Can S-1 replace fluorouracil for advanced gastric cancer? A PRISMA-compliant systematic review and meta-analysis.
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.
Division of Gastrointestinal Surgery, Department of Surgical Oncology, Sichuan Cancer Hospital and Institute, Chengdu, Sichuan Province, PR China Department of Geriatrics, Sichuan University West China Hospital, Chengdu, Sichuan Province, PR China.
Xiao-Dong
XD
Chen
Fu-Qian
FQ
He
Mi
M
Chen
Ling-Chao
LC
Tang
Xiao-Li
XL
Tang
D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use; D004338:Drug Combinations; D005472:Fluorouracil / Q000627:therapeutic use*; D006801:Humans; D009367:Neoplasm Staging; D010094:Oxonic Acid / Q000627:therapeutic use*; D011379:Prognosis; D013274:Stomach Neoplasms / Q000175:diagnosis / Q000188:drug therapy*; D005641:Tegafur / Q000627:therapeutic use*
D000964:Antimetabolites, Antineoplastic; D004338:Drug Combinations; C079198:S 1 (combination); D005641:Tegafur; D010094:Oxonic Acid; D005472:Fluorouracil