Literature DB >> 22282348

Clofarabine plus low-dose cytarabine followed by clofarabine plus low-dose cytarabine alternating with decitabine in acute myeloid leukemia frontline therapy for older patients.

Stefan Faderl1, Farhad Ravandi, Xuelin Huang, Xuemei Wang, Elias Jabbour, Guillermo Garcia-Manero, Tapan Kadia, Alessandra Ferrajoli, Marina Konopleva, Gautam Borthakur, Jan Burger, Jennie Feliu, Hagop M Kantarjian.   

Abstract

BACKGROUND: Standard therapy for older patients with acute myeloid leukemia (AML) has a poor outcome. The authors have designed a combination of clofarabine plus low-dose cytarabine followed by a prolonged consolidation alternating with decitabine.
METHODS: Sixty patients with a median age of 70 years (range, 60-81 years) with newly diagnosed AML were included. They received clofarabine 20 mg/m(2) intravenously daily for 5 days plus cytarabine 20 mg subcutaneously twice daily for 10 days. Responding patients continued for up to 17 courses of consolidation therapy including decitabine.
RESULTS: Forty of 59 evaluable patients responded (66%). Complete remission rate was 58%. Median relapse-free survival (RFS) was 14.1 (95% confidence interval [CI], 6.9 to not estimable), and median overall survival (OS) was 12.7 months (95% CI, 8.8 to not estimable). Median OS of responding patients (complete response [CR]/CR with platelet count <100 × 109/L) was 24.2 months (95% CI, 17 to not estimable). Compared with a historical group of patients who received clofarabine plus low-dose cytarabine with a shorter consolidation, RFS was not statistically different. Induction mortality was low (7% at 8 weeks) and toxicities manageable.
CONCLUSIONS: Clofarabine plus low-dose cytarabine alternating with decitabine in consolidation is active in older patients with newly diagnosed AML. The benefits of a prolonged consolidation remain unproven.
Copyright © 2012 American Cancer Society.

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Year:  2012        PMID: 22282348      PMCID: PMC3907176          DOI: 10.1002/cncr.27429

Source DB:  PubMed          Journal:  Cancer        ISSN: 0008-543X            Impact factor:   6.860


  15 in total

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Journal:  Blood       Date:  2011-03-24       Impact factor: 22.113

2.  European development of clofarabine as treatment for older patients with acute myeloid leukemia considered unsuitable for intensive chemotherapy.

Authors:  Alan K Burnett; Nigel H Russell; Jonathan Kell; Michael Dennis; Donald Milligan; Stefania Paolini; John Yin; Dominic Culligan; Peter Johnston; John Murphy; Mary-Frances McMullin; Ann Hunter; Emma Das-Gupta; Richard Clark; Robert Carr; Robert K Hills
Journal:  J Clin Oncol       Date:  2010-04-12       Impact factor: 44.544

3.  Clinical response and miR-29b predictive significance in older AML patients treated with a 10-day schedule of decitabine.

Authors:  William Blum; Ramiro Garzon; Rebecca B Klisovic; Sebastian Schwind; Alison Walker; Susan Geyer; Shujun Liu; Violaine Havelange; Heiko Becker; Larry Schaaf; Jon Mickle; Hollie Devine; Cheryl Kefauver; Steven M Devine; Kenneth K Chan; Nyla A Heerema; Clara D Bloomfield; Michael R Grever; John C Byrd; Miguel Villalona-Calero; Carlo M Croce; Guido Marcucci
Journal:  Proc Natl Acad Sci U S A       Date:  2010-04-05       Impact factor: 11.205

4.  Phase II study of clofarabine monotherapy in previously untreated older adults with acute myeloid leukemia and unfavorable prognostic factors.

Authors:  Hagop M Kantarjian; Harry P Erba; David Claxton; Martha Arellano; Roger M Lyons; Tibor Kovascovics; Janice Gabrilove; Michael Craig; Dan Douer; Michael Maris; Stephen Petersdorf; Paul J Shami; Andrew M Yeager; Stephen Eckert; Rekha Abichandani; Stefan Faderl
Journal:  J Clin Oncol       Date:  2009-12-21       Impact factor: 44.544

5.  Multicenter, phase II study of decitabine for the first-line treatment of older patients with acute myeloid leukemia.

Authors:  Amanda F Cashen; Gary J Schiller; Margaret R O'Donnell; John F DiPersio
Journal:  J Clin Oncol       Date:  2009-12-21       Impact factor: 44.544

6.  Complete remission and early death after intensive chemotherapy in patients aged 60 years or older with acute myeloid leukaemia: a web-based application for prediction of outcomes.

Authors:  Utz Krug; Christoph Röllig; Anja Koschmieder; Achim Heinecke; Maria Cristina Sauerland; Markus Schaich; Christian Thiede; Michael Kramer; Jan Braess; Karsten Spiekermann; Torsten Haferlach; Claudia Haferlach; Steffen Koschmieder; Christian Rohde; Hubert Serve; Bernhard Wörmann; Wolfgang Hiddemann; Gerhard Ehninger; Wolfgang E Berdel; Thomas Büchner; Carsten Müller-Tidow
Journal:  Lancet       Date:  2010-12-03       Impact factor: 79.321

7.  Intensive chemotherapy does not benefit most older patients (age 70 years or older) with acute myeloid leukemia.

Authors:  Hagop Kantarjian; Farhad Ravandi; Susan O'Brien; Jorge Cortes; Stefan Faderl; Guillermo Garcia-Manero; Elias Jabbour; William Wierda; Tapan Kadia; Sherry Pierce; Jianqin Shan; Michael Keating; Emil J Freireich
Journal:  Blood       Date:  2010-07-28       Impact factor: 22.113

8.  A randomized study of clofarabine versus clofarabine plus low-dose cytarabine as front-line therapy for patients aged 60 years and older with acute myeloid leukemia and high-risk myelodysplastic syndrome.

