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Efficacy of CPX-351, (cytarabine:daunorubicin) liposome injection, against acute lymphoblastic leukemia (ALL) xenograft models of the Pediatric Preclinical Testing Program.

AbstractBACKGROUND:
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:
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.
AuthorsHernan Carol, Mannie M Y Fan, Troy O Harasym, Ingrid Boehm, Lawrence D Mayer, Peter Houghton, Malcolm A Smith, Richard B Lock
JournalPediatric blood & cancer (Pediatr Blood Cancer) Vol. 62 Issue 1 Pg. 65-71 (Jan 2015) ISSN: 1545-5017 [Electronic] United States
PMID25203866 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
Copyright© 2014 Wiley Periodicals, Inc.
Chemical References
  • Liposomes
  • Cytarabine
  • Daunorubicin
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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