title: Developments in metastatic pancreatic cancer: is gemcitabine still the standard?
abstract: In the past 15 years, we have seen few therapeutic advances for patients with pancreatic cancer, which is the fourth leading cause of cancer-related death in the United States. Currently, only about 6% of patients with advanced disease respond to standard gemcitabine therapy, and median survival is only about 6 mo. Moreover, phase III trials have shown that adding various cytotoxic and targeted chemotherapeutic agents to gemcitabine has failed to improve overall survival, except in cases in which gemcitabine combined with erlotinib show minimal survival benefit. Several meta-analyses have shown that the combination of gemcitabine with either a platinum analog or capecitabine may lead to clinically relevant survival prolongation, especially for patients with good performance status. Meanwhile, many studies have focused on the pharmacokinetic modulation of gemcitabine by fixed-dose administration, and metabolic or transport enzymes related to the response and toxicity of gemcitabine. Strikingly, a phase III trial in 2010 showed that, in comparison to gemcitabine alone, the FOLFIRINOX regimen in patients with advanced disease and good performance status, produced better median overall survival, median progression-free survival, and objective response rates. This regimen also resulted in greater, albeit manageable toxicity.
authors.affiliation: Jie-Er Ying, Li-Ming Zhu, Bi-Xia Liu, Department of Medical Oncology, Zhejiang Cancer Hospital, Hangzhou 310022, Zhejiang Province, China. jieerying@yahoo.cn
authors.forename: Jie-Er
authors.initials: JE
authors.lastname: Ying
authors.forename: Li-Ming
authors.initials: LM
authors.lastname: Zhu
authors.forename: Bi-Xia
authors.initials: BX
authors.lastname: Liu
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001557:Benzenesulfonates / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D018572:Disease-Free Survival; D000069347:Erlotinib Hydrochloride; D006801:Humans; D015201:Meta-Analysis as Topic; D009362:Neoplasm Metastasis / Q000473:pathology*; D009536:Niacinamide / Q000031:analogs & derivatives; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D011725:Pyridines / Q000627:therapeutic use; D011799:Quinazolines / Q000627:therapeutic use; D000077157:Sorafenib; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; D001557:Benzenesulfonates; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors; D011725:Pyridines; D011799:Quinazolines; D003841:Deoxycytidine; D009536:Niacinamide; D000077157:Sorafenib; D000069347:Erlotinib Hydrochloride; D000093542:Gemcitabine