Flavopiridol treatment of patients aged 70 or older with refractory or relapsed chronic lymphocytic leukemia is a feasible and active therapeutic approach

Haematologica

Volumn 97, Issue 3, 2012, Pages 423-427

  Stephens, Deborah M ^a   Ruppert, Amy S ^a   Blum, Kristie ^a   Jones, Jeffrey ^a   Flynn, Joseph M ^a   Johnson, Amy J ^a   Ji, Jia ^b   Phelps, Mitch A ^b   Grever, Michael R ^a   Byrd, John C ^a,b  

^a OHIO STATE UNIVERSITY   (United States)

^b OHIO STATE UNIVERSITY   (United States)

Author keywords

Chronic lymphocytic leukemia; Elderly; Flavopiridol; Refractory; Relapsed

Indexed keywords

FLAVOPIRIDOL;

ADULT; AGED; ANEMIA; ARTICLE; BILIRUBIN BLOOD LEVEL; CANCER RELAPSE; CANCER STAGING; CHRONIC LYMPHATIC LEUKEMIA; CONTINUOUS INFUSION; CONTROLLED STUDY; CREATININE BLOOD LEVEL; CYTOGENETICS; CYTOKINE RELEASE SYNDROME; DIARRHEA; DRUG DOSE ESCALATION; DRUG EFFICACY; DRUG SAFETY; DRUG TOLERABILITY; FATIGUE; FEMALE; GERIATRIC CARE; HUMAN; KARYOTYPE; MAJOR CLINICAL STUDY; MALE; NEUTROPENIA; OVERALL SURVIVAL; PROGRESSION FREE SURVIVAL; REFRACTORY PERIOD; RETROSPECTIVE STUDY; THROMBOCYTOPENIA; TREATMENT RESPONSE; TUMOR LYSIS SYNDROME;

ADULT; AGE FACTORS; AGED; AGED, 80 AND OVER; ANTINEOPLASTIC AGENTS; FLAVONOIDS; HUMANS; LEUKEMIA, LYMPHOCYTIC, CHRONIC, B-CELL; MIDDLE AGED; PIPERIDINES; RECURRENCE; SURVIVAL ANALYSIS; TREATMENT OUTCOME;

EID: 84863393289     PISSN: 03906078     EISSN: 15928721     Source Type: Journal    
DOI: 10.3324/haematol.2011.047324     Document Type: Article

References (24)

