Primary screening led to the exclusion of 390 articles for the following reasons: reviews (218), other agents/regimens (43), radiotherapy/chemoradiation (99), letters/comments/editorials [26] or case reports [4]. The remaining 372 papers were retrieved for more detailed evaluation. Of these, 144 articles were excluded because selleckbio of adjuvant chemotherapy, 44 for biliary tract cancer, 110 for phase I clinical trials, 38 for not-controlled design and 2 for repeated reports [6,7]. In the end, a total of 35 randomized clinical trials [8-42] were eligible for inclusion in our analysis (Figure (Figure11). Figure 1 Flow chart for trials selection in the meta-analysis. Characteristics of the trials included in the present analysis Thirty-five trials were included in the present analysis, with a total of 9, 979 patients accrued.

Characteristics of the eligible trials are listed in Table Table1.1. Most of the trials (34/35, 97%) evaluated gemcitabine-based chemotherapy for first line or palliative chemotherapy in LA/MPC patients, whereas one trial (Palmer 2007) evaluated neoadjuvant chemotherapy. Twenty-three trials compared single-agent gemcitabine with gemcitabine combined with other cytotoxic agents, nine trials studied gemcitabine monotherapy with gemcitabine plus targeted therapy, and three trials evaluated triplet therapy for LA/MPC patients. Table 1 Characteristics of the eligible trials included in the meta-analysis Among the thirty-five trials, the distribution of baseline patient characteristics was homogeneous. The percentage of patients with metastatic disease ranged from 50% to 91.

1%, while the median age of patients varied from 57.8 to 66 (range: 23-96). The details of chemotherapeutic regimens per arm in each trial are shown in Table Table22. Table 2 Regimens of the trials included in this analysis. Trials comparing single-agent gemcitabine with gemcitabine combined with other cytotoxic agents This analysis evaluated 23 trials (5,577 patients) comparing single-agent gemcitabine with gemcitabine-based Brefeldin_A combinations with other cytotoxic agents. For the primary endpoint of OS, the gemcitabine-based combination therapy was associated with significantly better outcome (ORs, 1.15; 95% CI, 1.03-1.28; p = 0.011) than gemcitabine in monotherapy (Figure (Figure2A).2A). The analysis of PFS also afforded favorable results for the combination arm, with the ORs being 1.27 (95% CI, 1.14-1.42; p < 0.001) (Figure (Figure2B).2B). A similar advantage for gemcitabine-based combinations was observed in terms of the ORR (ORs, 1.58; 95% CI, 1.31-1.91; p < 0.001), with no significant heterogeneity (p = 0.79). Figure 2 Comparison of gemcitabine-X combination with gemcitabine alone. A, OS; B, PFS.