Efficacy of CPX-351, (cytarabine:daunorubicin) liposome injection, against acute lymphoblastic leukemia (ALL) xenograft models of the Pediatric Preclinical Testing Program.
Pediatr Blood Cancer
; 62(1): 65-71, 2015 Jan.
Article
em En
| MEDLINE
| ID: mdl-25203866
ABSTRACT
BACKGROUND:
CPX-351, a liposomal formulation of cytarabine and daunorubicin co-encapsulated at an optimized synergistic 51 molar ratio, has demonstrated improved clinical outcomes over conventional cytarabine/daunorubicin treatment in a randomized phase 2 trial in patients with AML as well as superior efficacy against preclinical leukemia models when compared to the free drugs in combination. PROCEDURES Given the promising phase 2 data, limited toxicities observed, and the known clinical activities of cytarabine/daunorubicin, we assessed the efficacy of CPX-351 against a panel of childhood ALL xenograft models. Plasma pharmacokinetics of cytarabine and daunorubicin following CPX-351 treatment were determined by HPLC in order to correlate efficacy with drug exposure.RESULTS:
CPX-351, at a dose of 5 units/kg (corresponding to 5 mg/kg cytarabine and 2.2 mg/kg daunorubicin), was highly efficacious against all xenografts tested, inducing complete responses in four B-lineage xenografts and partial response in one T-lineage xenograft. These therapeutic responses were achieved with CPX-351 doses that provided drug exposures (based on Cmax and AUC) comparable to those observed in patients with AML.CONCLUSIONS:
These results suggest that CPX-351 may be a promising chemotherapeutic to be utilized in the treatment of ALL and support its testing in pediatric patients with leukemia.Palavras-chave
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Protocolos de Quimioterapia Combinada Antineoplásica
/
Leucemia-Linfoma Linfoblástico de Células Precursoras
Tipo de estudo:
Clinical_trials
Limite:
Adolescent
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Animals
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Child
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Child, preschool
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Female
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Humans
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Male
Idioma:
En
Revista:
Pediatr Blood Cancer
Assunto da revista:
HEMATOLOGIA
/
NEOPLASIAS
/
PEDIATRIA
Ano de publicação:
2015
Tipo de documento:
Article
País de afiliação:
Austrália