Literature DB >> 22534616

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.

Elias Jabbour1, 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.   

Abstract

UNLABELLED: We evaluated the efficacy and safety of the combination of twice-daily fludarabine and cytarabine (BIDFA) in patients with refractory/relapsed acute myeloid leukemia (AML), high-risk myelodysplastic syndromes (MDS), and chronic myeloid leukemia in myeloid blast phase (CML-BP). One hundred seven patients were enrolled. Overall, 27 (26%) patients responded with a complete remission (CR) rate of 21% and CR without platelet recovery (CRp) of 5%. The overall 4-week mortality rate was 9%. In conclusion, BIDFA is active and safe in heavily pretreated patients with myeloid malignancies.
BACKGROUND: The purpose of this study was to evaluate the efficacy and safety of the combination of twice-daily fludarabine and cytarabine (BIDFA) in patients with refractory/relapsed acute myeloid leukemia (AML), high-risk myelodysplastic syndromes (MDS), and chronic myeloid leukemia in myeloid blast phase (CML-BP). PATIENTS AND METHODS: One hundred seven patients with refractory/relapsed AML, intermediate and high-risk MDS, and CML-BP, with a performance status of 3 or less and normal organ function were treated. Patients received fludarabine 15 mg/m(2) intravenously (IV) every 12 hours on days 1 to 5 and cytarabine 0.5 g/m(2) IV over 2 hours every 12 hours on days 1 to 5. Gemtuzumab ozogamicin (GO) was administered at 3 mg/m(2) IV on day 1 in the first 59 patients. Patients with CML-BP were allowed to receive concomitant tyrosine kinase inhibitors.
RESULTS: Overall, 27 (26%) patients responded with a complete remission (CR) rate of 21% and CR without platelet recovery of 5%. The overall 4-week mortality rate was 9%. The CR rates for patients with relapsed AML with first CR duration greater than or equal to 12 months, relapsed AML with first CR duration less than 12 months, and refractory/relapsed AML beyond first salvage were 56%, 26%, and 11%, respectively. With a median follow-up of 7 months, the 6-month event-free survival, overall survival, and complete remission CR duration rates were 18%, 35%, and 70%, respectively.
CONCLUSION: BIDFA is active with an overall response rate of 26% in a heavily pretreated population. This combination is safe with a low 4-week mortality rate of 9%.
Copyright © 2012 Elsevier Inc. All rights reserved.

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Year:  2012        PMID: 22534616      PMCID: PMC3859239          DOI: 10.1016/j.clml.2012.03.003

Source DB:  PubMed          Journal:  Clin Lymphoma Myeloma Leuk        ISSN: 2152-2669


  19 in total

1.  Final report of the efficacy and safety of gemtuzumab ozogamicin (Mylotarg) in patients with CD33-positive acute myeloid leukemia in first recurrence.

Authors:  Richard A Larson; Eric L Sievers; Edward A Stadtmauer; Bob Löwenberg; Elihu H Estey; Hervé Dombret; Matthias Theobald; Dimitris Voliotis; John M Bennett; Maria Richie; Lance H Leopold; Mark S Berger; Matthew L Sherman; Michael R Loken; Jacques J M van Dongen; Irwin D Bernstein; Frederick R Appelbaum
Journal:  Cancer       Date:  2005-10-01       Impact factor: 6.860

2.  Outcome of patients with acute myelogenous leukemia after second salvage therapy.

Authors:  Francis Giles; Susan O'Brien; Jorge Cortes; Srdan Verstovsek; Carlos Bueso-Ramos; Jianqin Shan; Sherry Pierce; Guillermo Garcia-Manero; Michael Keating; Hagop Kantarjian
Journal:  Cancer       Date:  2005-08-01       Impact factor: 6.860

3.  Gemtuzumab ozogamicin, fludarabine, cytarabine and cyclosporine combination regimen in patients with CD33+ primary resistant or relapsed acute myeloid leukemia.

