Difference between revisions of "Acute myeloid leukemia"
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=Induction therapy= | =Induction therapy= | ||
+ | ==Clofarabine, Idarubicin, and Cytarabine (CIA) Induction== | ||
+ | ===Regimen, Nazha et al.2013=== | ||
+ | Level of Evidence: | ||
+ | <span | ||
+ | style="background:#EEEE00; | ||
+ | padding:3px 6px 3px 6px; | ||
+ | border-color:black; | ||
+ | border-width:2px; | ||
+ | border-style:solid;">Phase II</span> | ||
+ | |||
+ | *[[Clofarabine(Clolar)]] 20 mg/m2 IV over 1 hour once per day on days 1-5 | ||
+ | *[[Idarubicin (Idamycin)]] 10 mg/m2 IV over 30 minutes once per day on days 1-3 | ||
+ | *[[Cytarabine(Cytosar)]] 1000 mg/m2 IV over 2 hours once per day on days 1-5 | ||
+ | |||
+ | '''5-day course'''; patients with only partial remission underwent a second course with the same drugs, doses, and schedule | ||
+ | |||
+ | Supportive medications: | ||
+ | *Prophylactic levofloxacin, itraconazole, and valacyclovir were administered to all patients | ||
+ | *[[Filgrastim (Neupogen)|Granulocyte colony-stimulating factor]] neither mandated nor forbidden and given per physician discretion | ||
+ | |||
+ | Patients who achieved a CR or CRi (complete remission with incomplete platelet recovery) proceeded to [[#Clofarabine.2C_Idarubicin.2C_and Cytarabine_.28CIA.29_Consolidation|Clofarabine, Idarubicin, and Cytarabine (CIA) Consolidation]] | ||
+ | |||
+ | ===References=== | ||
+ | # Nazha A, Kantarjian H, Ravandi F, Huang X, Choi S, Garcia-Manero G, Jabbour E, Borthakur G, Kadia T, Konopleva M, Cortes J, Ferrajoli A, Kornblau S, Daver N, Pemmaraju N, Andreeff M, Estrov Z, Du M, Brandt M, Faderl S. Clofarabine, idarubicin, and cytarabine (CIA) as frontline therapy for patients ≤60 years with newly diagnosed acute myeloid leukemia.Am J Hematol. 2013 Nov;88(11):961-6. doi: 10.1002/ajh.23544. Epub 2013 Sep 9. [http://onlinelibrary.wiley.com/doi/10.1002/ajh.23544/references long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/23877926 PubMed] | ||
+ | |||
==7+3 Cytarabine & Daunorubicin ("Standard" or "conventional" dose)== | ==7+3 Cytarabine & Daunorubicin ("Standard" or "conventional" dose)== | ||
===Regimen #1=== | ===Regimen #1=== | ||
Line 236: | Line 261: | ||
=Consolidation therapy= | =Consolidation therapy= | ||
+ | == Clofarabine, Idarubicin, and Cytarabine (CIA) Consolidation == | ||
+ | ===Regimen, Nazha et al.2013=== | ||
+ | Level of Evidence: | ||
+ | <span | ||
+ | style="background:#EEEE00; | ||
+ | padding:3px 6px 3px 6px; | ||
+ | border-color:black; | ||
+ | border-width:2px; | ||
+ | border-style:solid;">Phase II</span> | ||
+ | |||
+ | To be preceded by [[#Clofarabine.2C_Idarubicin.2C_and Cytarabine_.28CIA.29_Induction|Clofarabine, Idarubicin, and Cytarabine (CIA) Induction]] | ||
+ | *[[Clofarabine(Clolar)]] 15 mg/m2 IV once per day on days 1-3 | ||
+ | *[[Idarubicin (Idamycin)]]8 mg/m2 IV once per day on days 1 & 2 | ||
+ | *[[Cytarabine(Cytosar)]] 750 mg/m2 IV once per day on days 1-3 | ||
+ | |||
+ | '''3-day cycle; repeated every 3-4 weeks depending on disease response and recovery from regimen toxicity for up to six cycles''' | ||
+ | |||
+ | ===References=== | ||
+ | # Nazha A, Kantarjian H, Ravandi F, Huang X, Choi S, Garcia-Manero G, Jabbour E, Borthakur G, Kadia T, Konopleva M, Cortes J, Ferrajoli A, Kornblau S, Daver N, Pemmaraju N, Andreeff M, Estrov Z, Du M, Brandt M, Faderl S. Clofarabine, idarubicin, and cytarabine (CIA) as frontline therapy for patients ≤60 years with newly diagnosed acute myeloid leukemia. Am J Hematol. 2013 Nov;88(11):961-6. doi: 10.1002/ajh.23544. Epub 2013 Sep 9. [http://onlinelibrary.wiley.com/doi/10.1002/ajh.23544/references long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/23877926 PubMed] | ||
