Influence of oxaliplatin on 5-fluorouracil plasma clearance and clinical consequences.
Cancer Chemother Pharmacol
; 49(3): 235-43, 2002 Mar.
Article
em En
| MEDLINE
| ID: mdl-11935216
ABSTRACT
UNLABELLED The influence of oxaliplatin (OXA) on 5-fluorouracil (5-FU) plasma clearance was investigated. PATIENTS AND METHODS:
A group of 29 patients with advanced colorectal cancer refractory to prior weekly 8-h 5-FU infusion plus bolus folinic acid (FA), received the same combination plus OXA at 130 mg/m(2) every 3 weeks, OXA plus 5-FU plus FA on day 1, and 5-FU plus FA on days 8 and 15. Steady-state 5-FU concentrations in plasma were measured weekly and 5-FU clearance was calculated. Both before and after the addition of OXA, the 5-FU dose was individually adjusted according to the pharmacokinetic follow-up (target steady-state plasma concentrations 2.5-3 mg/l). RESULTS ANDDISCUSSION:
A total of 122 OXA-containing infusions and 338 5-FU plus FA infusions were given and the median number of infusions per patient was 4 (2-9) and 10 (5-28), respectively. 5-FU plasma clearance was significantly decreased on days 8 and 15 when compared with the value on day 1 and with the values before OXA introduction using a direct paired comparison (2.36 and 2.31 l/min, respectively, vs 3.12 and 3.05 l/min; P<10(-5)). Of 25 evaluable patients, 6 had an objective response after the introduction of OXA (24% objective response rate, 95% confidence interval 9.4-45%).CONCLUSION:
OXA reduces 5-FU plasma clearance for 15 days. This may be a factor in the synergy between the two drugs. It is not linked to dihydropyrimidine dehydrogenase inhibition. Implications for drug schedules in clinical practice are discussed.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Compostos Organoplatínicos
/
Adenocarcinoma
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Protocolos de Quimioterapia Combinada Antineoplásica
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Neoplasias do Colo
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Fluoruracila
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Antineoplásicos
Limite:
Adult
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Aged
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Ano de publicação:
2002
Tipo de documento:
Article