Phase I clinical and pharmacokinetic studies of the taxoid derivative RPR 109881A administered as a 1-hour or a 3-hour infusion in patients with advanced solid tumors.

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Serval ID
serval:BIB_25415
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Phase I clinical and pharmacokinetic studies of the taxoid derivative RPR 109881A administered as a 1-hour or a 3-hour infusion in patients with advanced solid tumors.
Journal
Annals of Oncology
Author(s)
Sessa C., Cuvier C., Caldiera S., Bauer J., Van den Bosch S., Monnerat C., Semiond D., Perard D., Lebecq A., Besenval M., Marty M.
ISSN
0923-7534
Publication state
Published
Issued date
2002
Volume
13
Number
7
Pages
1140-1150
Language
english
Abstract
Purpose: To define the maximum tolerated dose (MTD), the recommended phase II dose, the optimal infusion duration and pharmacokinetics of the semisynthetic taxoid derivative RPR 109881 A, given as a 1-h or 3-h infusion every 3 weeks.
Patients and methods: RPR109881A was administered as a 1-h i.v. infusion to 34 patients (study 1) with oral steroids as pre-medication. In a subsequent study, 29 patients were treated at the recommended dose or at the dose immediately below (study 2); the first 14 patients received RPR109881A as a 3-h infusion, while the subsequent 15 were randomized to receive the drug as a 1-h or 3-h infusion. The pharmacokinetics of RPR109881A was studied in plasma and urine and for selected patients in some biological fluids (cerebrospinal fluid, pleural effusion, ascitis).
Results: In study 1, the dose was escalated from 15 to 105 mg/m(2), at which dose two of five patients presented dose-limiting toxicities with febrile neutropenia (FN) after the first cycle, thus defining the MTD. The dose of 90 mg/m(2), at which grade 3/4 neutropenia was almost universal with FN in 18%, was recommended for phase II. At 90 mg/m(2) the incidence of diarrhea, fatigue and alopecia were 59, 29 and 70%, respectively. The results of study 2 were comparable to those of study 1, thus recommending the 1-h infusion duration for phase 11 evaluation. RPR 109881 A exhibited a high total body clearance, a large distribution volume and long terminal half-life of 20 It. RPR 10988 1 A was detected in cerebrospinal fluid shortly after the end of 1-h infusion. Three objective responses were observed in non-small-cell lung cancer (NSCLC) patients, including a patient with brain metastases.
Conclusions: The antitumor activity in NSCLC, the reproducible profile of toxicity and above all the ability to cross the blood-brain barrier make RPR 10988 1 A worthy of further disease-oriented clinical development.
Keywords
Pharmacokinetics, Phase I, Taxanes, Taxoid Derivative, Intravenous-Infusion, Paclitaxel, Cancer, Metabolism
Pubmed
Web of science
Open Access
Yes
Create date
19/11/2007 13:21
Last modification date
01/10/2019 7:17
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