Authors:  Stefan Faderl; Farhad Ravandi; Xuelin Huang; Guillermo Garcia-Manero; Alessandra Ferrajoli; Zeev Estrov; Gautam Borthakur; Srdan Verstovsek; Deborah A Thomas; Monica Kwari; Hagop M Kantarjian
Journal:  Blood       Date:  2008-06-18       Impact factor: 22.113

9.  Risk factors and decision criteria for intensive chemotherapy in older patients with acute myeloid leukemia.

Authors:  Jean-Valère Malfuson; Anne Etienne; Pascal Turlure; Thierry de Revel; Xavier Thomas; Nathalie Contentin; Christine Terré; Sophie Rigaudeau; Dominique Bordessoule; Norbert Vey; Claude Gardin; Hervé Dombret
Journal:  Haematologica       Date:  2008-10-06       Impact factor: 9.941

10.  Phase I clinical and pharmacology study of clofarabine in patients with solid and hematologic cancers.

Authors:  Hagop M Kantarjian; Varsha Gandhi; Peter Kozuch; Stefan Faderl; Francis Giles; Jorge Cortes; Susan O'Brien; Nuhad Ibrahim; Fadlo Khuri; Min Du; Mary Beth Rios; Sima Jeha; Peter McLaughlin; William Plunkett; Michael Keating
Journal:  J Clin Oncol       Date:  2003-03-15       Impact factor: 44.544

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  29 in total

1.  Outcomes of patients with myelodysplatic syndrome and chronic myelomonocytic leukemia post clofarabine failure.

Authors:  Hady Ghanem; Guillermo Garcia-Manero; Stefan Faderl; Farhad Ravandi; Jorge Cortes; Lakshmikanth Katragadda; Susan O'Brien; Naval Daver; Sherry Pierce; Tapan Kadia; Hagop Kantarjian; Elias Jabbour
Journal:  Ther Adv Hematol       Date:  2014-04

2.  Twice-daily fludarabine and cytarabine combination with or without gentuzumab ozogamicin is effective in patients with relapsed/refractory acute myeloid leukemia, high-risk myelodysplastic syndrome, and blast- phase chronic myeloid leukemia.

Authors:  Elias Jabbour; Guillermo Garcia-Manero; Jorge Cortes; Farhad Ravandi; William Plunkett; Varsha Gandhi; Stefan Faderl; Susan O'Brien; Gautam Borthakur; Tapan Kadia; Jan Burger; Marina Konopleva; Mark Brandt; Xuelin Huang; Hagop Kantarjian
Journal:  Clin Lymphoma Myeloma Leuk       Date:  2012-04-24

Review 3.  Epigenetic aspects of MDS and its molecular targeted therapy.

Authors:  Jumpei Yamazaki; Jean-Pierre J Issa
Journal:  Int J Hematol       Date:  2012-10-10       Impact factor: 2.490

4.  Clofarabine Plus Low-Dose Cytarabine Is as Effective as and Less Toxic Than Intensive Chemotherapy in Elderly AML Patients.

Authors:  Koichi Takahashi; Hagop Kantarjian; Guillermo Garcia-Manero; Gautam Borthakur; Tapan Kadia; Courtney DiNardo; Elias Jabbour; Sherry Pierce; Zeev Estrov; Marina Konopleva; Michael Andreeff; Farhad Ravandi; Jorge Cortes
Journal:  Clin Lymphoma Myeloma Leuk       Date:  2015-11-24

5.  Phase I study of oral clofarabine consolidation in adults aged 60 and older with acute myeloid leukemia.

Authors:  Meagan A Jacoby; Michael G Martin; Geoffrey L Uy; Peter Westervelt; John F Dipersio; Amanda Cashen; Keith Stockerl-Goldstein; Ravi Vij; Jingqin Luo; Teresa Reineck; Noel Bernabe; Camille N Abboud
Journal:  Am J Hematol       Date:  2014-03-03       Impact factor: 10.047

6.  Acute myeloid leukemia after myelodysplastic syndrome and failure of therapy with hypomethylating agents: an emerging entity with a poor prognosis.

Authors:  Elias Jabbour; Hady Ghanem; Xuelin Huang; Farhad Ravandi; Guillermo Garcia-Manero; Susan O'Brien; Stephan Faderl; Sherry Pierce; Sangbum Choi; Srdan Verstovsek; Mark Brandt; Jorge Cortes; Hagop Kantarjian
Journal:  Clin Lymphoma Myeloma Leuk       Date:  2013-11-15

7.  New treatments and strategies in acute myeloid leukemia.

Authors:  Farhad Ravandi
Journal:  Clin Lymphoma Myeloma Leuk       Date:  2011-04-30

Review 8.  Strategies to reduce relapse after allogeneic hematopoietic cell transplantation in acute myeloid leukemia.

Authors:  Raya Mawad; Jack M Lionberger; John M Pagel
Journal:  Curr Hematol Malig Rep       Date:  2013-06       Impact factor: 3.952

9.  Clofarabine and Cytarabine Regimen for Acute Myeloid Leukemia.

Authors:  Kristin V Ho; Dominic A Solimando; J Aubrey Waddell
Journal:  Hosp Pharm       Date:  2015-11-24

10.  Clofarabine in the treatment of acute myeloid leukemia in older adults.

Authors:  Stephen Tiley; David Claxton
Journal:  Ther Adv Hematol       Date:  2013-02
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