Phase I trial and pharmacokinetics of gemcitabine in children with advanced solid tumors.
J Clin Oncol
; 22(12): 2445-51, 2004 Jun 15.
Article
em En
| MEDLINE
| ID: mdl-15197207
ABSTRACT
PURPOSE:
To determine the maximum tolerated dose, toxicity, and pharmacokinetics of gemcitabine in children with refractory solid tumors. PATIENTS ANDMETHODS:
Gemcitabine was given as a 30-minute infusion for 2 or 3 consecutive weeks every 4 weeks, to 42 patients aged 1 to 21 years. Doses of 1000, 1200 and 1500 mg/m(2) were administered for 3 weeks. Subsequently, gemcitabine was given for only 2 consecutive weeks at 1500, 1800, and 2100 mg/m(2). Plasma concentrations of gemcitabine and its metabolite, 2'2'-difluorodeoxyuridine, were measured in 28 patients.RESULTS:
Forty patients who received 132 courses of gemcitabine were assessable for toxicity. The maximum tolerated dose of gemcitabine given weekly for 3 weeks was 1200 mg/m(2). Dose-limiting toxicity was not seen in one-third of children treated at any doses given for 2 weeks. The major toxicity was myelosuppression in three of five patients at 1500 mg/m(2) for 3 weeks, and one of seven patients at 1800 mg/m(2) for 2 weeks. Other serious adverse events were somnolence, fever and hypotension, and rash in three patients. Gemcitabine plasma concentration-time data were fit to a one- (n = 5) or two-compartment (n = 23) open model. Mean gemcitabine clearance and half-life values were 2140 mL/min/m(2) and 13.7 minutes, respectively. One patient with pancreatic cancer had a partial response. Seven patients had stable disease for 2 to 17 months.CONCLUSION:
Gemcitabine given by 30-minute infusion for 2 or 3 consecutive weeks every 4 weeks was tolerated well by children at doses of 2100 mg/m(2) and 1200 mg/m(2), respectively.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Desoxicitidina
/
Neoplasias
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Antimetabólitos Antineoplásicos
Limite:
Adolescent
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Adult
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Child, preschool
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Female
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Humans
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Male
Idioma:
En
Revista:
J Clin Oncol
Ano de publicação:
2004
Tipo de documento:
Article
País de afiliação:
Estados Unidos