Efficacy and safety of modified ECF regimen as first-line chemotherapy in metastatic gastric adenocarcinoma: A phase II study

Abstract

Background: ECF (Epirubicin, Cisplatin plus 5‐FU) is one of the most commonly used firstline chemotherapy regimens, in metastatic gastric cancer (MGC). But due to protracted infusion schedule of 5‐FU, need for special infusion pumps and catheter‐related complications; the practical utility and acceptability of standard ECF regimen is limited, particularly in resource‐constrained countries. Methods: In the present study, we have used a more convenient modification of the standard ECF protocol (by using 5 days IV infusion of 5‐FU at a dose of 750 mg/m /day, given over 6 hours through a peripheral venous line, every 3 weekly), in patients with MGC. The inclusion criteria were: age ≥18 years, pathologically proven MGC, ECOG PS ≤ 2; adequate organ functions and measurable disease according to RECIST 1.1. Major exclusion criteria were: previous chemotherapy for MGC, congestive cardiac failure and evidence of brain metastases. The primary endpoint was overall survival (OS). The secondary endpoints were overall response rate (ORR), progression‐free survival (PFS) and toxicity profile. The adverse events were classified based on the CTCAE v 4.0. Results: Between January 2014 and March 2018, 94 patients were treated with this modified ECF regimen. The median age was 52 years (range, 34‐62); 65% were males and 38.3% of the patients had ≥3 metastatic disease sites involvement at baseline. Dose reductions due to toxicity were required in 12.8% of the patients. The ORR was 34%; median PFS and OS were 5.7 months (95% CI: 4.4‐6.2) and 10.4 months (95% CI: 8.0‐11.7), respectively. Both the hematological and non‐hematological toxicities were manageable and there was no toxicityrelated death. The most common ≥grade 3 AEs were neutropenia (20%), febrile neutropenia (13%), mucositis (5%) and diarrhea (5%). Conclusions: In this phase II study, the modified ECF regimen demonstrated significant efficacy with manageable toxicity profile in Indian patients with MGC. The survival outcomes of this modified schedule were comparable with those of the standard ECF regimen, as reported earlier. Clearly, this modified and more convenient ECF protocol should be explored and validated through prospective randomized trials.