1. Hutchins LF, Unger JM, Crowley JJ, Coltman CA Jr, Albain KS. Under-representation of patients 65 years of age or older in cancer-treatment trials. N Engl J Med. 1999;341(27):2061-7.
2. Ries LA, Melbert D, Krapcho M, Stinchcomb DF, Howlader N, Horner MJ. SEER Clinical Statistics Review, 1975-2005. Report. Bethesda, MD; 2008.
3. Eichhorst B, Goede V, Hallek M. Treatment of elderly patients with chronic lymphocytic leukemia. Leuk Lymphoma. 2009;50(2): 171-8.
4. Rai KR, Peterson BL, Appelbaum FR, Kolitz J, Elias L, Shepherd L, et al. Fludarabine compared with chlorambucil as primary therapy for chronic lymphocytic leukemia. N Engl J Med. 2000;343(24):1750-7.
5. Eichhorst BF, Busch R, Stilgenbauer S, Stauch M, Bergmann MA, Ritgen M, et al. First-line therapy with fludarabine compared with chlorambucil does not result in a major benefit for elderly patients with advanced chronic lymphocytic leukemia. Blood. 2009;114(16):3382-91.
6. Keating MJ, O'Brien S, Albitar M, Lerner S, Plunkett W, Giles F, et al. Early results of a chemoimmunotherapy regimen of fludarabine, cyclophosphamide, and rituximab as initial therapy for chronic lymphocytic leukemia. J Clin Oncol. 2005;23(18):4079-88.
7. Hallek M, Fischer K, Fingerle-Rowson G, Fink AM, Busch R, Mayer J, et al. Addition of rituximab to fludarabine and cyclophosphamide in patients with chronic lymphocytic leukaemia: a randomised, open-label, phase 3 trial. Lancet. 2010;376(9747):1164-74.
8. Wierda W, O'Brien S, Wen S, Faderl S, Garcia-Manero G, Thomas D, et al. Chemoimmunotherapy with fludarabine, cyclophosphamide, and rituximab for relapsed and refractory chronic lymphocytic leukemia. J Clin Oncol. 2005;23(18): 4070-8.
9. de Azevedo WF Jr, Canduri F, da Silveira NJ. Structural basis for inhibition of cyclindependent kinase 9 by flavopiridol. Bioche Biophys Res Commun. 2002;293(1):566-71.
10. Lin TS, Ruppert AS, Johnson AJ, Fischer B, Heerema NA, Andritsos LA, 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(35):6012-8.
11. Byrd JC, Lin TS, Dalton JT, Wu D, Phelps MA, Fischer B, 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(2):399-404.
12. Phelps MA, Lin TS, Johnson AJ, Hurh E, Rozewski DM, Farley KL, 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(12):2637-45.
13. Cheson BD, Bennett JM, Grever M, Kay N, Keating MJ, O'Brien S, et al. National Cancer Institute-sponsored Working Group guidelines for chronic lymphocytic leukemia: revised guidelines for diagnosis and treatment. Blood. 1996;87(12):4990-7.
14. Blum W, Phelps MA, Klisovic RB, Rozewski DM, Ni W, Albanese KA, et al. Phase I clinical and pharmacokinetic study of a novel schedule of flavopiridol in relapsed or refractory acute leukemias. Haematologica. 2010;95(7):1098-105.
15. Chanan-Khan A, Miller KC, Musial L, Lawrence D, Padmanabhan S, Takeshita K, et al. Clinical efficacy of lenalidomide in patients with relapsed or refractory chronic lymphocytic leukemia: results of a phase II study. J Clin Oncol. 2006;24(34):5343-9.
16. Ferrajoli A, Lee BN, Schlette EJ, O'Brien SM, Gao H, Wen S, et al. Lenalidomide induces complete and partial remissions in patients with relapsed and refractory chronic lymphocytic leukemia. Blood. 2008;111(11):5291-7.
17. Wierda WG, Kipps TJ, Mayer J, Stilgenbauer S, Williams CD, Hellmann A, et al. Ofatumumab as single-agent CD20 immunotherapy in fludarabine-refractory chronic lymphocytic leukemia. J Clin Oncol. 2010;28(10):1749-55.
18. Lanasa MC, Andritsos L, Brown JR, Gabrilove J, Caligaris-Cappio F, Larson R, et al. Interim analysis of EFC6663, a multicenter phase 2 study of alvocidib (flavopiridol), demonstrates clinical responses among patients with fludarabine refractory CLL. Blood (ASH Annual Meeting Abstracts).116: Abstract 58.
19. O'Brien SM, Cunningham CC, Golenkov AK, Turkina AG, Novick SC, Rai KR. Phase I to II multicenter study of oblimersen sodium, a Bcl-2 antisense oligonucleotide, in patients with advanced chronic lymphocytic leukemia. J Clin Oncol. 2005;23(30): 7697-702.
20. O'Brien SM, Claxton DF, Crump M, Faderl S, Kipps T, Keating MJ, et al. Phase I study of obatoclax mesylate (GX15-070), a small molecule pan-Bcl-2 family antagonist, in patients with advanced chronic lymphocytic leukemia. Blood. 2009;113(2):299-305.
21. Wilson WH, O'Connor OA, Roberts AW. ABT-263 activity and safety in patients with relapsed or refractory lymphoid malignancies in particular chronic lymphocytic leukemia/small lymphocytic lymphoma. J Clin Oncol. 2009;27(Suppl): Abstract 8574.
22. Janssen-Heijnen ML, van Spronsen DJ, Lemmens VE, Houterman S, Verheij KD, Coebergh JW. A population-based study of severity of comorbidity among patients with non-Hodgkin's lymphoma: prognostic impact independent of International Prognostic Index. Br J Haematol. 2005; 129(5):597-606.
23. Sorror ML, Maris MB, Storb R, Baron F, Sandmaier BM, Maloney DG, et al. Hematopoietic cell transplantation (HCT)-specific comorbidity index: a new tool for risk assessment before allogeneic HCT. Blood. 2005;106(8):2912-9.
24. Dohner H, Stilgenbauer S, Benner A, Leupolt E, Krober A, Bullinger L, et al. Genomic aberrations and survival in chronic lymphocytic leukemia. N Engl J Med. 2000;343(26):1910-6.