Pharmacokinetics and pharmacogenetics of Gemcitabine as a mainstay in adult and pediatric oncology: an EORTC-PAMM perspective
Open Access
- 23 March 2016
- journal article
- review article
- Published by Springer Nature in Cancer Chemotherapy and Pharmacology
- Vol. 78 (1), 1-12
- https://doi.org/10.1007/s00280-016-3003-0
Abstract
Gemcitabine is an antimetabolite ranking among the most prescribed anticancer drugs worldwide. This nucleoside analog exerts its antiproliferative action after tumoral conversion into active triphosphorylated nucleotides interfering with DNA synthesis and targeting ribonucleotide reductase. Gemcitabine is a mainstay for treating pancreatic and lung cancers, alone or in combination with several cytotoxic drugs (nab-paclitaxel, cisplatin and oxaliplatin), and is an option in a variety of other solid or hematological cancers. Several determinants of response have been identified with gemcitabine, i.e., membrane transporters, activating and inactivating enzymes at the tumor level, or Hedgehog signaling pathway. More recent studies have investigated how germinal genetic polymorphisms affecting cytidine deaminase, the enzyme responsible for the liver disposition of gemcitabine, could act as well as a marker for clinical outcome (i.e., toxicity, efficacy) at the bedside. Besides, constant efforts have been made to develop alternative chemical derivatives or encapsulated forms of gemcitabine, as an attempt to improve its metabolism and pharmacokinetics profile. Overall, gemcitabine is a drug paradigmatic for constant searches of the scientific community to improve its administration through the development of personalized medicine in oncology.Keywords
This publication has 113 references indexed in Scilit:
- Preclinical Absorption, Distribution, Metabolism, and Excretion of an Oral Amide Prodrug of Gemcitabine Designed to Deliver Prolonged Systemic ExposurePharmaceutics, 2013
- Intravesical gemcitabine therapy for non‐muscle invasive bladder cancer (NMIBC): a systematic reviewBJU International, 2012
- Association of Cytidine Deaminase and Xeroderma Pigmentosum Group D Polymorphisms with Response, Toxicity, and Survival in Cisplatin/Gemcitabine-Treated Advanced Non-small Cell Lung Cancer PatientsJournal of Thoracic Oncology, 2011
- Metabolism and accumulation of the lipophilic deoxynucleoside analogs elacytarabine and CP-4126Investigational New Drugs, 2011
- Pharmacokinetics of gemcitabine in non-small-cell lung cancer patients: impact of the 79A>C cytidine deaminase polymorphismEuropean Journal of Clinical Pharmacology, 2010
- Single Nucleotide Polymorphisms of Gemcitabine Metabolic Genes and Pancreatic Cancer Survival and Drug ToxicityClinical Cancer Research, 2010
- Inhibition of Hedgehog Signaling Enhances Delivery of Chemotherapy in a Mouse Model of Pancreatic CancerScience, 2009
- Homozygous CDA*3 is a major cause of life-threatening toxicities in gemcitabine-treated Japanese cancer patientsBritish Journal of Cancer, 2009
- Gemcitabine and Cytosine Arabinoside Cytotoxicity: Association with Lymphoblastoid Cell ExpressionCancer Research, 2008
- Pharmacogenomics of gemcitabine: can genetic studies lead to tailor-made therapy?British Journal of Cancer, 2007