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.
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 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.
authors: a Medicine and Hematology/Oncology, Weill Cornell Medical College , New York , NY , USA.
authors: Ruben
authors: R
authors: Niesvizky
authors: b Department of Medicine , University of Maryland Greenebaum Cancer Center , Baltimore , MD , USA.
authors: Ashraf Z
authors: AZ
authors: Badros
authors: c Department of Medicine and UAB-CCC , Bone Marrow Transplantation and Cell Therapy Program, University of Alabama , Birmingham , AL , USA.
authors: Luciano J
authors: LJ
authors: Costa
authors: d Pathology and Laboratory Medicine, Weill Cornell Medical College , New York , NY , USA.
authors: Scott A
authors: SA
authors: Ely
authors: e Division of Hematology/Oncology, Northwestern University Feinberg School of Medicine , Chicago , IL , USA.
authors: Seema B
authors: SB
authors: Singhal
authors: f Division of Hematology/Oncology, University of Pennsylvania Abramson Cancer Center , Philadelphia , PA , USA.
authors: Edward A
authors: EA
authors: Stadtmauer
authors: g Oncology/Hematology and Internal Medicine, Saint Luke's Health System , Kansas City , MO , USA.
authors: Nisreen A
authors: NA
authors: Haideri
authors: h Hematology and Oncology, University of Kansas Medical Center , Kansas City , KS , USA.
authors: Abdulraheem
authors: A
authors: Yacoub
authors: i Department of Hematology , Oncology and Pneumology, University Medical School of the Johannes Gutenberg-University , Mainz , Germany.
authors: Georg
authors: G
authors: Hess
authors: j Division of Hematology/Oncology, Columbia University Medical Center , New York , NY , USA.
authors: Suzanne
authors: S
authors: Lentzsch
authors: k 1st Department of Internal Medicine , Charles University , Praha , Czech Republic.
authors: Ivan
authors: I
authors: Spicka
authors: l Department of Hematology/Oncology , Mayo Clinic , Jacksonville , FL , USA.
authors: Asher A
authors: AA
authors: Chanan-Khan
authors: m Department of Internal Medicine V , University of Heidelberg, and German Cancer Research Center (DFKZ) , Heidelberg , Germany.
authors: Marc S
authors: MS
authors: Raab
authors: n Methodist Hospital and Nebraska Cancer Specialists , Omaha , NE , USA.
authors: Stefano
authors: S
authors: Tarantolo
authors: o Section of BMT and Leukemia, Washington University School of Medicine , St. Louis , MO , USA.
authors: Ravi
authors: R
authors: Vij
authors: p Oncology and Internal Medicine, Karmanos Cancer Institute/Wayne State University , Detroit , MI , USA.
authors: Jeffrey A
authors: JA
authors: Zonder
authors: d Pathology and Laboratory Medicine, Weill Cornell Medical College , New York , NY , USA.
authors: Xiangao
authors: X
authors: Huang
authors: d Pathology and Laboratory Medicine, Weill Cornell Medical College , New York , NY , USA.
authors: David
authors: D
authors: Jayabalan
authors: d Pathology and Laboratory Medicine, Weill Cornell Medical College , New York , NY , USA.
authors: Maurizio
authors: M
authors: Di Liberto
authors: q Pfizer Oncology , San Diego , CA , USA.
authors: Xin
authors: X
authors: Huang
authors: q Pfizer Oncology , San Diego , CA , USA.
authors: Yuqiu
authors: Y
authors: Jiang
authors: q Pfizer Oncology , San Diego , CA , USA.
authors: Sindy T
authors: ST
authors: Kim
authors: q Pfizer Oncology , San Diego , CA , USA.
authors: Sophia
authors: S
authors: Randolph
authors: d Pathology and Laboratory Medicine, Weill Cornell Medical College , New York , NY , USA.
authors: Selina
authors: S
authors: Chen-Kiang
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D000069286:Bortezomib; D051358:Cyclin-Dependent Kinase 4 / Q000037:antagonists & inhibitors; D051361:Cyclin-Dependent Kinase 6 / Q000037:antagonists & inhibitors; D003907:Dexamethasone / Q000008:administration & dosage; D004334:Drug Administration Schedule; D016903:Drug Monitoring; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D009367:Neoplasm Staging; D010879:Piperazines / Q000008:administration & dosage; D011725:Pyridines / Q000008:administration & dosage; D012008:Recurrence; D019233:Retreatment; D016896:Treatment Outcome
chemical_list: D010879:Piperazines; D011725:Pyridines; D000069286:Bortezomib; D003907:Dexamethasone; D051358:Cyclin-Dependent Kinase 4; D051361:Cyclin-Dependent Kinase 6; C500026:palbociclib
keywords: CDK 4/6; Cell cycle; cyclin-dependent kinase 4/6; multiple myeloma; palbociclib