Literature DB >> 22271900

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

Deborah M Stephens1, Amy S Ruppert, Kristie Blum, Jeffrey Jones, Joseph M Flynn, Amy J Johnson, Jia Ji, Mitch A Phelps, Michael R Grever, John C Byrd.   

Abstract

Older chronic lymphocytic leukemia patients have poor outcomes with standard treatments and are underrepresented in clinical trials. We retrospectively reviewed outcomes of refractory chronic lymphocytic leukemia patients in two age categories (≥70 and <70 years) treated with single-agent flavopiridol, a drug active in genomically high-risk patients, during two trials. No significant difference between older and younger patients was observed in response rates (43 vs. 47%) or progression-free survival (median 8.7 vs. 9.9 months, P>0.80). Although overall survival was worse in older patients (median 2.1 vs. 2.4 years, P=0.02); when adjusted for other factors this difference was no longer significant (P≥0.10). With the exception of infections (older 29% vs. younger 62%) no significant association with toxicity was observed. These data demonstrate that flavopiridol administration to older chronic lymphocytic leukemia patients is feasible, tolerable, and may have similar efficacy to that in younger patients. Development of treatment approaches including flavopiridol should be considered for these older patients.

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Year:  2012        PMID: 22271900      PMCID: PMC3291598          DOI: 10.3324/haematol.2011.047324

Source DB:  PubMed          Journal:  Haematologica        ISSN: 0390-6078            Impact factor:   9.941


  21 in total

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Authors:  M Hallek; K Fischer; G Fingerle-Rowson; A M Fink; R Busch; J Mayer; M Hensel; G Hopfinger; G Hess; U von Grünhagen; M Bergmann; J Catalano; P L Zinzani; F Caligaris-Cappio; J F Seymour; A Berrebi; U Jäger; B Cazin; M Trneny; A Westermann; C M Wendtner; B F Eichhorst; P Staib; A Bühler; D Winkler; T Zenz; S Böttcher; M Ritgen; M Mendila; M Kneba; H Döhner; S Stilgenbauer
Journal:  Lancet       Date:  2010-10-02       Impact factor: 79.321

2.  National Cancer Institute-sponsored Working Group guidelines for chronic lymphocytic leukemia: revised guidelines for diagnosis and treatment.

Authors:  B D Cheson; J M Bennett; M Grever; N Kay; M J Keating; S O'Brien; K R Rai
Journal:  Blood       Date:  1996-06-15       Impact factor: 22.113

3.  Hematopoietic cell transplantation (HCT)-specific comorbidity index: a new tool for risk assessment before allogeneic HCT.

Authors:  Mohamed L Sorror; Michael B Maris; Rainer Storb; Frederic Baron; Brenda M Sandmaier; David G Maloney; Barry Storer
Journal:  Blood       Date:  2005-06-30       Impact factor: 22.113

4.  Underrepresentation of patients 65 years of age or older in cancer-treatment trials.

Authors:  L F Hutchins; J M Unger; J J Crowley; C A Coltman; K S Albain
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5.  Phase I to II multicenter study of oblimersen sodium, a Bcl-2 antisense oligonucleotide, in patients with advanced chronic lymphocytic leukemia.

Authors:  Susan M O'Brien; Charles C Cunningham; Anatoliy K Golenkov; Anna G Turkina; Steven C Novick; Kanti R Rai
Journal:  J Clin Oncol       Date:  2005-09-26       Impact factor: 44.544

6.  Chemoimmunotherapy with fludarabine, cyclophosphamide, and rituximab for relapsed and refractory chronic lymphocytic leukemia.

Authors:  William Wierda; Susan O'Brien; Sijin Wen; Stefan Faderl; Guillermo Garcia-Manero; Deborah Thomas; Kim-Anh Do; Jorge Cortes; Charles Koller; Miloslav Beran; Alessandra Ferrajoli; Francis Giles; Susan Lerner; Maher Albitar; Hagop Kantarjian; Michael Keating
Journal:  J Clin Oncol       Date:  2005-03-14       Impact factor: 44.544

7.  Early results of a chemoimmunotherapy regimen of fludarabine, cyclophosphamide, and rituximab as initial therapy for chronic lymphocytic leukemia.

Authors:  Michael J Keating; Susan O'Brien; Maher Albitar; Susan Lerner; William Plunkett; Francis Giles; Michael Andreeff; Jorge Cortes; Stefan Faderl; Deborah Thomas; Charles Koller; William Wierda; Michelle A Detry; Alice Lynn; Hagop Kantarjian
Journal:  J Clin Oncol       Date:  2005-03-14       Impact factor: 44.544

8.  Genomic aberrations and survival in chronic lymphocytic leukemia.

Authors:  H Döhner; S Stilgenbauer; A Benner; E Leupolt; A Kröber; L Bullinger; K Döhner; M Bentz; P Lichter
Journal:  N Engl J Med       Date:  2000-12-28       Impact factor: 91.245

9.  A population-based study of severity of comorbidity among patients with non-Hodgkin's lymphoma: prognostic impact independent of International Prognostic Index.

