Title:Conventional Chemotherapy of Advanced Pancreatic Cancer
Volume: 13
Issue: 6
Author(s): Francesco Giuliani, Massimo Di Maio, Giuseppe Colucci and Francesco Perrone
Affiliation:
Keywords:
Advanced pancreatic cancer, chemotherapy, gemcitabine, cisplatin, oxaliplatin, DOSE RATE INFUSION, FLUOROPYRIMIDINES, Randomized Trials, PLATINUM SALTS, resistance
Abstract: The vast majority of patients with pancreatic cancer present with locally advanced unresectable or metastatic
disease, and in this setting only a palliative treatment can be offered. Single-agent gemcitabine has been considered the
standard chemotherapy for patients with advanced pancreatic cancer since the results of a pivotal phase III trial showing
superior clinical benefit compared to bolus 5-fluorouracil were published in 1997. In recent years, many randomized trials
have attempted to improve results obtained with gemcitabine exploring a different schedule (fixed dose rate) of its
administration, or testing the addition of one or more drugs to gemcitabine. Unfortunately, none of these trials produced a
statistically significant and clinically relevant improvement in overall survival compared to the standard. A randomized
phase III trial has recently shown a survival advantage using a combination of more drugs (FOLFIRINOX: irinotecan,
oxaliplatin, folinic acid and 5-fluorouracil) compared to single-agent gemcitabine, suggesting that regimens without
gemcitabine can be successfully used in patients with advanced pancreatic cancer. FOLFIRINOX was associated with
worse toxicity than gemcitabine, and the available data suggest that this regimen may be considered for patients with
metastatic pancreatic cancer who are fit enough to withstand potential side effects. The best option for these patients
remains the enrolment in prospective clinical trials. Improvements in the treatment of the advanced disease will possibly
derive from new combinations or from new drugs, but certainly from a better knowledge of the multiple molecular
pathways implicated in pancreatic carcinogenesis and in invasion and metastasis.
