Title
Pharmacokinetics of carboplatin with and without amifostine in patients with solid tumors
Author
Korst, A.E.C.
van der Sterre, M.L.T.
Eeltink, C.M.
Fichtinger-Schepman, A.M.J.
Vermorken, J.B.
van der Vijgh, W.J.F.
Centraal Instituut voor Voedingsonderzoek TNO
Publication year
1997
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 pmol/l·h versus 280 ± 62 μmol/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.
Subject
Pharmacology
Amifostine
Carboplatin
Adult
Blood sampling
Clinical article
Clinical trial
Controlled clinical trial
Creatinine blood level
Creatinine clearance
Drug blood level
Drug efficacy
Drug half life
Enzyme linked immunosorbent assay
Female
Human
Intravenous drug administration
Male
Phase 1 clinical trial
Solid tumor
Amifostine
Animals
Antineoplastic Agents
Carboplatin
Dose-Response Relationship, Drug
Half-Life
Kidney
Kidney Function Tests
Metabolic Clearance Rate
Mice
Mice, Nude
Neoplasms
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http://resolver.tudelft.nl/uuid:1a55d44f-337e-49f0-a17e-2f11bffb6a27
TNO identifier
233891
ISSN
1078-0432
Source
Clinical Cancer Research, 3 (5), 697-703
Document type
article