A phase I trial of flavopiridol in relapsed multiple myeloma.

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).
AuthorsCraig 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
JournalCancer chemotherapy and pharmacology (Cancer Chemother Pharmacol) Vol. 73 Issue 2 Pg. 249-57 (Feb 2014) ISSN: 1432-0843 [Electronic] Germany
PMID24241210 (Publication Type: Clinical Trial, Phase I, Journal Article, Research Support, N.I.H., Extramural)
Chemical References
  • Antineoplastic Agents
  • Flavonoids
  • Piperidines
  • alvocidib
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents (administration & dosage, adverse effects, blood, pharmacokinetics)
  • Dose-Response Relationship, Drug
  • Flavonoids (administration & dosage, adverse effects, blood, pharmacokinetics)
  • Humans
  • Middle Aged
  • Multiple Myeloma (blood, drug therapy, metabolism, pathology)
  • Piperidines (administration & dosage, adverse effects, blood, pharmacokinetics)
  • Recurrence

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