Pharmacokinetics of carboplatin with and without amifostine in patients with solid tumors.
Clin Cancer Res
; 3(5): 697-703, 1997 May.
Article
em En
| MEDLINE
| ID: mdl-9815738
ABSTRACT
We showed previously that amifostine (WR 2721; Ethyol), a protector against carboplatin-induced toxicities, changed the pharmacokinetics of carboplatin in tumor-bearing nude mice. In the present study, the influence of amifostine on the pharmacokinetics of carboplatin was studied in patients when carboplatin was given in combination with three doses of amifostine, administered just before the carboplatin infusion and 2-4 h thereafter. Compared with a control group of patients who received carboplatin alone, the patients receiving the combination had a longer final half-life of ultrafilterable platinum species [5.0 h versus 3.5 h in patients with a normal creatinine clearance (Clcr > 80 ml/min); 5.6 h versus 4.2 h in those with an impaired renal function (50 < Clcr < 80 ml/min)]. This might be caused by an influence of amifostine on the renal clearance of carboplatin as suggested by a transient increase in serum creatinine levels 24 h after treatment in the patients receiving the combination (mean +/- SD 34.1% +/- 17.2% versus -1.8% +/- 16.5% in patients treated with carboplatin alone). The impact of these changes on the area under the concentration-time curves of the ultrafilterable platinum species was hardly noticeable in patients with a normal renal function but led to a significant increase in patients with an impaired renal function (395 +/- 59 micromol/l.h versus 280 +/- 62 micromol/l.h in patients receiving carboplatin alone). The clinical relevance of this influence is unclear, although theoretically it may result in an increase in the efficacy of carboplatin, as has been observed in tumor-bearing nude mice.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Carboplatina
/
Amifostina
/
Neoplasias
/
Antineoplásicos
Limite:
Animals
Idioma:
En
Revista:
Clin Cancer Res
Ano de publicação:
1997
Tipo de documento:
Article