The present meta analysis of five trials indicates that combination chemotherapy induces its greatest benefit in patients with a good performance status. In these patients, a combination of gem citabine with platinum analogs or fluoropyrimidines induced a statistically significant and also clinically rele vant HR of 0. 76. By contrast, patients with a poor KPS of 60 80% rather seem to have no survival advantage from the more intensive combination chemo therapy. In conclusion, the subgroup analysis of five large rand omized trials provides a possible rationale in favour of combination chemotherapy when applied in good per formance status patients who can tolerate prolonged intensive therapy.
However, post hoc subgroup analyses from single randomized trials can only be regarded as hypothesis generating, and even if there is increasing evi dence for an important prognostic role of performance status, a prospective evaluation of this issue is strongly recommended for future clinical trials in advanced pancreatic cancer. A re evaluation of perform ance status data from all the 15 trials included in this meta analysis even perhaps based on individual patient data would be another promising approach to overcome the limitations of a possible outcome reporting bias. This meta analysis was focused on gemcitabine based chemotherapy combinations and excluded combinations with targeted agents. The results therefore pertain only to the referred chemotherapy doublets. Randomized trials comparing gemcitabine versus gemcitabine plus metallo proteinase inhibitors, tipifarnib or bevacizumab did not show a significant survival benefit.
More promis ing results were obtained from inhibition of GSK-3 the epider mal growth factor receptor by the oral tyrosinekinase inhibitor erlotinib. The combination of gemcitabine with erlotinib induced a significant improve ment of PFS and OS when compared to gemcitabine alone. However, preliminary data from a randomized trial nificant survival benefit for gemcitabine plus cetuximab compared to gemcitabine monotherapy. The question needs to be asked if the results of this meta analysis have an impact on the design of future trials per formed in pancreatic cancer. In conclusion, the following statements can be made 1. One might consider separate treatment strategies for patients with good and poor performance status in future clinical trials.
investigating the EGFR directed antibody cetuximab as a combination partner did not show a sig Meta analysis fluoropyrimidine or otheradvancedgemcitabine cancer overall survival with regard to combination part 2. It has become clear that combination chemotherapy may be a valuable tool to improve treatment efficacy in patients with a good performance status. Further prospec tive exploration of intensive treatment is needed specifi cally in this patient group. 3.