Prophylaxis of irinotecan-induced diarrhea with neomycin and potential role for UGT1A1*28 genotype screening: a double-blind, randomized, placebo-controlled study.
Oncologist
; 11(8): 944-54, 2006 Sep.
Article
em En
| MEDLINE
| ID: mdl-16951398
ABSTRACT
OBJECTIVE:
Delayed-type diarrhea is a common side effect of irinotecan and is associated with a bacterial-mediated formation of the active irinotecan metabolite SN-38 from its glucuronide conjugate in the intestine. Based on a pilot study, we hypothesized that concomitant administration of the antibiotic neomycin would diminish exposure of the gut to SN-38 and ameliorate the incidence and severity of diarrhea. PATIENTS ANDMETHODS:
Patients were treated with irinotecan in a multicenter, double-blind, randomized, placebo-controlled trial. Eligible patients received irinotecan (350 mg/m(2) once every 3 weeks) combined with neomycin (660 mg three times daily for three consecutive days, starting 2 days before chemotherapy) or combined with placebo. Blood samples were obtained for additional pharmacokinetic and pharmacogenetic analyses.RESULTS:
Sixty-two patients were evaluable for the toxicity analysis. Baseline patient characteristics, systemic SN-38 exposure, and UGT1A1*28 genotype status (i.e., an additional TA repeat in the promoter region of uridine diphosphate-glucuronosyltransferase isoform 1A1) were similar in both arms. Although distribution, severity, and duration of delayed-type diarrhea did not differ significantly between arms, grade 3 diarrhea tended to be less frequent in the neomycin arm. The presence of at least one UGT1A1*28 allele was strongly related to the incidence of grade 2-3 diarrhea. In the neomycin arm, grade 2 nausea was significantly more common.CONCLUSION:
Our results do not suggest a major role for neomycin as prophylaxis for irinotecan-induced delayed-type diarrhea. It is suggested that the UGT1A1*28 genotype status could be used as a screening tool for a priori prevention of irinotecan-induced delayed-type diarrhea.
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Base de dados:
MEDLINE
Assunto principal:
Neoplasias Gástricas
/
Camptotecina
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Neomicina
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Neoplasias Colorretais
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Glucuronosiltransferase
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Diarreia
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Antibacterianos
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Antineoplásicos Fitogênicos
Tipo de estudo:
Clinical_trials
/
Diagnostic_studies
/
Prognostic_studies
/
Screening_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
Ano de publicação:
2006
Tipo de documento:
Article