A phase I trial of flavopiridol in relapsed multiple myeloma

Cancer Chemother Pharmacol. 2014 Feb;73(2):249-57. doi: 10.1007/s00280-013-2347-y. Epub 2013 Nov 16.


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/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 myeloma (ClinicalTrials.gov identifier NCT00112723).

Publication types

  • Clinical Trial, Phase I
  • Research Support, N.I.H., Extramural

MeSH terms

  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / administration & dosage*
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / blood
  • Antineoplastic Agents / pharmacokinetics
  • Dose-Response Relationship, Drug
  • Flavonoids / administration & dosage*
  • Flavonoids / adverse effects
  • Flavonoids / blood
  • Flavonoids / pharmacokinetics
  • Humans
  • Middle Aged
  • Multiple Myeloma / blood
  • Multiple Myeloma / drug therapy*
  • Multiple Myeloma / metabolism
  • Multiple Myeloma / pathology
  • Piperidines / administration & dosage*
  • Piperidines / adverse effects
  • Piperidines / blood
  • Piperidines / pharmacokinetics
  • Recurrence


  • Antineoplastic Agents
  • Flavonoids
  • Piperidines
  • alvocidib

Associated data

  • ClinicalTrials.gov/NCT00112723