1% v 12.4%; p = 0.034) and PFS (hazard ratio, 0.78; 95% CI, 0.66 to 0.93; p = 0.004) and was associated with a trend toward improved OS (hazard ratio, 0.86; 95% CI, 0.72 to 1.02; p = 0.08) compared with gemcitabine alone. On the basis of these results, he recommended http://www.selleckchem.com/products/Perifosine.html that gemcitabine/capecitabine should be considered one of the standard first-line options in LA/MPC. In 1993, Wils [49] was the first to report that single-agent cisplatin has therapeutic activity in LA/MPC with an ORR of 21%. Soon afterwards, several phase II studies discussed the gemcitabine plus cisplatin combination in a variety of schedules. Adding cisplatin to gemcitabine appeared to be very active, with ORR ranging from 9% to 31% and median OS from 5.6 to 9.6 months in these phase II trials [50-52].

Furthermore, in the neoadjuvant setting, Palmer (2007) showed that combination therapy with gemcitabine and cisplatin was associated with a high resection rate and an encouraging survival rate. However, the pooled analysis showed that the PFS and ORR achieved with the gemcitabine and platinum combination were significantly greater than those achieved with gemcitabine monotherapy; however, no statistically significant difference between the 2 treatment approaches were observed in the case of OS. This result was consistent with that obtained in a study conducted by Bria [4]. In Bria’s meta-analysis, platinum combinations led to the greater absolute benefits in terms of PFS and ORR as compared with single-agent gemcitabine (10% and 6.5%, respectively), but did not result in an OS benefit.

However, Heinemann [45] reported contrary results, with a ORs of 0.85 (p = 0.010) for platinum-gemcitabine combinations compared to gemcitabine alone. Heinemann’s study included 15 trials with 4465 patients, whereas Bria’s study included 20 trials with 6296 patients; our study included 35 trials with 9979 patients. The greater number of included trials and case load in our study may have contributed to the more favorable results obtained in our study. Further, our subgroup analysis showed that the OS (p = 0.019), PFS (p = 0.011), and one-year survival (p = 0.04) in the gemcitabine-oxaliplatin group were significantly better than those in the gemcitabine monotherapy group. On the contrary, the comparison of gemcitabine-cisplatin with gemcitabine alone showed that there was no survival benefit (OS: p = 0.

93; PFS: p = 0.17) with the former. Hence, we concluded that the combination of gemcitabine Brefeldin_A and oxaliplatin is superior to gemcitabine plus cisplatin and may be recommended as one of the standard first-line therapies for LA/MPC. The third key finding was that the combination of gemcitabine plus other cytotoxic agents showed disappointing results. According to the literature, the combination of gemcitabine and irinotecan resulted in an objective response of 25% with a median OS ranging from 5.7 to 7 months (Rocha-Lima 2002, Stathopoulos 2004).