+ | |||
==Cytarabine & Daunorubicin== | ==Cytarabine & Daunorubicin== | ||
===Regimen, Gardin et al. 2007 (ALFA 9803)=== | ===Regimen, Gardin et al. 2007 (ALFA 9803)=== |
Revision as of 16:25, 5 November 2013
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Induction therapy
Clofarabine, Idarubicin, and Cytarabine (CIA) Induction
Regimen, Nazha et al.2013
Level of Evidence: Phase II
- Clofarabine(Clolar) 20 mg/m2 IV over 1 hour once per day on days 1-5
- Idarubicin (Idamycin) 10 mg/m2 IV over 30 minutes once per day on days 1-3
- Cytarabine(Cytosar) 1000 mg/m2 IV over 2 hours once per day on days 1-5
5-day course; patients with only partial remission underwent a second course with the same drugs, doses, and schedule
Supportive medications:
- Prophylactic levofloxacin, itraconazole, and valacyclovir were administered to all patients
- Granulocyte colony-stimulating factor neither mandated nor forbidden and given per physician discretion
Patients who achieved a CR or CRi (complete remission with incomplete platelet recovery) proceeded to Clofarabine, Idarubicin, and Cytarabine (CIA) Consolidation
References
- Nazha A, Kantarjian H, Ravandi F, Huang X, Choi S, Garcia-Manero G, Jabbour E, Borthakur G, Kadia T, Konopleva M, Cortes J, Ferrajoli A, Kornblau S, Daver N, Pemmaraju N, Andreeff M, Estrov Z, Du M, Brandt M, Faderl S. Clofarabine, idarubicin, and cytarabine (CIA) as frontline therapy for patients ≤60 years with newly diagnosed acute myeloid leukemia.Am J Hematol. 2013 Nov;88(11):961-6. doi: 10.1002/ajh.23544. Epub 2013 Sep 9. long link to original article contains verified protocol PubMed
7+3 Cytarabine & Daunorubicin ("Standard" or "conventional" dose)
Regimen #1
Level of Evidence: Phase III
- Cytarabine (Cytosar) 100 to 200 mg/m2/day IV continuous infusion on days 1 to 7
- Daunorubicin (Cerubidine) 45 mg/m2 IV once per day on days 1 to 3
7-day course
Regimen #2, Holowiecki et al. 2012
Level of Evidence: Phase III
- Cytarabine (Cytosar) 200 mg/m2/day IV continuous infusion on days 1 to 7
- Daunorubicin (Cerubidine) 60 mg/m2 IV over 5 minutes once per day on days 1 to 3
7-day course; patients with only partial remission underwent a second course with the same drugs, doses, and schedule
Supportive medications:
- "according to commonly accepted guidelines with no prophylactic IV antibiotics"
- Granulocyte colony-stimulating factor recommended only for patients >50 years old whose leukemic blasts were negative for CD114 expression
References
- Preisler H, Davis RB, Kirshner J, Dupre E, Richards F 3rd, Hoagland HC, Kopel S, Levy RN, Carey R, Schulman P et al. Comparison of three remission induction regimens and two postinduction strategies for the treatment of acute nonlymphocytic leukemia: a cancer and leukemia group B study. Blood. 1987 May;69(5):1441-9. link to original article contains verified protocol PubMed
- Rowe JM, Neuberg D, Friedenberg W, Bennett JM, Paietta E, Makary AZ, Liesveld JL, Abboud CN, Dewald G, Hayes FA, Tallman MS, Wiernik PH; Eastern Cooperative Oncology. A phase 3 study of three induction regimens and of priming with GM-CSF in older adults with acute myeloid leukemia: a trial by the Eastern Cooperative Oncology Group. Blood. 2004 Jan 15;103(2):479-85. Epub 2003 Sep 25. link to original article contains verified protocol PubMed
