|Title||Phase 1/2 study of cyclin-dependent kinase (CDK)4/6 inhibitor palbociclib (PD-0332991) with bortezomib and dexamethasone in relapsed/refractory multiple myeloma.|
|Publication Type||Journal Article|
|Year of Publication||2015|
|Authors||Niesvizky 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|
|Keywords||Adult, 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|
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 grade≤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.
|Alternate Journal||Leuk. Lymphoma|
|Grant List||P30 CA016520 / CA / NCI NIH HHS / United States|