Abstract A135: Evaluation of CPX-351 (cytarabine:daunorubicin) liposome injection efficacy in acute lymphoblastic leukemia (ALL) xenograft models
Notice bibliographique
Résumé
Abstract CPX-351 is a liposome formulation of cytarabine (Cyt) and daunorubicin (Daun) in which the ratio of the two drugs (5:1, mol:mol) maximizes synergy. The marked increase in efficacy observed for CPX-351 vs the free drug cocktail is associated with passive targeting of the synergistic drug ratio to bone marrow where drug-loaded liposomes are preferentially taken up by leukemia cells. Clinical testing of CPX-351 to date has focused on acute myelogenous leukemia (AML), however significant antileukemic activity may also be achievable against ALL. Investigations were undertaken by the Pediatric Preclinical Testing Program (PPTP) of the NCI to provide evidence for CPX-351 treatment-related antileukemic activity against representative pediatric ALL xenograft models. The maximum tolerated dose (MTD) of CPX-351 was established by i.v. dose escalation in non-engrafted NOD/SCID mice with a q2dx3 schedule. Leukemia engraftment was established by i.v. inoculation of either ALL-4 (B-precursor) or ALL-8 (T-lineage) cells into NOD/SCID mice. Drug or vehicle buffer (control) treatment was initiated when the %huCD45+ cells in the peripheral blood was greater than 1% for each cohort. An experimental end-point for each mouse was attained when either the %huCD45+ was greater-than or equal to 25% (an event) or if the mouse reached day 42 without an event. Two measures of antitumor activity were used: 1) an objective response measure (ORM) modeled after the clinical setting; and 2) a time to event measure based on the median event-free survival (EFS) of treated and control animals for each xenograft. Non-engrafted NOD/SCID mice exhibited increased sensitivity to CPX-351 with a corresponding MTD that was roughly 50% of that observed in immune competent mice. Treatment with CPX-351, at a Cyt:Daun dose of 5 units/kg (5 mg/kg Cyt + 2.2 mg/kg Daun), was very effective and yielded objective responses in all evaluable leukemia-bearing mice in both leukemia models. In the ALL-4 model, treatment with CPX-351 induced a median event-free survival (EFS) of 31.0 days (6.8 days for control), which corresponded to a leukemia growth delay (LGD) of 24.2 days (p<0.0001 by logrank test) and resulted in a median ORM score of CR (4CR/3PR). Similar results were obtained in the ALL-8 leukemia model with a median EFS of 32.8 days (10.8 days for controls) and a LGD of 22.0 days (p<0.0001 by logrank test) which resulted in a median ORM score of PR (4PR/3CR). Comparison of drug concentrations observed in the plasma of mice and AML patients after CPX-351 treatment revealed comparable drug exposure in these two settings. CPX-351 exhibits potent antileukemic activity against both a B-cell and T-cell ALL xenograft model at doses that provide clinically relevant plasma drug exposure. Thus, CPX-351 may warrant consideration as a treatment candidate for ALL. (Supported by NCI NO1CM42216) Citation Information: Mol Cancer Ther 2009;8(12 Suppl):A135.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,000 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule tête enseignante, pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».