- Löwenberg B, Ossenkoppele GJ, van Putten W, Schouten HC, Graux C, Ferrant A, Sonneveld P, Maertens J, Jongen-Lavrencic M, von Lilienfeld-Toal M, Biemond BJ, Vellenga E, van Marwijk Kooy M, Verdonck LF, Beck J, Döhner H, Gratwohl A, Pabst T, Verhoef G; Dutch-Belgian Cooperative Trial Group for Hemato-Oncology (HOVON); German AML Study Group (AMLSG); Swiss Group for Clinical Cancer Research (SAKK) Collaborative Group. High-dose daunorubicin in older patients with acute myeloid leukemia. N Engl J Med. 2009 Sep 24;361(13):1235-48. doi: 10.1056/NEJMoa0901409. Erratum in: N Engl J Med. 2010 Mar 25;362(12):1155. Dosage error in published abstract; MEDLINE/PubMed abstract corrected; Dosage error in article text. link to original article contains verified protocol PubMed
- Fernandez HF, Sun Z, Yao X, Litzow MR, Luger SM, Paietta EM, Racevskis J, Dewald GW, Ketterling RP, Bennett JM, Rowe JM, Lazarus HM, Tallman MS. Anthracycline dose intensification in acute myeloid leukemia. N Engl J Med. 2009 Sep 24;361(13):1249-59. link to original article contains verified protocol PubMed
- Döhner H, Estey EH, Amadori S, Appelbaum FR, Büchner T, Burnett AK, Dombret H, Fenaux P, Grimwade D, Larson RA, Lo-Coco F, Naoe T, Niederwieser D, Ossenkoppele GJ, Sanz MA, Sierra J, Tallman MS, Löwenberg B, Bloomfield CD; European LeukemiaNet. Diagnosis and management of acute myeloid leukemia in adults: recommendations from an international expert panel, on behalf of the European LeukemiaNet. Blood. 2010 Jan 21;115(3):453-74. Epub 2009 Oct 30. link to original article contains verified protocol PubMed
- Holowiecki J, Grosicki S, Giebel S, Robak T, Kyrcz-Krzemien S, Kuliczkowski K, Skotnicki AB, Hellmann A, Sulek K, Dmoszynska A, Kloczko J, Jedrzejczak WW, Zdziarska B, Warzocha K, Zawilska K, Komarnicki M, Kielbinski M, Piatkowska-Jakubas B, Wierzbowska A, Wach M, Haus O. Cladribine, but not fludarabine, added to daunorubicin and cytarabine during induction prolongs survival of patients with acute myeloid leukemia: a multicenter, randomized phase III study. Journal of Clinical Oncology. 2012 Jul 10;30(20):2441-8. Epub 2012 Apr 16. link to original article contains verified protocol PubMed
7+3 Cytarabine & Daunorubicin ("High" or "escalated" dose)
Regimen #1, Fernandez et al. 2009
Level of Evidence: Phase III
- Cytarabine (Cytosar) 100 mg/m2/day IV continuous infusion on days 1 to 7
- Daunorubicin (Cerubidine) 90 mg/m2 IV once per day on days 1 to 3
7-day course
Regimen #2, Löwenberg et al. 2009 (HOVON/AMLSG/SAKK)
Level of Evidence: Phase III
- Cytarabine (Cytosar) 200 mg/m2/day IV continuous infusion on days 1 to 7
- Daunorubicin (Cerubidine) 90 mg/m2 IV once daily on days 1 to 3
7-day course
References
- Löwenberg B, Ossenkoppele GJ, van Putten W, Schouten HC, Graux C, Ferrant A, Sonneveld P, Maertens J, Jongen-Lavrencic M, von Lilienfeld-Toal M, Biemond BJ, Vellenga E, van Marwijk Kooy M, Verdonck LF, Beck J, Döhner H, Gratwohl A, Pabst T, Verhoef G; Dutch-Belgian Cooperative Trial Group for Hemato-Oncology (HOVON); German AML Study Group (AMLSG); Swiss Group for Clinical Cancer Research (SAKK) Collaborative Group. High-dose daunorubicin in older patients with acute myeloid leukemia. N Engl J Med. 2009 Sep 24;361(13):1235-48. doi: 10.1056/NEJMoa0901409. Erratum in: N Engl J Med. 2010 Mar 25;362(12):1155. Dosage error in published abstract; MEDLINE/PubMed abstract corrected; Dosage error in article text. link to original article contains verified protocol PubMed
- Fernandez HF, Sun Z, Yao X, Litzow MR, Luger SM, Paietta EM, Racevskis J, Dewald GW, Ketterling RP, Bennett JM, Rowe JM, Lazarus HM, Tallman MS. Anthracycline dose intensification in acute myeloid leukemia. N Engl J Med. 2009 Sep 24;361(13):1249-59. link to original article contains verified protocol PubMed
7+3 Cytarabine & Idarubicin
Regimen
Level of Evidence: Phase III
