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Abstract
3509 Background: Sensory neurotoxicity (sNT) is the dose-limiting toxicity of oxaliplatin, the integral component of the FOLFOX regimen which has emerged as standard therapy in colorectal cancer. Variations in genes potentially involved in the detoxification (glutathione system: GSTP1, GSTM1) or the cytotoxic mechanism (nucleotide excision repair: ERCC2, XRCC1) of oxaliplatin could serve as genetic predictors of susceptibility to oxaliplatin’s neurotoxic effects. Methods: Germline DNA was extracted from whole blood of 299 patients (pts) who received FOLFOX4 on Intergroup study N9741. Four genetic variants (GSTP1 I105V, GSTM1 del, ERCC2 K751Q, XRCC1 R399Q) were tested for association with the time to development of grade 2/3 sNT and sNT as reason for treatment discontinuation. In addition, pts who developed grade 2 (3) neurotoxicity before a cumulative oxaliplatin dose of 600 (800) mg/m2 was reached were compared to an equal number of pts that tolerated extremely high cumulative doses of oxaliplatin. Resul...
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