Meta-analyses of chemotherapy for locally advanced and metastatic pancreatic cancer: results of secondary end points analyses

In advanced pancreatic cancer, level one evidence has established a significant survival advantage with chemotherapy, compared to best supportive care. The treatment-associated toxicity needs to be evaluated. This study examines the secondary outcome measures for chemotherapy in advanced pancreatic cancer using meta-analyses. A systematic review was undertaken employing Cochrane methodology, with search of databases, conference proceedings and trial registers. The secondary end points were progression-free survival (PFS)/time to progression (TTP) (summarised using the hazard ratio (HR)), response rate and toxicity ( summarised using relative risk). There was no significant advantage of 5FU combinations vs 5FU alone for TTP ( HR 1.02; 95% CI 0.85-1.23) and toxicity. Progression-free survival (HR 0.78; CI 0.70-0.88), TTP (HR 0.85; 95% CI 0.72 - 0.99) and overall response rate ( RR 0.56; 95% CI 0.46 - 0.68) were significantly better for gemcitabine combination chemotherapy, but offset by the greater grade 3/4 toxicity thrombocytopenia (RR 1.94; 95% CI 1.32-2.84), leucopenia (RR 1.46; 95% CI 1.15-1.86), neutropenia (RR 1.48; 95% CI 1.07-2.05), nausea (RR 1.77; 95% CI 1.37-2.29), vomiting (RR 1.64; 95% CI 1.24-2.16) and diarrhoea (RR 2.73; 95% CI 1.87-3.98). There is no significant advantage on secondary end point analyses for administering 5FU in combination over 5FU alone. There is improved PFS/TTP and response rate, with gemcitabine-based combinations, although this comes with greater toxicity.