- Cytarabine (Cytosar) 100 to 200 mg/m2/day IV continuous infusion on days 1 to 7
- Idarubicin (Idamycin) 12 mg/m2 IV once daily on days 1 to 3
7-day course
References
- Wiernik PH, Banks PL, Case DC Jr, Arlin ZA, Periman PO, Todd MB, Ritch PS, Enck RE, Weitberg AB. Cytarabine plus idarubicin or daunorubicin as induction and consolidation therapy for previously untreated adult patients with acute myeloid leukemia. Blood. 1992 Jan 15;79(2):313-9. link to original article PubMed
- Haas R, Ho AD, Del Valle F, Fischer JT, Ehrhardt R, Döhner H, Witt B, Huberts H, Kaplan E, Hunstein W. Idarubicin/cytosine arabinoside and mitoxantrone/etoposide for the treatment of de novo acute myelogenous leukemia. Semin Oncol. 1993 Dec;20(6 Suppl 8):20-6. PubMed
- Masaoka T, Ogawa M, Yamada K, Kimura K, Ohashi Y. A phase II comparative study of idarubicin plus cytarabine versus daunorubicin plus cytarabine in adult acute myeloid leukemia. Semin Hematol. 1996 Oct;33(4 Suppl 3):12-7. PubMed
- Rowe JM, Neuberg D, Friedenberg W, Bennett JM, Paietta E, Makary AZ, Liesveld JL, Abboud CN, Dewald G, Hayes FA, Tallman MS, Wiernik PH; Eastern Cooperative Oncology. A phase 3 study of three induction regimens and of priming with GM-CSF in older adults with acute myeloid leukemia: a trial by the Eastern Cooperative Oncology Group. Blood. 2004 Jan 15;103(2):479-85. Epub 2003 Sep 25. link to original article contains verified protocol PubMed
- Döhner H, Estey EH, Amadori S, Appelbaum FR, Büchner T, Burnett AK, Dombret H, Fenaux P, Grimwade D, Larson RA, Lo-Coco F, Naoe T, Niederwieser D, Ossenkoppele GJ, Sanz MA, Sierra J, Tallman MS, Löwenberg B, Bloomfield CD; European LeukemiaNet. Diagnosis and management of acute myeloid leukemia in adults: recommendations from an international expert panel, on behalf of the European LeukemiaNet. Blood. 2010 Jan 21;115(3):453-74. Epub 2009 Oct 30. link to original article contains verified protocol PubMed
Cytarabine, Idarubicin, Sorafenib
Regimen, Ravandi et al. 2010
Level of Evidence: Phase II
Regimen details are from the phase II part of the published trial.
- Cytarabine (Cytosar) 1500 mg/m2/day IV continuous infusion on days 1 to 4
- Patients older than 60 received: Cytarabine (Cytosar) 1500 mg/m2/day IV continuous infusion on days 1 to 3
- Idarubicin (Idamycin) 12 mg/m2 IV over 1 hour once daily on days 1 to 3
- Sorafenib (Nexavar) 400 mg PO BID on days 1 to 7
7-day course, followed by Cytarabine, Idarubicin, Sorafenib consolidation therapy
References
- Ravandi F, Cortes JE, Jones D, Faderl S, Garcia-Manero G, Konopleva MY, O'Brien S, Estrov Z, Borthakur G, Thomas D, Pierce SR, Brandt M, Byrd A, Bekele BN, Pratz K, Luthra R, Levis M, Andreeff M, Kantarjian HM. Phase I/II study of combination therapy with sorafenib, idarubicin, and cytarabine in younger patients with acute myeloid leukemia. J Clin Oncol. 2010 Apr 10;28(11):1856-62. doi: 10.1200/JCO.2009.25.4888. Epub 2010 Mar 8. link to original article contains verified protocol PubMed
Cytarabine, Idarubicin, Vorinostat
Regimen, Garcia-Manero et al. 2012
Level of Evidence: Phase II
- Vorinostat (Zolinza) 500 mg PO TID on days 1 to 3
- Cytarabine (Cytosar) 1500 mg/m2/day IV continuous infusion on days 4 to 7
- Patients older than 60 received: Cytarabine (Cytosar) 1500 mg/m2/day IV continuous infusion on days 4 to 6
- Idarubicin (Idamycin) 12 mg/m2 IV once daily on days 4 to 6
7-day course x 1 to 2 cycles
Supportive medications:
- Methylprednisolone (Solumedrol) (note: the paper spelled this as "salumedrol"--it's assumed this is what they meant) 50 mg IV on days of cytarabine to prevent fever and rash
To be followed by Cytarabine, Idarubicin, Vorinostat consolidation therapy.
