A phase I trial of flavopiridol in relapsed multiple myeloma

作者：Hofmeister Craig C^*; Poi Ming; Bowers Mindy A; Zhao Weiqiang; Phelps Mitch A; Benson Don M; Kraut Eric H; Farag Sherif; Efebera Yvonne A; Sexton Jennifer; Lin Thomas S; Grever Michael; Byrd John C

来源：Cancer Chemotherapy and Pharmacology, 2014, 73(2): 249-257.

DOI：10.1007/s00280-013-2347-y

• Multiple myeloma
• Flavopiridol
• Cyclin-dependent kinase inhibitor
• Pharmacokinetics
• Phase 1 clinical trial

Flavopiridol is primarily a cyclin-dependent kinase-9 inhibitor, and we performed a dose escalation trial to determine the maximum tolerated dose and safety and generate a pharmacokinetic (PK) profile.
Patients with a diagnosis of relapsed myeloma after at least two prior treatments were included. Flavopiridol was administered as a bolus and then continuous infusion weekly for 4 weeks in a 6-week cycle.
Fifteen patients were treated at three dose levels (30 mg/m(2) bolus, 30 mg/m(2) CIV to 50 mg/m(2) bolus, and 50 mg/m(2) CIV). Cytopenias were significant, and elevated transaminases (grade 4 in 3 patients, grade 3 in 4 patients, and grade 2 in 3 patients) were noted but were transient. Diarrhea (grade 3 in 6 patients and grade 2 in 5 patients) did not lead to hospital admission. There were no confirmed partial responses although one patient with t(4;14) had a decrease in his monoclonal protein > 50 % that did not persist. PK properties were similar to prior publications, and immunohistochemical staining for cyclin D1 and phospho-retinoblastoma did not predict response.
Flavopiridol as a single agent given by bolus and then infusion caused significant diarrhea, cytopenias, and transaminase elevation but only achieved marginal responses in relapsed myeloma (ClinicalTrials.gov identifier NCT00112723).

• 出版日期2014-2