Oral S-1 with 24-h Infusion of Irinotecan plus Bevacizumab versus FOLFIRI plus Bevacizumab as First-Line Chemotherapy for Metastatic Colorectal Cancer: An Open-Label Randomized Phase II Trial

Abstract

Background: FOLFIRI plus bevacizumab have been widely used as first-line treatment for metastatic colorectal cancer (mCRC). Pharmacokinetics and pharmacodynamics suggested a low dose of irinotecan given as a long-term infusion is expected to enhance antitumor activity. We conducted a randomized phase II study to compare oral S-1 with a 24-h infusion of irinotecan plus bevacizumab versus FOLFIRI plus bevacizumab. Methods: The subjects comprised 120 chemotherapy-naïve patients with mCRC. The study group received a 24-h infusion of irinotecan at a dose of 125 mg/m² on days 1 and 15, combined with oral S-1 80 mg/m² on days 1–14 (24h-SIRI/B). The FOLFIRI/B group received irinotecan at a dose of 150 mg/m², 5-fluorouracil given at a dose of 400 mg/m² as a bolus injection and at a dose of 2,400 mg/m² as a 46-h infusion, and 200 mg/m² leucovorin on days 1 and 15. Bevacizumab was given at a dose of 5.0 mg/kg on days 1 and 15 in both groups. Treatment was repeated every 4 weeks. The primary endpoint was 1-year progression-free survival (PFS). Secondary endpoints were PFS, response rates (RR), overall survival (OS), and adverse events (AEs). Results: From December 2013 through January 2018, 120 patients were randomly assigned, 61 patients to the 24h-SIRI/B and 59 patients to the FOLFIRI/B. The median follow-up period was 22.8 months. The 1-year PFS rate was 43.14% in the 24h-SIRI/B arm and 19.15% in the FOLFIRI/B arm (HR = 0.312 [95%CI 0.13–0.78], p = 0.01). The median PFS was 10.2 months (95%CI 8.8–14.3) and 10.0 months (95%CI 7.4–11.0), and the median OS was 29.7 months (95%CI 22.9–43.9) and 28.8 months (95%CI 18.4-ND), respectively (p = 0.3758, p = 0.8234). The overall RR was 86.3 and 61.7%, respectively (p = 0.0053). AEs were similar. Conclusions: Our results show that the 24h-SIRI/B regimen is an effective and reasonably well-tolerated regimen for the first-line treatment of mCRC.