Authors:  Apostolia Tsimberidou; Jorge Cortes; Deborah Thomas; Guillermo Garcia-Manero; Srdan Verstovsek; Stephan Faderl; Maher Albitar; Hagop Kantarjian; Elihu Estey; Francis J Giles
Journal:  Leuk Res       Date:  2003-10       Impact factor: 3.156

4.  Fludarabine and arabinosylcytosine therapy of refractory and relapsed acute myelogenous leukemia.

Authors:  E Estey; W Plunkett; V Gandhi; M B Rios; H Kantarjian; M J Keating
Journal:  Leuk Lymphoma       Date:  1993-03

5.  Fludarabine potentiates metabolism of cytarabine in patients with acute myelogenous leukemia during therapy.

Authors:  V Gandhi; E Estey; M J Keating; W Plunkett
Journal:  J Clin Oncol       Date:  1993-01       Impact factor: 44.544

6.  Treatment of core-binding-factor in acute myelogenous leukemia with fludarabine, cytarabine, and granulocyte colony-stimulating factor results in improved event-free survival.

Authors:  Gautam Borthakur; Hagop Kantarjian; Xuemei Wang; William K Plunkett; Varsha V Gandhi; Stefan Faderl; Guillermo Garcia-Manero; Farhad Ravandi; Sherry Pierce; Elihu H Estey
Journal:  Cancer       Date:  2008-12-01       Impact factor: 6.860

7.  Cellular ara-CTP pharmacokinetics, response, and karyotype in newly diagnosed acute myelogenous leukemia.

Authors:  E H Estey; M J Keating; K B McCredie; E J Freireich; W Plunkett
Journal:  Leukemia       Date:  1990-02       Impact factor: 11.528

8.  Minimum dose of fludarabine for the maximal modulation of 1-beta-D-arabinofuranosylcytosine triphosphate in human leukemia blasts during therapy.

Authors:  V Gandhi; E Estey; M Du; M J Keating; W Plunkett
Journal:  Clin Cancer Res       Date:  1997-09       Impact factor: 12.531

9.  Modulation of the cellular metabolism of cytarabine and fludarabine by granulocyte-colony-stimulating factor during therapy of acute myelogenous leukemia.

Authors:  V Gandhi; E Estey; M Du; B Nowak; M J Keating; W Plunkett
Journal:  Clin Cancer Res       Date:  1995-02       Impact factor: 12.531

10.  Phase 2 clinical and pharmacologic study of clofarabine in patients with refractory or relapsed acute leukemia.

Authors:  Hagop Kantarjian; Varsha Gandhi; Jorge Cortes; Srdan Verstovsek; Min Du; Guillermo Garcia-Manero; Francis Giles; Stefan Faderl; Susan O'Brien; Sima Jeha; Jan Davis; Zeev Shaked; Adam Craig; Michael Keating; William Plunkett; Emil J Freireich
Journal:  Blood       Date:  2003-06-05       Impact factor: 22.113

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  8 in total

1.  A phase I/II randomized trial of clofarabine or fludarabine added to idarubicin and cytarabine for adults with relapsed or refractory acute myeloid leukemia.

Authors:  Nicholas J Short; Hagop Kantarjian; Farhad Ravandi; Xuelin Huang; Lianchun Xiao; Guillermo Garcia-Manero; William Plunkett; Varsha Gandhi; Koji Sasaki; Naveen Pemmaraju; Naval G Daver; Gautam Borthakur; Nitin Jain; Marina Konopleva; Zeev Estrov; Tapan M Kadia; William G Wierda; Courtney D DiNardo; Mark Brandt; Susan M O'Brien; Jorge E Cortes; Elias Jabbour
Journal:  Leuk Lymphoma       Date:  2017-07-18

2.  A phase I study of fludarabine, cytarabine, and oxaliplatin therapy in patients with relapsed or refractory acute myeloid leukemia.

