Can S-1 replace fluorouracil for advanced gastric cancer? A PRISMA-compliant systematic review and meta-analysis

Abstract

It remains to be seen whether S-1 can be a replacement for infusional fluorouracil (5-FU) for advanced gastric cancer (AGC). The aim of this study was to compare the efficacy and safety of S-1 with 5-FU in AGC.PubMed and Cochrane Library were searched. Randomized controlled trials and meta-analyses comparing S-1 with 5-FU for AGC were eligible. Meta-analysis was performed using RevMan 5.2.Seven trials involving 2443 patients were included. Compared with 5-FU, S-1 showed no significant prolongation of overall survival (OS) (hazard ratio [HR] = 0.91, 95% confidence interval [CI] [0.83–1.01], P = 0.07) and progression-free survival (HR = 0.89, 95% CI [0.70–1.13], P = 0.35), but longer time to treatment failure (HR = 0.74, 95% CI [0.56–0.97], P = 0.03). The objective response rates were comparable (risk ratio [RR] = 1.36, 95% CI [0.95, 1.96], P = 0.10). Regarding treatment-related deaths and hematological toxicities, there was significant heterogeneity between Asian and non-Asian trials, and subgroup analysis was applied. In Asian patients, there was a significant increase in hematological toxicities such as leukopenia (grade 1–4: RR = 1.22, 95% CI [1.08, 1.37], P = 0.001; grade 3–4: RR = 2.21, 95% CI [1.52, 3.21], P < 0.0001), neutropenia (grade 1–4: RR = 1.29, 95% CI [1.11, 1.48], P = 0.0005; grade 3–4: RR = 1.87, 95% CI [1.11, 3.17], P = 0.02), and thrombocytopenia (grade 1–4: RR = 1.71, 95% CI [1.22, 2.41], P = 0.002) in S-1-containing regimens compared with 5-FU-containing regimens, but without significant difference in treatment-related mortality rate (risk difference [RD] = 0.00, 95% CI [−0.01, 0.01], P = 0.68). In non-Asian patients, S-1-containing regimens were, however, associated with significantly fewer treatment-related deaths (RD = −0.02, 95% CI [−0.05, −0.00], P = 0.04), as well as less all grade 1–4 and grade 3–4 hematological toxicities except anemia. There was no significant heterogeneity in nonhematologic toxicities between Asian and non-Asian trials. Lower incidence of grade 1–4 nausea, diarrhea, mucositis, grade 3–4 mucositis, increased creatinine, and decreased calculated creatinine clearance was observed in S-1-containing regimens.S-1 could not improve OS, but increase some hematological toxicities in Asian patients. Therefore, special attention on hematological toxicities should be paid to Asian patients because S-1 is administered on an outpatient basis.

A Rare Case of Reversible Cardiac Dysfunction Associated with Tegafur/Gimeracil/Oteracil (S-1) Therapy

“…9) Moreover, S-1 causes fewer episodes of diarrhea than 5-FU. 10) According to the package insert, the median time required for resolving S-1-induced diarrhea is 9 days. In our patient, diarrhea persisted until after S-1 was discontinued, and grade 3 diarrhea was further observed for 17 days after discontinuation.…”

<p>Comparison of Docetaxel + Oxaliplatin + S-1 vs Oxalipatin + S-1 as Neoadjuvant Chemotherapy for Locally Advanced Gastric Cancer: A Propensity Score Matched Analysis</p>

“…Evidence was also obtained in support of the modified DCF (mDCF) regimens with the substitution of oral 5-FU prodrugs for continuous infusion of 5-FU or the substitution of oxaliplatin for cisplatin. [36][37][38] Moreover, DCF/mDCF was investigated as a NAC for GC in an attempt to enhance the resection rate, which finally resulted in improved survival. [39][40][41] More importantly, encouraging results were witnessed in some unresectable highly advanced GC patients who obtained conversion gastrectomy following the NAC with DCF/DCS.…”

Comparison of efficacy and safety of second-line palliative chemotherapy with paclitaxel plus raltitrexed and paclitaxel alone in patients with metastatic gastric adenocarcinoma: a randomized phase 2 clinical trial

“…Thymidylate synthase is a well-established target enzyme for the therapy of gastric cancers. The mechanism of 5-uorouracil (5FU) resistance was investigated, focusing on the level of thymidylate synthase (TS) ternary complex formed with uoro-deoxyuridine monophosphate (FdUMP) [10,11,12].…”