Activity and Safety of Tegafur, Gimeracil, and Oteracil Potassium for Nasopharyngeal Carcinoma: A Systematic Review and Meta-Analysis

Abstract

In clinical practice, tegafur, gimeracil, and oteracil potassium (S-1) therapy is commonly administered to treat nasopharyngeal carcinoma (NPC). However, its efficacy and safety remain controversial in both randomized controlled trials (RCTs) and non-RCTs. We aimed to evaluate the efficacy and safety of S-1 treatment for NPC. We searched PubMed, Ovid, EMBASE, the Cochrane Library, China National Knowledge Infrastructure, Wanfang Database, and VIP databases for RCTs of chemotherapy with or without S-1 for NPC, from 2001 to 2020. A meta-analysis was performed using RevMan5.3 and Stata15. Randomized controlled trials published in journals were included irrespective of blinding and language used. Patients were diagnosed with NPC through a clinicopathological examination; patients of all cancer stages and ages were included. Overall, 25 trials and 1858 patients were included. There were significant differences in the complete remission (OR = 2.42, 95% CI (1.88-3.10), P < 0.05) and overall response rate (OR = 2.68, 95% CI (2.08-3.45), P < 0.05) between the S-1 and non-S-1 groups. However, there was no significant difference in partial remission (OR = 1.10, 95% CI (0.87-1.39), P=0.42) and seven adverse reactions (leukopenia, thrombocytopenia, nausea and vomiting, diarrhea, dermatitis, oral mucositis, and anemia) between the S-1 and non-S-1 groups. Additionally, statistical analyses with six subgroups were performed. S-1 was found to be a satisfactory chemotherapeutic agent combined with radiotherapy, intravenous chemotherapy, or chemoradiotherapy for NPC. As an oral medicine, the adverse reactions of S-1, especially gastrointestinal reactions, can be tolerated by patients, thereby optimizing their quality of life. S-1 may be a better choice for the treatment of NPC. This trial is registered with CRD42019122041.

Figure 1

PRISMA flow diagram of literature screening.

Figure 2

Forest plots of the comparison between the experimental (S-1 treatment) and control (non-S-1 treatment) groups in terms of (a) complete remission (CR), (b) partial remission (PR), and (c) response rate (RR).

Figure 3

Forest plots of the comparison of adverse reactions between the experimental (S-1 treatment) and control (non-S-1 treatment) groups. (a) Leukopenia, (b) thrombocytopenia, (c) nausea and vomiting, (d) gastrointestinal reactions, (e) diarrhea, (f) oral mucositis, (g) dermatitis, and (h) anemia.

Figure 4

Forest plots of the comparison between S-1 treatment and non-S-1 treatment in the subgroups: (a) locally advanced NPC RR, (b) advanced NPC RR, (c) chemotherapy RR, (d) RC vs R RR, (e) RC RR, and (f) S-1 vs. 5-Fu RR. RR, response rate; chemotherapy, treatment of the experimental and control groups with chemotherapy; RC vs. R, chemotherapy concomitant with radiotherapy (S-1 treatment) and radiotherapy alone (non-S-1 treatment); RC, treatment of the experimental and control groups with chemoradiotherapy; 5-Fu, 5-fluorouracil; S-1 vs. 5-Fu, treatment of the experimental group with S-1 and the control group with 5-Fu.

Figure 5

Sensitivity analysis of the primary outcomes: (a) complete remission, (b) partial remission, and (c) response rate. Funnel plot analysis: Begg's test for (d) complete remission and (e) response rate. (f) Trim-and-fill method for complete remission.