Authors:  Apostolia Maria Tsimberidou; Michael J Keating; Elias J Jabbour; Farhad Ravandi-Kashani; Susan O'Brien; Elihu Estey; Neby Bekele; William K Plunkett; Hagop Kantarjian; Gautam Borthakur
Journal:  Clin Lymphoma Myeloma Leuk       Date:  2014-02-03

3.  Treated secondary acute myeloid leukemia: a distinct high-risk subset of AML with adverse prognosis.

Authors:  Prajwal Boddu; Hagop M Kantarjian; Guillermo Garcia-Manero; Farhad Ravandi; Srdan Verstovsek; Elias Jabbour; Gautam Borthakur; Marina Konopleva; Kapil N Bhalla; Naval Daver; Courtney D DiNardo; Christopher B Benton; Koichi Takahashi; Zeev Estrov; Sherry R Pierce; Michael Andreeff; Jorge E Cortes; Tapan M Kadia
Journal:  Blood Adv       Date:  2017-07-19

Review 4.  Management of Relapsed/Refractory Acute Myeloid Leukemia in the Elderly: Current Strategies and Developments.

Authors:  Jeffrey C Bryan; Elias J Jabbour
Journal:  Drugs Aging       Date:  2015-08       Impact factor: 3.923

5.  Initial Report of a Phase I Study of LY2510924, Idarubicin, and Cytarabine in Relapsed/Refractory Acute Myeloid Leukemia.

Authors:  Prajwal Boddu; Gautam Borthakur; Mythili Koneru; Xuelin Huang; Kiran Naqvi; William Wierda; Prithviraj Bose; Elias Jabbour; Zeev Estrov; Jan Burger; Yesid Alvarado; April Deshmukh; Ami Patel; Antonio Cavazos; Lina Han; Jorge E Cortes; Hagop Kantarjian; Michael Andreeff; Marina Konopleva
Journal:  Front Oncol       Date:  2018-09-24       Impact factor: 6.244

Review 6.  Management of Chronic Myeloid Leukemia in Advanced Phase.

Authors:  Massimiliano Bonifacio; Fabio Stagno; Luigi Scaffidi; Mauro Krampera; Francesco Di Raimondo
Journal:  Front Oncol       Date:  2019-10-25       Impact factor: 6.244

Review 7.  Acute myeloid leukemia: current progress and future directions.

Authors:  Hagop Kantarjian; Tapan Kadia; Courtney DiNardo; Naval Daver; Gautam Borthakur; Elias Jabbour; Guillermo Garcia-Manero; Marina Konopleva; Farhad Ravandi
Journal:  Blood Cancer J       Date:  2021-02-22       Impact factor: 11.037

8.  Flotetuzumab as salvage immunotherapy for refractory acute myeloid leukemia.

Authors:  Geoffrey L Uy; Ibrahim Aldoss; Matthew C Foster; Peter H Sayre; Matthew J Wieduwilt; Anjali S Advani; John E Godwin; Martha L Arellano; Kendra L Sweet; Ashkan Emadi; Farhad Ravandi; Harry P Erba; Michael Byrne; Laura Michaelis; Max S Topp; Norbert Vey; Fabio Ciceri; Matteo Giovanni Carrabba; Stefania Paolini; Gerwin A Huls; Mojca Jongen-Lavrencic; Martin Wermke; Patrice Chevallier; Emmanuel Gyan; Christian Récher; Patrick J Stiff; Kristen M Pettit; Bob Löwenberg; Sarah E Church; Erica Anderson; Jayakumar Vadakekolathu; Marianne Santaguida; Michael P Rettig; John Muth; Teia Curtis; Erin Fehr; Kuo Guo; Jian Zhao; Ouiam Bakkacha; Kenneth Jacobs; Kathy Tran; Patrick Kaminker; Maya Kostova; Ezio Bonvini; Roland B Walter; Jan K Davidson-Moncada; Sergio Rutella; John F DiPersio
Journal:  Blood       Date:  2021-02-11       Impact factor: 25.476

  8 in total

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