A phase I trial of flavopiridol in relapsed multiple myeloma.
OBJECTIVE
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).
Division of Hematology, The Ohio State University, B321 Starling Loving Hall, 320 West 10th Avenue, Columbus, OH, 43210, USA, Craig.Hofmeister@osumc.edu.
Craig C
CC
Hofmeister
Ming
M
Poi
Mindy A
MA
Bowers
Weiqiang
W
Zhao
Mitch A
MA
Phelps
Don M
DM
Benson
Eric H
EH
Kraut
Sherif
S
Farag
Yvonne A
YA
Efebera
Jennifer
J
Sexton
Thomas S
TS
Lin
Michael
M
Grever
John C
JC
Byrd
D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics; D004305:Dose-Response Relationship, Drug; D005419:Flavonoids / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics; D006801:Humans; D008875:Middle Aged; D009101:Multiple Myeloma / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D010880:Piperidines / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics; D012008:Recurrence
D000970:Antineoplastic Agents; D005419:Flavonoids; D010880:Piperidines; C077990:alvocidib