Gemcitabine based combination chemotherapy in advanced pancreatic cancer-indirect comparison

Using the adjusted indirect comparison method proposed by Bucher et al, we have assessed randomised controlled trials of four gemcitabine based combinations namely gemcitabine plus a platinum compound or 5-fluorouracil or irinotecan or capecitabine.No particular combination was significantly superior to another, but the indirect evidence suggests some important trends.The strongest trends on indirect comparison are towards favouring gemcitabine plus capecitabine or gemcitabine plus a platinum compound over gemcitabine plus irinotecan, and to a lesser degree, over gemcitabine plus 5-fluorouracil.We have previously reported a systematic review and meta-analysis of 19 studies evaluating gemcitabine based combination chemotherapy compared to gemcitabine alone [1] in patients with locally advanced and metastatic pancreatic cancer. Overall survival was significantly better for gemcitabine based combination chemotherapy (14 trials 4060 patients HR 0.91; 95% CI 0.85 to 0.97) compared to single agent gemcitabine. A subgroup analysis was performed, dividing the selected studies into four categories defined by the addition to gemcitabine of platinum agents or 5-fluorouracil (5FU) or irinotecan or capecitabine (Table 1). The subgroup analysis found evidence to suggest a survival advantage for gemcitabine combined with either a platinum agent (HR 0.85; 95% CI 0.74 to 0.96) or capecitabine (HR 0.83; 95% CI 0.72 to 0.96), and insufficient evidence to support combinations of gemcitabine with either 5FU (HR 0.98; 95% CI 0.86 to 1.11) or irinotecan (HR 1.01; 95% CI 0.84 to 1.22). These analyses provide estimates of the survival advantage for each combination compared to single agent gemcitabine but do not provide estimates of the survival advantage for each combination compared against another. To date, there is only one phase II randomised controlled trial [2,3] which directly compared different gemcitabine combinations in a head-to-head comparison. This was a small study that direc