Hofmeister, Craig C.Poi, MingBowers, Mindy A.Zhao, WeiqiangPhelps, Mitch A.Benson, Don M.Kraut, Eric H.Farag, SherifEfebera, Yvonne A.Sexton, JenniferLin, Thomas S.Grever, MichaelByrd, John C.2016-01-152016-01-152014-02Hofmeister, C. C., Poi, M., Bowers, M. A., Zhao, W., Phelps, M. A., Benson, D. M., … Byrd, J. C. (2014). A phase I trial of Flavopiridol in relapsed multiple myeloma. Cancer Chemotherapy and Pharmacology, 73(2), 249–257. http://doi.org/10.1007/s00280-013-2347-yhttps://hdl.handle.net/1805/8069PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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 myelomaen-USPublisher PolicyMultiple myelomaFlavopiridolArticle