title: Current strategies to minimize toxicity of oxaliplatin: selection of pharmacogenomic panel tests.
abstract: Oxaliplatin is an anticancer drug routinely used to treat colorectal, gastroesophageal, ovarian, breast, head/neck, and genitourinary cancers. Discontinuation of oxaliplatin treatment is mostly because of peripheral neuropathy, more often than for tumor progression, potentially compromising patient benefit. Several strategies to prevent neurotoxicity have so far been investigated. To overcome this life-threatening side effect, while taking advantage of the antineoplastic activities of oxaliplatin, we describe in detail recent findings on the underlying mechanisms of genetic variants associated with toxicity and resistance to oxaliplatin-based chemotherapy in colorectal cancer. A comprehensive panel of eight polymorphisms, previously validated as significant markers related to oxaliplatin toxicity, is proposed and discussed. In addition, the most common available strategies or methods to prevent/minimize the toxicity were described in detail. Moreover, an early outline evaluation of the genotyping costs and methods was taken in consideration. With the availability of individual pharmacogenomic profiles, the oncologists will have new means to make treatment decisions for their patients that maximize benefit and minimize toxicity. With this purpose in mind, the clinician and lab manager should cooperate to evaluate the advantages and limitations, in terms of costs and applicability, of the most appropriate pharmacogenomic tests for routine incorporation into clinical practice.
authors.affiliation: aHematology-Oncology and Stem Cell Transplantation Unit bUro-Gynaecologic Department cAbdominal Department, Medical Oncology Unit, National Cancer Institute, Fondazione 'G. Pascale' IRCCS dItalian Association of Pharmacogenomics and Molecular Diagnostics eMMG ASL CE1, Medicina del Lavoro fCETAC Research Center, Caserta gDepartment of Medical Oncology, CRO National Cancer Institute, Aviano (PN), Italy.
authors.forename: Raffaele
authors.initials: R
authors.lastname: Di Francia
authors.forename: Raffaella Stefania
authors.initials: RS
authors.lastname: Siesto
authors.forename: Daniela
authors.initials: D
authors.lastname: Valente
authors.forename: Andrea
authors.initials: A
authors.lastname: Del Buono
authors.forename: Sergio
authors.initials: S
authors.lastname: Pugliese
authors.forename: Sabrina
authors.initials: S
authors.lastname: Cecere
authors.forename: Carla
authors.initials: C
authors.lastname: Cavaliere
authors.forename: Guglielmo
authors.initials: G
authors.lastname: Nasti
authors.forename: Gaetano
authors.initials: G
authors.lastname: Facchini
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Berretta
mesh_terms: D000970:Antineoplastic Agents / Q000493:pharmacokinetics / Q000633:toxicity*; D004334:Drug Administration Schedule; D006801:Humans; D020258:Neurotoxicity Syndromes / Q000201:enzymology / Q000209:etiology / Q000235:genetics* / Q000517:prevention & control*; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity*; D000077150:Oxaliplatin; D010597:Pharmacogenetics / Q000379:methods*; D011110:Polymorphism, Genetic; D016032:Randomized Controlled Trials as Topic
chemical_list: D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin