplatin is 89.1% (1-4 cycles), 81.4% (4-7 cycles), 78.2% (7-10 cycles), 69.0% (10-13 cycles). The factors of RDI decrease were hematologic toxicity(leucopenia, neutropenia, thrombocytopenia), peripheral neuropathy and allergic reaction. Moreover, peripheral neuropathy and allergic reaction often require therapy to be discontinued (peripheral neuropathy: 15.2%, allergic reaction: 20.3%). CONCLUSION: Feasibility of FOLFOX4 regimen is related to incidents of hematologic toxicity, peripheral neuropathy and allergic reaction. We should pay sufficient attention to these adverse events of FOLFOX4.