Abstract | BACKGROUND:
CPX-351, a liposomal formulation of cytarabine and daunorubicin co-encapsulated at an optimized synergistic 5:1 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: 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.
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Authors | Hernan Carol, Mannie M Y Fan, Troy O Harasym, Ingrid Boehm, Lawrence D Mayer, Peter Houghton, Malcolm A Smith, Richard B Lock |
Journal | Pediatric blood & cancer
(Pediatr Blood Cancer)
Vol. 62
Issue 1
Pg. 65-71
(Jan 2015)
ISSN: 1545-5017 [Electronic] United States |
PMID | 25203866
(Publication Type: Journal Article, Research Support, N.I.H., Extramural)
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Copyright | © 2014 Wiley Periodicals, Inc. |
Chemical References |
- Liposomes
- Cytarabine
- Daunorubicin
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Topics |
- Adolescent
- Animals
- Antineoplastic Combined Chemotherapy Protocols
(administration & dosage, pharmacokinetics, pharmacology)
- Child
- Child, Preschool
- Cytarabine
(administration & dosage)
- Daunorubicin
(administration & dosage)
- Female
- Humans
- Liposomes
- Male
- Maximum Tolerated Dose
- Mice
- Mice, Inbred NOD
- Mice, SCID
- Pediatrics
- Precursor Cell Lymphoblastic Leukemia-Lymphoma
(drug therapy, pathology)
- Tissue Distribution
- Treatment Outcome
- Xenograft Model Antitumor Assays
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