Flavopiridol can be safely administered using a pharmacologically derived schedule and demonstrates activity in relapsed and refractory non-Hodgkin's lymphoma

American Journal of Hematology

Volumn 89, Issue 1, 2014, Pages 19-24

  Jones, Jeffrey A ^a   Rupert, Amy S ^a   Poi, Ming ^a   Phelps, Mitch A ^a   Andritsos, Leslie ^a   Baiocchi, Robert ^a   Benson, Don M ^a   Blum, Kristie A ^a   Christian, Beth ^a   Flynn, Joseph ^a   Penza, Sam ^a   Porcu, Pierluigi ^a   Grever, Michael R ^a   Byrd, John C ^a  

^a OHIO STATE UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

FLAVOPIRIDOL;

ADULT; AGED; ANEMIA; ANOREXIA; ANTINEOPLASTIC ACTIVITY; AREA UNDER THE CURVE; ARTICLE; AUTOLOGOUS STEM CELL TRANSPLANTATION; B CELL LYMPHOMA; BACTEREMIA; CANCER GROWTH; CANCER PATIENT; CANCER RECURRENCE; CLINICAL ARTICLE; COLITIS; CONTINUOUS INFUSION; DIARRHEA; DRUG ADMINISTRATION; DRUG DOSE ESCALATION; DRUG MEGADOSE; DRUG SAFETY; DRUG WITHDRAWAL; EPSTEIN BARR VIRUS; FATIGUE; FEBRILE NEUTROPENIA; FEMALE; HEMODIALYSIS; HUMAN; HYPERBILIRUBINEMIA; INFECTION; LARGE CELL LYMPHOMA; LEUKOPENIA; LYMPHOCYTOPENIA; MALE; MANTLE CELL LYMPHOMA; MAXIMUM PLASMA CONCENTRATION; MAXIMUM TOLERATED DOSE; MIDDLE AGED; MULTIMODALITY CANCER THERAPY; MULTIPLE CYCLE TREATMENT; NAUSEA; NEUTROPENIA; NK T CELL LYMPHOMA; OPPORTUNISTIC INFECTION; OTITIS MEDIA; PHASE 1 CLINICAL TRIAL; PNEUMONIA; PRIMARY CENTRAL NERVOUS SYSTEM LYMPHOMA; PRIORITY JOURNAL; RADIOIMMUNOTHERAPY; THROMBOCYTOPENIA; TREATMENT RESPONSE; TUMOR CELL DESTRUCTION; VERY ELDERLY; VOMITING;

ADULT; AGED; AGED, 80 AND OVER; ANTINEOPLASTIC AGENTS; DRUG ADMINISTRATION SCHEDULE; FEMALE; FLAVONOIDS; HUMANS; LYMPHOMA, NON-HODGKIN; MALE; MAXIMUM TOLERATED DOSE; MIDDLE AGED; PIPERIDINES; PROTEIN KINASE INHIBITORS; RECURRENCE; TREATMENT OUTCOME;

EID: 84892853268     PISSN: 03618609     EISSN: 10968652     Source Type: Journal    
DOI: 10.1002/ajh.23568     Document Type: Article

References (19)

