A total of 317 studies were identified from the database search, of which 51 reports were retrieved for full-text evaluation. Exactly 23 cohorts from 22 trials4,7,9,17–35 met the inclusion criteria and were included in the present systematic review (Figure 1). We only found one phase II RCT that directly compared GEM-based CRT with capecitabine-based CRT. Table 1 shows the characteristics of the included studies. Overall, 843 patients were included, with a median age of 64.7 years (range, 59–68.5 years) for the GEM-based group and 63.1 years (range, 58–67.5 years) for the oral FU group. The median OS was longer in oral FU-based CRT than GEM-based CRT (Table 2), while median radiation dose or median PFS did not differ between groups.
(To view a larger version of Table 1, click here.)
Methodological quality of the included studies was fair; most studies provided adequate outcome ascertainment, enrolled a representative sample of patients, and had an acceptable length of follow-up (Figure 2). However, comparative evidence was at high risk of bias, because we compared data across studies, not within them, and selection bias was likely to be present. Assessment of publication bias was not done because data would be unreliable in view of the few studies included for each treatment group and their high heterogeneity (I2>50%) in most analyses.
Pooled results of primary outcomes
The pooled event rate of OS for S-1-based CRT was significantly higher than that for GEM-based CRT at 1 year (relative risk [RR] 1.27; 95% CI, 1.00–1.65; P=0.03), and at 2 years (RR 1.75; 95% CI, 1.18–2.60; P=0.002; Table 3). ORR and 1-year PFS were not significantly different between S-1 and GEM-based CRT (P=0.06 and P=0.37, respectively). Additionally, comparable efficacy was found between capecitabine and GEM-based CRT in terms of OS, PFS, and ORR (Table 3).
(To view a larger version of Table 3, click here.)
Pooled high-grade acute toxicities
Table 4 shows the overall acute occurrence of high-grade (≥ grade 3) toxic effects with oral FU versus GEM-based CRT. The incidence of high-grade acute hematologic toxicities, nausea, and vomiting was significantly lower in the oral FU-based CRT group than in the GEM-based CRT group (Table 4). Additionally, equivalent frequencies of high-grade diarrhea and fatigue were found between oral FU and GEM-based CRT (P=0.07 and P=0.05, respectively).
(To view a larger version of Table 4, click here.)