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

Abstract

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 ¼ 1.02; 95% CI ¼ 0.85 -1.23) and toxicity. Progression-free survival (HR 0.78; CI 0.70 -0.88), TTP (HR ¼ 0.85; 95% CI ¼ 0.72 -0.99) and overall response rate (RR ¼ 0.56; 95% CI ¼ 0.46 -0.68) were significantly better for gemcitabine combination chemotherapy, but offset by the greater grade 3/4 toxicity thrombocytopenia (RR ¼ 1.94; 95% CI ¼ 1.32 -2.84), leucopenia (RR ¼ 1.46; 95% CI ¼ 1.15 -1.86), neutropenia (RR ¼ 1.48; 95% CI ¼ 1.07 -2.05), nausea (RR ¼ 1.77; 95% CI ¼ 1.37 -2.29), vomiting (RR ¼ 1.64; 95% CI ¼ 1.24 -2.16) and diarrhoea (RR ¼ 2.73; 95% CI ¼ 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.

Gemcitabine and capecitabine with or without telomerase peptide vaccine GV1001 in patients with locally advanced or metastatic pancreatic cancer (TeloVac): an open-label, randomised, phase 3 trial

“…37 The reviews showed that chemoradiation followed by chemotherapy did not demonstrate any survival advantage over chemotherapy alone. There was a significant survival benefit for chemotherapy over best supportive care and gemcitabine combinations over gemcitabine alone including gemcitabine with capecitabine.…”

“…The combination of gemcitabine with capecitabine was chosen as this could potentiate the vaccine effects and was also associated with significantly improved objective responses compared to gemcitabine alone. 22,37,38 Interpretation This is one of the largest randomized clinical trials ever undertaken in pancreatic cancer and the largest trial of vaccine therapy ever undertaken in any solid cancer type. There was no survival benefit from the addition of the GV1001 vaccine to gemcitabine and capecitabine in patients with advanced pancreatic cancer.…”

KL1 Internal Repeat Mediates Klotho Tumor Suppressor Activities and Inhibits bFGF and IGF-I Signaling in Pancreatic Cancer

“…5-FU and gemcitabine are chemotherapeutic drugs commonly used for the treatment of pancreatic cancer (28). The ability of klotho to enhance their activity on pancreatic cancer cells was examined.…”

Randomized trials in exocrine pancreatic cancer

“…Istnieje przynajmniej 8 metaanaliz dotyczących terapii łączonej z zastosowaniem gemcytabiny [68][69][70][71][72][73][74][75]. Wszystkie razem potwierdzają fakt, że gemcytabina jest nadal złotym standardem w terapii zaawansowanego raka trzustki, a terapia skojarzona przynosi pewne korzyści, lecz w porównaniu z monoterapią zwiększa odsetek działań niepożądanych oraz koszty.…”