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/m 2 on days 1 and 15, combined with oral S-1 80 mg/m 2 on days 1-14 (24h-SIRI/B). The FOLFIRI/B group received irinotecan at a dose of 150 mg/m 2 , 5-fluorouracil given at a dose of 400 mg/m 2 as a bolus injection and at a dose of 2,400 mg/m 2 as a 46-h infusion, and 200 mg/m 2 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 welltolerated regimen for the first-line treatment of mCRC.

Efficacy of Bevacizumab and Gemcitabine in Combination with Cisplatin in the Treatment of Esophageal Cancer and the Effect on the Incidence of Adverse Reactions

“…As the most potent proangiogenic factor known, vigorous expression of VEGF is observed in tumor patients [ 20 , 21 ]. In the current study, the VEGF levels were reduced in both groups after treatment, with significantly lower levels in the study group than in the control group ( P < 0.05), which was similar to the findings of Sadahiro et al [ 22 ], suggesting that bevacizumab and gemcitabine combined with cisplatin for esophageal cancer could reduce VEGF levels and promote apoptosis of cancer cells. Cyfra21-1 is a marker of epithelial cell carcinogenesis that exists in the plasma as an oligomer, which is proteolytically cleaved and enters the circulation upon cell carcinogenesis [ 23 ].…”

Systematic review and non-inferiority meta-analysis of randomised phase II/III trials on S-1-based therapy versus 5-fluorouracil- or capecitabine-based therapy in the treatment of patients with metastatic colorectal cancer

“…An overview of studies and median PFS data are presented in Appendix A5. Except for the study by Kim et al [19], which reported a median time to progression of 7.4 months for the control arm versus 6.1 months for the S-1-based arm, the other three studies reported a comparable time to progression with differences ranging from 0.2 to 0.7 months [21,22,24]. All four studies reported no statistically significant difference in PFS between 5-FU/ capecitabine-based versus S-1-based therapy (P > 0.05).…”

“…For the primary outcome, five studies were rated as low risk of bias [10,16,19,20,26], whereas five other studies were rated as some concerns for risk of bias because of concerns arising from the randomisation process [22,24], missing outcome data [21], measurement of the outcome [25,27] and/or selection of the reported results [21,22] (Appendix A3). Visual inspection of the funnel plots indicated no apparent asymmetry, and therefore, we assume a low risk of publication bias (Appendix A4).…”

“…In addition, median PFS (months) per arm was reported by four other studies: three first-line studies [19,21,22] and one second-line study [24]. An overview of studies and median PFS data are presented in Appendix A5.…”

“…We were able to extract treatment-related toxicity data from five studies that investigated oxaliplatin-containing S-1 combination therapy [19,20,24e26] and three studies that investigated irinotecan-containing S-1 combination therapy [21,22,27].…”