Gemcitabine in combination with 5-fluorouracil with or without folinic acid in the treatment of pancreatic cancer

Abstract

Pancreatic cancer is one of the most frequently reported gastrointestinal tumors and has been reported to have a 5-year survival rate of Ͻ 5%. It is most commonly diagnosed at an advanced stage and until recently, the most frequently administered treatment for patients with advanced disease has been palliative 5-fluoro-

New Therapeutic Directions for Advanced Pancreatic Cancer: Targeting the Epidermal Growth Factor and Vascular Endothelial Growth Factor Pathways

“…The median survival time was 6 weeks longer in the combination arm [17]. The final results of that trial are awaited; however, it should be noted that the addition of 5-FU to gemcitabine [11,18] failed to produce longer survival than with gemcitabine alone in previous randomized trials.…”

A novel biweekly pancreatic cancer treatment schedule with gemcitabine, 5-fluorouracil and folinic acid

“…Chemotherapy has long been considered largely ineffective, but a cautious optimism has recently been expressed since the discovery of new drugs such as gemcitabine (GEM), a fluorinated nucleoside, which used alone or in combination with 5-fluorouracil (5-FU), has been considered effective in terms of antitumour activity and palliation in these patients (Cohen et al, 2002;Heinemann, 2002;Jacobs, 2002;Oettle and Riess, 2002;Evans et al, 2001). Both 5-FU and GEM are fluoropyrimidine prodrugs that need to be converted to cytotoxic metabolites in the tumour cells in order to exert their antitumour activity; several authors have proposed that the two drugs may interact along their respective pathways of activation leading to a synergistic antitumour activity against a number of different malignancies (including pancreatic carcinoma) in vitro and in vivo (Plunkett et al, 1996;Allegra and Grem, 1997;Hidalgo et al, 1997Hidalgo et al, , 1999Berlin et al, 1998 -99;Correale et al, 1999;Schulz et al, 1998;Chu et al, 2001), and for this reason the combination of the two drugs has been investigated in a number of clinical trials in patients with advanced pancreatic carcinoma (Grem, 1996;Hidalgo et al, 1997Hidalgo et al, , 1999Berlin et al, 1998Berlin et al, -99, 2002Cascinu et al, 1999;Correale et al, 2000;Oettle and Riess, 2002).…”

“…Both 5-FU and GEM are fluoropyrimidine prodrugs that need to be converted to cytotoxic metabolites in the tumour cells in order to exert their antitumour activity; several authors have proposed that the two drugs may interact along their respective pathways of activation leading to a synergistic antitumour activity against a number of different malignancies (including pancreatic carcinoma) in vitro and in vivo (Plunkett et al, 1996;Allegra and Grem, 1997;Hidalgo et al, 1997Hidalgo et al, , 1999Berlin et al, 1998 -99;Correale et al, 1999;Schulz et al, 1998;Chu et al, 2001), and for this reason the combination of the two drugs has been investigated in a number of clinical trials in patients with advanced pancreatic carcinoma (Grem, 1996;Hidalgo et al, 1997Hidalgo et al, , 1999Berlin et al, 1998Berlin et al, -99, 2002Cascinu et al, 1999;Correale et al, 2000;Oettle and Riess, 2002). In previous studies of our groups, we demonstrated that GEM affects 5-FU pharmacodynamics (Correale et al, 1999) and pharmacokinetics, (Correale et al, 2003) and determines synergic antitumour activity in vitro (Correale et al, 1999).…”

Up-Regulation of microrna-125b Induced By 5-Fluorouracil (5-FU) Treatment Inhibits Cell Growth and Proliferation in Pancreatic Cancer Cells

“…It is most commonly diagnosed at an advanced stage and the most frequently administered chemotherapeutic compound for patients with advanced disease has been 5-Fluorouracil (5-FU) [1]. 5-FU alone remains one of the standard treatments in advanced pancreatic cancer.…”

“…5-FU alone remains one of the standard treatments in advanced pancreatic cancer. The well-known mechanism of the anti-tumor effects of 5-FU is to inhibit DNA and RNA synthesis [1]. In addition, cell resistance to cytotoxic agents and radiation are two other factors contributing to the poor prognosis of pancreatic cancer [2].…”