Real-time pharmacokinetics guiding clinical decisions; phase I study of a weekly schedule of liposome encapsulated paclitaxel in patients with solid tumours.
The purpose of this weekly schedule phase I study of liposome encapsulated paclitaxel (LEP) was to define the maximum-tolerated dose (MTD), the recommended dose (RD), the dose-limiting toxicities (DLTs), the pharmacokinetic profiles, and to evaluate preliminarily antitumour effects in patients with refractory solid malignancies. LEP was administered as an intravenous (i.v.) infusion over 45 min once every week for 6 out of 8 weeks. Fourteen patients were treated at doses ranging from 90 to 150 mg/m(2)/week. In one patient, DLT was observed at the dose level of 150 mg/m(2)/week, who received less than 70% of the intended cumulative dose. No cumulative toxicities were observed. Stabilisation of disease for 8 weeks was documented in two patients. The whole blood clearance of total paclitaxel was similar for LEP (15.3+/-8.98 l/h/m(2)) and Taxol (17.5+/-3.43 l/h/m(2)), and the extraliposomal to total drug ratio increased rapidly to unity at later sampling time points. The trial was discontinued upon completion of enrolment of the 150 mg/m(2)/week cohort because an assessment of the pharmacokinetics and clinical data suggested that LEP was unlikely to have any advantages over Taxol. It is concluded that this formulation of LEP is unlikely to provide improvements over the taxanes currently in clinical use.
Department of Medical Oncology, Erasmus University Medical Center-Daniel den Hoed Cancer Center, Groene Hilledijk 301, 3075 EA Rotterdam, PO Box 5201, 3008 AE Rotterdam, The Netherlands. o.soepenberg@erasmusmc.nl
O
O
Soepenberg
A
A
Sparreboom
M J A
MJ
de Jonge
A S Th
AS
Planting
G
G
de Heus
W J
WJ
Loos
C M
CM
Hartman
C
C
Bowden
J
J
Verweij
D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D000972:Antineoplastic Agents, Phytogenic / Q000009:adverse effects / Q000493:pharmacokinetics*; D015331:Cohort Studies; D003657:Decision Making; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006207:Half-Life; D006801:Humans; D007262:Infusions, Intravenous; D008081:Liposomes; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy*; D017239:Paclitaxel / Q000009:adverse effects / Q000493:pharmacokinetics*; D016896:Treatment Outcome
D000972:Antineoplastic Agents, Phytogenic; D008081:Liposomes; D017239:Paclitaxel