Thirty-five trials (9,979 participants) were included in the review. Sample sizes ranged from 40 to 824. The reviewers did not publish the results of the quality assessment. Length of follow-up was unclear. Numbers of patients lost to follow-up were unclear.
Significant benefits were observed with gemcitabine combination therapy with cytotoxic agents (23 trials, 5,577 participants) compared to single-agent gemcitabine in overall survival (OR 1.15, 95% CI 1.03 to 1.28) and progression-free survival (OR 1.27, 95% CI 1.14 to 1.42).
Statistically significant benefits were observed for overall survival (OR 1.33, 95% CI 1.08 to 1.64) and progression-free survival (OR 1.53, 95% CI 1.24 to 1.88) when gemcitabine was combined with fluoropyrimidine and compared to gemcitabine monotherapy (six trials, n=1829). Both oral capecitabine and infused 5-fluorouracil were used in fluoropyrimidine treatment.
Analysis of gemcitabine-oxaliplatin combinations found significant benefits in overall survival (OR 1.33, 95% CI 1.05 to 1.69; three trials, 900 participants) and progression-free survival (OR 1.38, 95% CI 1.08 to 1.76; two trials, 840 participants) compared to gemcitabine monotherapy. There were no significant differences in overall survival (six trials, 873 participants) and progression-free survival (four trials, 785 participants) when gemcitabine-cisplatin combinations were compared to gemcitabine monotherapy.
One trial in which gemcitabine-cisplatin was administered in the neoadjuvant setting was evaluated. This combination was associated with improved survival at 12 months (62% for combination therapy and 42% for gemcitabine monotherapy).
The combination of gemcitabine and camptothecin (four trials, 839 participants) improved overall response rates (OR 2.03, 95% CI 1.28 to 3.23). No benefits in overall or progression-free survival were observed compared to gemcitabine monotherapy.
Visual appraisal of funnel plots revealed no evidence of publication bias.