Schedule-dependent activity of temozolomide plus CPT-11 against a human central nervous system tumor-derived xenograft.
Clin Cancer Res
; 6(10): 4154-7, 2000 Oct.
Article
en En
| MEDLINE
| ID: mdl-11051270
ABSTRACT
Temozolomide, an imidazole tetrazinone, and CPT-11, a camptothecin derivative, have previously been shown to have anti-central nervous system tumor activity in laboratory and clinical studies. The current experiments were designed to evaluate the activity of temozolomide plus CPT-11 against a malignant glioma-derived xenograft, D-54 MG, growing s.c. in athymic nude mice. The initial schedule of i.p. drug administration was temozolomide at 0.1 LD10 on day 1 and CPT-11 at 0.1 LD10 on days 1-5 and 8-14. The combination of these two agents produced greater than additive activity against D-54 MG. This enhanced activity was maintained when the initial administration of CPT-11 was delayed to day 3 or day 5. However, when CPT-11 was administered first on day 1 using 0.5 LD10 (for the single dose schedule) followed by temozolomide (0.1 LD10) 5 h, 3 days, or 5 days later, the enhancement of activity was substantially reduced. These results demonstrate that the combination of temozolomide plus CPT-11 displays a schedule-dependent enhancement of antitumor activity, suggest a mechanistic explanation for the enhanced activity, and provide the rationale for a Phase I trial of this regimen.
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Banco de datos:
MEDLINE
Asunto principal:
Camptotecina
/
Protocolos de Quimioterapia Combinada Antineoplásica
/
Antineoplásicos Alquilantes
/
Dacarbazina
/
Neoplasias del Sistema Nervioso
/
Antineoplásicos Fitogénicos
Límite:
Animals
/
Female
/
Humans
/
Male
Idioma:
En
Revista:
Clin Cancer Res
Asunto de la revista:
NEOPLASIAS
Año:
2000
Tipo del documento:
Article
País de afiliación:
Estados Unidos