Clinical Reversal of Multidrug Resistance.
Oncologist
; 1(4): 269-275, 1996.
Article
en En
| MEDLINE
| ID: mdl-10388001
Reversal of drug resistance offers the hope of increasing the efficacy of conventional chemotherapy. We tested dexverapamil as a P-glycoprotein antagonist in combination with EPOCH chemotherapy in refractory non-Hodgkin's lymphoma. In a cross-over design, dexverapamil was added to EPOCH after disease stabilization or progression occurred. Objective responses were observed in 10 of 41 assessable patients. Biopsies for mdr-1 were obtained before EPOCH treatment and at the time of cross-over to dexverapamil. Levels of mdr-1 were low before EPOCH, but increased fourfold or more in 42% of patients in whom serial samples were obtained. Pharmacokinetic analysis revealed median peak concentrations of dexverapamil and its metabolite, nor-dexverapamil, of 1.66 µmol/l and 1.58 µmol/l, respectively. Since both are comparable antagonists, a median peak total reversing concentration of 3.24 µmol/l was achieved. Pharmacokinetic analysis of doxorubicin and etoposide levels confirmed a delay in the clearance of doxorubicin ranging from 5% to 24%; no change in the pharmacokinetics of etoposide was observed. This study provides sufficient rationale for testing dexverapamil in a randomized clinical trial.
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Colección:
01-internacional
Base de datos:
MEDLINE
Tipo de estudio:
Clinical_trials
Idioma:
En
Revista:
Oncologist
Asunto de la revista:
NEOPLASIAS
Año:
1996
Tipo del documento:
Article
País de afiliación:
Estados Unidos
Pais de publicación:
Reino Unido