1. Rapoport AP, Simons-Evelyn M, Chen T, et al. Flavopiridol induces apoptosis and caspase-3 activation of a newly characterized Burkitt's lymphoma cell line containing mutant p53 genes. Blood Cells Mol Dis 2001;27:610-624.
2. Venkataraman G, Maududi T, Ozpuyan F, et al. Induction of apoptosis and down regulation of cell cycle proteins in mantle cell lymphoma by flavopiridol treatment. Leuk Res 2006;30:1377-1384.
3. Myatt D, Johnson L, Baumli S, Siligardi G. The binding of flavopiridol to blood serum albumin. Chirality 2010;22 Suppl 1:E40-43.
4. Arguello F, Alexander M, Sterry JA, et al. Flavopiridol induces apoptosis of normal lymphoid cells, causes immunosuppression, and has potent antitumor activity in vivo against human leukemia and lymphoma xenografts. Blood 1998;91:2482-2490.
5. Kouroukis CT, Belch A, Crump M, et al. Flavopiridol in untreated or relapsed mantle-cell lymphoma: Results of a phase II study of the National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol 2003;21:1740-1745.
6. Lin TS, Howard OM, Neuberg DS, et al. Seventy-two hour continuous infusion flavopiridol in relapsed and refractory mantle cell lymphoma. Leuk Lymphoma 2002;43:793-797.
7. Byrd JC, Shinn C, Waselenko JK, et al. Flavopiridol induces apoptosis in chronic lymphocytic leukemia cells via activation of caspase-3 without evidence of bcl-2 modulation or dependence on functional p53. Blood 1998;92:3804-3816.
8. Phelps MA, Lin TS, Johnson AJ, et al. Clinical response and pharmacokinetics from a phase 1 study of an active dosing schedule of flavopiridol in relapsed chronic lymphocytic leukemia. Blood 2009;113:2637-2645.
9. Byrd JC, Lin TS, Dalton JT, et al. Flavopiridol administered using a pharmacologically derived schedule is associated with marked clinical efficacy in refractory, genetically high-risk chronic lymphocytic leukemia. Blood 2007;109:399-404.
10. Lin TS, Ruppert AS, Johnson AJ, et al. Phase II study of flavopiridol in relapsed chronic lymphocytic leukemia demonstrating high response rates in genetically high-risk disease. J Clin Oncol 2009;27:6012-6018.
11. Cheson BD, Horning SJ, Coiffier B, et al. Report of an international workshop to standardize response criteria for non-Hodgkin's lymphomas. NCI Sponsored International Working Group. J Clin Oncol 1999;17:1244.
12. Phelps MA, Rozewski DM, Johnston JS, et al. Development and validation of a sensitive liquid chromatography/mass spectrometry method for quantitation of flavopiridol in plasma enables accurate estimation of pharmacokinetic parameters with a clinically active dosing schedule. J Chromatogr B Analyt Technol Biomed Life Sci 2008;868:110-115.
13. Stephens DM, Ruppert AS, Blum K, et al. Flavopiridol treatment of patients aged 70 or older with refractory or relapsed chronic lymphocytic leukemia is a feasible and active therapeutic approach. Haematologica 2012;97:423-427.
14. Blum W, Phelps MA, Klisovic RB, et al. Phase I clinical and pharmacokinetic study of a novel schedule of flavopiridol in relapsed or refractory acute leukemias. Haematologica 2010;95:1098-1105.
15. Holkova B, Perkins EB, Ramakrishnan V, et al. Phase I trial of bortezomib (PS-341; NSC 681239) and alvocidib (flavopiridol; NSC 649890) in patients with recurrent or refractory B-cell neoplasms. Clin Cancer Res 2011;17:3388-3397.
16. Messmann RA, Ullmann CD, Lahusen T, et al. Flavopiridol-related proinflammatory syndrome is associated with induction of interleukin-6. Clin Cancer Res 2003;9:562-570.
17. Karp JE, Smith BD, Resar LS, et al. Phase 1 and pharmacokinetic study of bolus-infusion flavopiridol followed by cytosine arabinoside and mitoxantrone for acute leukemias. Blood 2011;117:3302-3310.
18. Lin TS, Blum KA, Fischer DB, et al. Flavopiridol, fludarabine, and rituximab in mantle cell lymphoma and indolent B-cell lymphoproliferative disorders. J Clin Oncol 2010;28:418-423.
19. Mahoney E, Lucas DM, Gupta SV, et al. ER stress and autophagy: New discoveries in the mechanism of action and drug resistance of the cyclin-dependent kinase inhibitor flavopiridol. Blood 2012;120:1262-1273.