Authors:  Maryska L G Janssen-Heijnen; Dick Johan van Spronsen; Valery E P P Lemmens; Saskia Houterman; Kees D G W Verheij; Jan Willem W Coebergh
Journal:  Br J Haematol       Date:  2005-06       Impact factor: 6.998

10.  Structural basis for inhibition of cyclin-dependent kinase 9 by flavopiridol.

Authors:  Walter Filgueira de Azevedo; Fernanda Canduri; Nelson José Freitas da Silveira
Journal:  Biochem Biophys Res Commun       Date:  2002-04-26       Impact factor: 3.575

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  9 in total

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

Authors:  Jeffrey A Jones; Amy S Rupert; Ming Poi; Mitch A Phelps; Leslie Andritsos; Robert Baiocchi; Don M Benson; Kristie A Blum; Beth Christian; Joseph Flynn; Sam Penza; Pierluigi Porcu; Michael R Grever; John C Byrd
Journal:  Am J Hematol       Date:  2013-09-30       Impact factor: 10.047

2.  Inhibition of CDK9 by voruciclib synergistically enhances cell death induced by the Bcl-2 selective inhibitor venetoclax in preclinical models of acute myeloid leukemia.

Authors:  Daniel A Luedtke; Yongwei Su; Jun Ma; Xinyu Li; Steven A Buck; Holly Edwards; Lisa Polin; Juiwanna Kushner; Sijana H Dzinic; Kathryn White; Hai Lin; Jeffrey W Taub; Yubin Ge
Journal:  Signal Transduct Target Ther       Date:  2020-02-26

Review 3.  Emerging drug profile: cyclin-dependent kinase inhibitors.

Authors:  James S Blachly; John C Byrd
Journal:  Leuk Lymphoma       Date:  2013-07-29

4.  Cyclophosphamide, alvocidib (flavopiridol), and rituximab, a novel feasible chemoimmunotherapy regimen for patients with high-risk chronic lymphocytic leukemia.

Authors:  Deborah M Stephens; Amy S Ruppert; Kami Maddocks; Leslie Andritsos; Robert Baiocchi; Jeffrey Jones; Amy J Johnson; Lisa L Smith; Yuan Zhao; Yonghua Ling; Junan Li; Mitch A Phelps; Michael R Grever; John C Byrd; Joseph M Flynn
Journal:  Leuk Res       Date:  2013-07-15       Impact factor: 3.156

5.  A phase 1 clinical trial of flavopiridol consolidation in chronic lymphocytic leukemia patients following chemoimmunotherapy.

Authors:  Farrukh T Awan; Jeffrey A Jones; Kami Maddocks; Ming Poi; Michael R Grever; Amy Johnson; John C Byrd; Leslie A Andritsos
Journal:  Ann Hematol       Date:  2016-04-27       Impact factor: 3.673

Review 6.  Highlights of the Latest Advances in Research on CDK Inhibitors.

Authors:  Jonas Cicenas; Karthik Kalyan; Aleksandras Sorokinas; Asta Jatulyte; Deividas Valiunas; Algirdas Kaupinis; Mindaugas Valius
Journal:  Cancers (Basel)       Date:  2014-10-27       Impact factor: 6.639

Review 7.  Therapeutic advancement of chronic lymphocytic leukemia.

Authors:  Kang Lu; Xin Wang
Journal:  J Hematol Oncol       Date:  2012-09-16       Impact factor: 17.388

8.  Mitochondrial priming of chronic lymphocytic leukemia patients associates Bcl-xL dependence with alvocidib response.

Authors:  W E Pierceall; S L Warner; R J Lena; C Doykan; N Blake; M Elashoff; D V Hoff; D J Bearss; M H Cardone; L Andritsos; J C Byrd; M C Lanasa; M R Grever; A J Johnson
Journal:  Leukemia       Date:  2014-07-03       Impact factor: 11.528

9.  Inhibition of CDK9 by voruciclib synergistically enhances cell death induced by the Bcl-2 selective inhibitor venetoclax in preclinical models of acute myeloid leukemia.

Authors:  Daniel A Luedtke; Yongwei Su; Jun Ma; Xinyu Li; Steven A Buck; Holly Edwards; Lisa Polin; Juiwanna Kushner; Sijana H Dzinic; Kathryn White; Hai Lin; Jeffrey W Taub; Yubin Ge
Journal:  Signal Transduct Target Ther       Date:  2020-02-26
  9 in total

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