Progression-free survival

All studies21–26 including 1,794 patients reported HR for PFS. We also assessed the effect on PFS (summarized in Figure 3), and found that COX-2 inhibitors plus chemotherapy did not significantly differ from chemotherapy alone (HR =0.97, 95% CI: 0.86–1.10, I2=0.0%, P=0.849). As previously mentioned, we also performed two subgroup analyses. However, no significant differences were obtained in the following groups: celecoxib (HR =0.96, 95% CI: 0.83–1.12, I2=0.0%, P=0.584), rofecoxib (HR =1.00, 95% CI: 0.76–1.31, I2=NA, P=NA), apricoxib (HR =0.97, 95% CI: 0.58–1.62, I2=NA, P=NA), first-line treatment (HR =0.97, 95% CI: 0.84–1.11, I2=0.0%, P=0.578), or second-line treatment (HR =0.99, 95% CI: 0.74–1.33, I2=0.0%, P=0.924).


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(To view a larger version of Figure 3, click here.)

One-year survival rate

Five RCTs including 1,482 patients reported 1-year mortality rate figures. We next evaluated the effect on 1-year SR (summarized in Figure 4). COX-2 inhibitors plus chemotherapy did not significantly differ from chemotherapy alone (RR =1.03, 95% CI: 0.89–1.20, I2=0.0%, P=0.531). Moreover, when grouped by the type of COX-2 inhibitors, subgroup analysis also did not yield significant results: celecoxib (RR =1.03, 95% CI: 0.86–1.22, I2=36.3%, P=0.208), rofecoxib (RR =1.06, 95% CI: 0.78–1.44, I2=NA, P=NA), or apricoxib (RR =1.00, 95% CI: 0.15–6.72, I2=NA, P=NA). Similar results were found in the subgroup analysis according to treatment line: first-line treatment (RR =1.08, 95% CI: 0.92–1.27, I2=0.0%, P=0.958) and second-line treatment (RR =0.68, 95% CI: 0.41–1.14, I2=0.0%, P=0.676).

(To view a larger version of Figure 4, click here.)

Overall response rate

Four RCTs including 1,410 patients reported ORR. When evaluating the effect on ORR (summarized in Figure 5), COX-2 inhibitors combined with chemotherapy were found to be more effective than chemotherapy alone (RR =1.25, 95% CI: 1.06–1.48, I2=0.0%, P=0.420). To better assess the efficacy of COX-2 inhibitors for advanced NSCLC, we also conducted further subgroup analysis. Significantly increased ORRs were observed for rofecoxib (RR =1.56, 95% CI: 1.08–2.25, I2=NA, P=NA) and first-line treatment (RR =1.27, 95% CI: 1.07–1.50, I2=0.0%, P=0.451). Whereas celecoxib (RR =1.18, 95% CI: 0.98–1.42, I2=0.0%, P=0.562) and second-line treatment with COX-2 inhibitors for patients with advanced NSCLC showed no significant difference (RR =0.49, 95% CI: 0.09–2.60, I2=NA, P=NA).

(To view a larger version of Figure 5, click here.)

Toxicities

Finally, we assessed the toxicities of COX-2 inhibitors plus chemotherapy for patients with advanced NSCLC. Results indicated that grade 3 and grade 4 toxicities of leukopenia, thrombocytopenia, and cardiovascular events increased with the addition of COX-2 inhibitors: leukopenia (RR =1.21, 95% CI: 1.03–1.42, I2=0.0%, P=0.499), thrombocytopenia (RR =1.32, 95% CI: 1.04–1.67, I2=0.0%, P=0.560), and cardiotoxicity (RR =2.39, 95% CI: 1.06–5.42, I2=0.0%, P=0.690). However, significantly increased risks of other toxicities (anemia, nausea/vomiting, diarrhea, asthenia) and grade 3 and grade 4 effects of treatment were not found. Detailed data are listed in Table 3.

(To view a larger version of Table 3, click here.)