UGT1A1*28 genotype predicts gastrointestinal toxicity in patients treated with intermediate-dose irinotecan.
Pharmacogenomics
; 10(5): 733-9, 2009 May.
Article
em En
| MEDLINE
| ID: mdl-19450125
ABSTRACT
AIMS:
Variants in UGT1A1 have previously been associated with toxicity from irinotecan chemotherapy. We conducted a pragmatic prospective cohort study to establish the relevance of UGT1A1 variants in the prediction of severe diarrhea and neutropenia in patients with colorectal cancer receiving irinotecan in a routine clinical setting. MATERIALS &METHODS:
Genotyping of UGT1A1*28 and c.-3156G>A was undertaken in an unselected, prospective cohort of 96 individuals treated with irinotecan at a single major UK oncology centre. Data on cytotoxic drugs received, and toxicity for all irinotecan treatment cycles were collected from case notes. Over 95% (92/96) of patients received an intermediate dose of irinotecan (180 mg/m(2), twice weekly). Irinotecan was given in combination with other cytotoxic drugs in 93/96 subjects and Grade 3 or 4 toxicity occurred in 23% of subjects.RESULTS:
No association was found between UGT1A1*28 or c.-3156G>A and neutropenia. However, individuals carrying two copies of UGT1A1*28 (p = 0.04; OR 14; 95% CI 1.1-185) or c.-3156G>A (p = 0.03) had a significantly increased risk of diarrhea over all cycles.CONCLUSION:
Our findings indicate that UGT1A1 genotyping is not a good predictor of hematological toxicity in patients treated with intermediate irinotecan doses. However, it may be useful in the identification of patients at risk of severe diarrhea.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Camptotecina
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Neoplasias Colorretais
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Glucuronosiltransferase
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Trato Gastrointestinal
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Antineoplásicos Fitogênicos
Tipo de estudo:
Etiology_studies
/
Incidence_studies
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Observational_studies
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Prognostic_studies
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Risk_factors_studies
Limite:
Adult
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Aged
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Aged80
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Female
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Humans
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Male
/
Middle aged
Idioma:
En
Revista:
Pharmacogenomics
Assunto da revista:
FARMACOLOGIA
/
GENETICA MEDICA
Ano de publicação:
2009
Tipo de documento:
Article
País de afiliação:
Reino Unido