The comparison of mFOLFOX-6, mDCF, mFOLFIRINOX in the first-line treatment of advanced gastric cancer

The prognosis of patients (pts) with advanced gastric cancer is poor. There is no single, global standard regimen for the first-line treatment of metastatic disease. We performed a randomized trial to evaluate the safety and efficacy of first-line mFOLFOX-6, mDCF, mFOLFIRINOX in metastatic gastric cancer pts. Pts were randomly assigned to mFOLFOX-6 (оxaliplatin 85 mg/m2 IV on day 1, folinic acid 400 mg/m2 IV on day 1, fluorouracil (5-FU) 400 mg/m2 IV bolus, 5-FU 2400 mg/m2 IV continuous infusion over 46 hours), mDCF (docetaxel 40 mg/m2 IV on day 1, cisplatin 40 mg/m2 IV on day 1, 5-FU 2000 mg/m2 IV continuous infusion over 48 hours) and mFOLFIRINOX (Irinotecan 180 mg/m2 IV on day 1, оxaliplatin 85 mg/m2 IV on day 1, Folinic acid 200 mg/m2 IV on day 1, 5-FU 250 mg/m2 IV bolus, 5-FU 2200 mg/m2 IV continuous infusion over 46 hours). The primary endpoint was overall survival. Sample size: 178 pts in each arm to decrease rate of progression in mFOLFOXIRI/mDCF arms comparative to mFOLFOX-6 arm (HR 0.75, α = 0.05; β = 0.80; 10% of estimated data loss). We included 50 pts in the preliminary analysis: 20 pts in mFOLFOX-6 arm, 17 pts in mDCF arm, 13 pts in mFOLFIRINOX arm. Median age was 61 years (27-74). No complete responses were achieved. Disease control rate was 85% (17/20) in mFOLFOX-6 arm, 58,8% (10/17) in mDCF arm, 84% (11/13) in mFOLFIRINOX. Partial response rate was 30% (6/20) in mFOLFOX-6 arm, 17.6% (3/17) in mDCF arm, 23% (3/13) in mFOLFIRINOX arm. Pts in the mFOLFIRINOX arm had more frequent reduction in chemotherapy doses 61,5% (8/13) vs 15% (3/20) in mFOLFOX-6 arm and 17,7% (3/17) in mDCF arm. Grade 3–4 neutropenia was observed in 30% (6/20) of cases in mFOLFOX-6 arm, 23,5% (4/17) - in mDCF arm, 38,5% (5/13) - in mDCF arm. Pts in mFOLFIRINOX arm and mDCF arm received G-CSF. Rates of grade 3/4 non-hematologic adverse events (asthenia, cardiotoxicity, hepatotoxicity) were 46,2% (6/13) in mFOLFIRINOX arm, 5% (1/20) in mFOLFOX-6 arm. mFOLFOX was comparable in efficacy to three-drug chemotherapy regimens (mFOLFOXIRI/mDCF) in the first-line setting of advanced gastric cancer. mDCF arm was closed and changed to FLOT arm.