2007
DOI: 10.1158/1078-0432.ccr-07-0660
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Predictive Factors of Oxaliplatin Neurotoxicity: The Involvement of the Oxalate Outcome Pathway

Abstract: Purpose: Oxaliplatin displays a frequent dose-limiting neurotoxicity due to its interference with neuron voltage-gated sodium channels through one of its metabolites, oxalate, a calcium chelator. Different clinical approaches failed in neurotoxicity prevention, except calcium-magnesium infusions. We characterized oxalate outcome following oxaliplatin administration and its interference with cations and amino acids. We then looked for genetic predictive factors of oxaliplatininduced neurotoxicity.Experimental D… Show more

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Cited by 111 publications
(74 citation statements)
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References 41 publications
(52 reference statements)
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“…Similar results have been described for GSTP1 in patients with colorectal cancer receiving oxaliplatin-based chemotherapy, 27 but not in others. 28,29 In the current study, 18% of carriers of the GSTP1 GG genotype experienced severe platinum-associated peripheral polyneuropathy. If this is confirmed, then these patients may be candidates for receiving carboplatin instead of cisplatin to avoid severe polyneuropathy.…”
Section: Discussionmentioning
confidence: 47%
“…Similar results have been described for GSTP1 in patients with colorectal cancer receiving oxaliplatin-based chemotherapy, 27 but not in others. 28,29 In the current study, 18% of carriers of the GSTP1 GG genotype experienced severe platinum-associated peripheral polyneuropathy. If this is confirmed, then these patients may be candidates for receiving carboplatin instead of cisplatin to avoid severe polyneuropathy.…”
Section: Discussionmentioning
confidence: 47%
“…90 An important role in the prediction and pathogenesis of oxaliplatin-related neurotoxicity lies with polymorphisms of the gene, AGXT, which codes for the AGXT enzyme responsible for oxalate (which increases drastically after oxaliplatin infusion) metabolism. Patients with the minor haplotype (in contrast to the normal major haplotype) AGXT showed reduced enzymatic activity, higher levels of oxalate and much higher risk of neurotoxicity, both acute and chronic, as was well reported by Gamelin et al 91 Irinotecan Irinotecan (CPT-11 or Campto) is a commonly used cytotoxic drug in colorectal cancer. Irinotecan is a hemisynthetic analog of the natural product, camptothecin, able to inhibit topoisomerase I, a DNA helicase (cutting enzyme).…”
Section: Genetic Alterations In Crcmentioning
confidence: 55%
“…In addition, the GSTP1-105 G allele, could explain higher incidence of severe neurotoxicities, the most common side-effect of oxaliplatin, observed in some patients (Ruzzo et al, 2007). Another polymorphism affecting the AGXT gene coding for the enzyme responsible for the metabolism of oxalate, which peaks during oxaliplatin infusion, could explain higher risk of neurotoxicity in patients (Gamelin et al, 2007).…”
Section: Oxaliplatin: a Metal Precious To The Patientsmentioning
confidence: 99%