A phase I trial of flavopiridol in relapsed multiple myeloma

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

Research output: Contribution to journalArticle

25 Scopus citations

Abstract

Purpose: 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/m2 bolus, 30 mg/m2 CIV to 50 mg/m2 bolus, and 50 mg/m2 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 myeloma (ClinicalTrials.gov identifier NCT00112723).

Original languageEnglish (US)
Pages (from-to)249-257
Number of pages9
JournalCancer Chemotherapy and Pharmacology
Volume73
Issue number2
DOIs
StatePublished - Feb 2014

Keywords

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

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Pharmacology
  • Pharmacology (medical)
  • Toxicology

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  • Cite this

    Hofmeister, C. C., Poi, M., Bowers, M. A., Zhao, W., Phelps, M. A., Benson, D. M., Kraut, E. H., Farag, S., Efebera, Y. A., Sexton, J., Lin, T. S., Grever, M., & Byrd, J. C. (2014). A phase I trial of flavopiridol in relapsed multiple myeloma. Cancer Chemotherapy and Pharmacology, 73(2), 249-257. https://doi.org/10.1007/s00280-013-2347-y