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Phase 1/2 study of cyclin-dependent kinase (CDK)4/6 inhibitor palbociclib (PD-0332991) with bortezomib and dexamethasone in relapsed/refractory multiple myeloma.

TitlePhase 1/2 study of cyclin-dependent kinase (CDK)4/6 inhibitor palbociclib (PD-0332991) with bortezomib and dexamethasone in relapsed/refractory multiple myeloma.
Publication TypeJournal Article
Year of Publication2015
AuthorsNiesvizky R, Badros AZ, Costa LJ, Ely SA, Singhal SB, Stadtmauer EA, Haideri NA, Yacoub A, Hess G, Lentzsch S, Spicka I, Chanan-Khan AA, Raab MS, Tarantolo S, Vij R, Zonder JA, Huang X, Jayabalan D, Di Liberto M, Huang X, Jiang Y, Kim ST, Randolph S, Chen-Kiang S
JournalLeuk Lymphoma
Volume56
Issue12
Pagination3320-8
Date Published2015
ISSN1029-2403
KeywordsAdult, Aged, Aged, 80 and over, Antineoplastic Combined Chemotherapy Protocols, Bortezomib, Cyclin-Dependent Kinase 4, Cyclin-Dependent Kinase 6, Dexamethasone, Drug Administration Schedule, Drug Monitoring, Drug Resistance, Neoplasm, Female, Humans, Kaplan-Meier Estimate, Male, Middle Aged, Multiple Myeloma, Neoplasm Staging, Piperazines, Pyridines, Recurrence, Retreatment, Treatment Outcome
Abstract

This phase 1/2 study was the first to evaluate the safety and efficacy of the cyclin-dependent kinase (CDK) 4/6-specific inhibitor palbociclib (PD-0332991) in sequential combination with bortezomib and dexamethasone in relapsed/refractory multiple myeloma. The recommended phase 2 dose was palbociclib 100 mg orally once daily on days 1-12 of a 21-day cycle with bortezomib 1.0 mg/m2 (intravenous) and dexamethasone 20 mg (orally 30 min pre-bortezomib dosing) on days 8 and 11 (early G1 arrest) and days 15 and 18 (cell cycle resumed). Dose-limiting toxicities were primarily cytopenias; most other treatment-related adverse events were gradeā‰¤3. At a bortezomib dose lower than that in other combination therapy studies, antitumor activity was observed (phase 1). In phase 2, objective responses were achieved in 5 (20%) patients; 11 (44%) achieved stable disease. Biomarker and pharmacodynamic assessments demonstrated that palbociclib inhibited CDK4/6 and the cell cycle initially in most patients.

DOI10.3109/10428194.2015.1030641
Alternate JournalLeuk. Lymphoma
PubMed ID25813205
Grant ListP30 CA016520 / CA / NCI NIH HHS / United States