CDK4/6 Inhibitor Dosage Formulations For The Protection Of Hematopoietic Stem And Progenitor Cells During Chemotherapy

摘要

This invention is in the area of dosage formulations and methods of administering a CDK4/6 inhibitor for the transient protection of healthy cells, and in particular hematopoietic stem and progenitor cells (HSPC), from damage associated with DNA damaging chemotherapeutic agents in subjects undergoing DNA damaging chemotherapeutic therapies for the treatment of proliferative disorders. In one aspect, improved protection of healthy cells is disclosed using a dosage that provides desirable pharmacokinetic and pharmacodynamic characteristics, including AUC, Tmax, Cmax, dosage-corrected AUC, and dosage-corrected Cmax. In another aspect, a method of treating a subject undergoing chemotherapy for the treatment of a CDK 4/6-replication independent cellular proliferation disorder by administering Compound 1 is provided.

主权项

1. A method of treating a human subject having small cell lung cancer comprising:
intravenously administering to the subject a composition comprising Compound 1, or an acceptable salt thereof, in a single dose that provides a blood plasma profile mean Cmax (ng/ml) for Compound 1 of between about 1000 (ng/ml) and 3500 (ng/ml), and, subsequently administering to the subject a therapeutically effective amount of at least one chemotherapeutic agent selected from etoposide, carboplatin, topotecan, or a combination thereof,wherein the chemotherapeutic agent is administered to the subject within about four hours or less of the administration of Compound 1.