TY - JOUR
T1 - Current strategies to minimize toxicity of oxaliplatin
T2 - Selection of pharmacogenomic panel tests
AU - Di Francia, Raffaele
AU - Siesto, Raffaella Stefania
AU - Valente, Daniela
AU - Del Buono, Andrea
AU - Pugliese, Sergio
AU - Cecere, Sabrina
AU - Cavaliere, Carla
AU - Nasti, Guglielmo
AU - Facchini, Gaetano
AU - Berretta, Massimiliano
PY - 2013/11
Y1 - 2013/11
N2 - 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.
AB - 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.
KW - ABCC2
KW - genotyping methods
KW - GSTP1
KW - neurotoxicity
KW - oxaliplatin
KW - pharmacogenomics
UR - http://www.scopus.com/inward/record.url?scp=84885378122&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84885378122&partnerID=8YFLogxK
U2 - 10.1097/CAD.0000000000000002
DO - 10.1097/CAD.0000000000000002
M3 - Article
C2 - 24025562
AN - SCOPUS:84885378122
VL - 24
SP - 1069
EP - 1078
JO - Anti-Cancer Drugs
JF - Anti-Cancer Drugs
SN - 0959-4973
IS - 10
ER -