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Cancer Chemotherapy and Pharmacology

, Volume 73, Issue 2, pp 249–257 | Cite as

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
Original Article

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).

Keywords

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

Notes

Acknowledgments

Research reported in this publication was supported by the National Cancer Institute of the National Institutes of Health under Award Number U01CA076576 (PI Michael Grever). CCH was a Paul Calabresi scholar on K12CA133250 from the National Cancer Institute (PI John Byrd). The content is solely the responsibility of the authors and does not represent the official views of the National Cancer Institute or the National Institutes of Health.

Conflict of interest

None of the authors have a relevant conflict of interest to report.

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Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Craig C. Hofmeister
    • 1
  • Ming Poi
    • 2
  • Mindy A. Bowers
    • 3
  • Weiqiang Zhao
    • 4
  • Mitch A. Phelps
    • 5
  • Don M. Benson
    • 1
  • Eric H. Kraut
    • 1
  • Sherif Farag
    • 6
  • Yvonne A. Efebera
    • 1
  • Jennifer Sexton
    • 3
  • Thomas S. Lin
    • 7
  • Michael Grever
    • 1
  • John C. Byrd
    • 1
  1. 1.Division of HematologyThe Ohio State UniversityColumbusUSA
  2. 2.Department of PharmacyThe Ohio State University Comprehensive Cancer CenterColumbusUSA
  3. 3.The Ohio State University Comprehensive Cancer CenterColumbusUSA
  4. 4.Department of Pathology, College of MedicineThe Ohio State UniversityColumbusUSA
  5. 5.College of PharmacyThe Ohio State UniversityColumbusUSA
  6. 6.College of MedicineIndiana University School of MedicineIndianapolisUSA
  7. 7.Oncology Research and DevelopmentGlaxoSmithKlinePhiladelphiaUSA

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