References
- Garcia-Manero G, Tambaro FP, Bekele NB, Yang H, Ravandi F, Jabbour E, Borthakur G, Kadia TM, Konopleva MY, Faderl S, Cortes JE, Brandt M, Hu Y, McCue D, Newsome WM, Pierce SR, de Lima M, Kantarjian HM. Phase II Trial of Vorinostat With Idarubicin and Cytarabine for Patients With Newly Diagnosed Acute Myelogenous Leukemia or Myelodysplastic Syndrome. J Clin Oncol. 2012 Jun 20;30(18):2204-10. Epub 2012 May 14. link to original article contains verified protocol PubMed
Daunorubicin, Cytarabine, Cladribine (DAC)
DAC: Daunorubicin, Ara-C, Cladribine
Regimen, Holowiecki et al. 2013
Level of Evidence: Phase III
- Daunorubicin (Cerubidine) 60 mg/m2 IV over 5 minutes once per day on days 1 to 3
- Cytarabine (Cytosar) 200 mg/m2/day IV continuous infusion on days 1 to 7
- Cladribine (Leustatin) 5 mg/m2 IV over 3 hours once per day on days 1 to 5
7-day course; patients with only partial remission underwent a second course with the same drugs, doses, and schedule
Supportive medications:
- "according to commonly accepted guidelines with no prophylactic IV antibiotics"
- Granulocyte colony-stimulating factor recommended only for patients >50 years old whose leukemic blasts were negative for CD114 expression
References
- Holowiecki J, Grosicki S, Giebel S, Robak T, Kyrcz-Krzemien S, Kuliczkowski K, Skotnicki AB, Hellmann A, Sulek K, Dmoszynska A, Kloczko J, Jedrzejczak WW, Zdziarska B, Warzocha K, Zawilska K, Komarnicki M, Kielbinski M, Piatkowska-Jakubas B, Wierzbowska A, Wach M, Haus O. Cladribine, but not fludarabine, added to daunorubicin and cytarabine during induction prolongs survival of patients with acute myeloid leukemia: a multicenter, randomized phase III study. Journal of Clinical Oncology. 2012 Jul 10;30(20):2441-8. Epub 2012 Apr 16. link to original article contains verified protocol PubMed
Decitabine monotherapy
Regimen, Blum et al. 2010
Level of Evidence: Phase II
- Decitabine (Dacogen) 20 mg/m2 IV over 1 hour once per day on days 1 to 10
28-day cycles, with additional therapy depending on response:
- Patients with persistent AML (≥5% blasts) received repeated cycles with 10 days of decitabine as described above.
- Patients with no morphologic evidence of AML (<5% blasts) received 5 days of decitabine as described by decitabine monotherapy maintenance.
Supportive medications:
- Hydroxyurea (Hydrea) allowed during and prior to cycle 1 in order to maintain WBC <40,000/L
References
- Blum W, Garzon R, Klisovic RB, Schwind S, Walker A, Geyer S, Liu S, Havelange V, Becker H, Schaaf L, Mickle J, Devine H, Kefauver C, Devine SM, Chan KK, Heerema NA, Bloomfield CD, Grever MR, Byrd JC, Villalona-Calero M, Croce CM, Marcucci G. Clinical response and miR-29b predictive significance in older AML patients treated with a 10-day schedule of decitabine. Proc Natl Acad Sci U S A. 2010 Apr 20;107(16):7473-8. doi: 10.1073/pnas.1002650107. Epub 2010 Apr 5. link to original article contains verified protocol PubMed
Decitabine & Valproate
Regimen, Garcia-Manero et al. 2006
Level of Evidence: Phase II
- Decitabine (Dacogen) 15 mg/m2 IV over 1 hour once daily on days 1 to 10
- Valproate (Depakote) 50 mg/kg/day (divided in 2 or 3 doses per day) PO on days 1 to 10
28-day cycles x up to 24 total cycles
References
- Garcia-Manero G, Kantarjian HM, Sanchez-Gonzalez B, Yang H, Rosner G, Verstovsek S, Rytting M, Wierda WG, Ravandi F, Koller C, Xiao L, Faderl S, Estrov Z, Cortes J, O'brien S, Estey E, Bueso-Ramos C, Fiorentino J, Jabbour E, Issa JP. Phase 1/2 study of the combination of 5-aza-2'-deoxycytidine with valproic acid in patients with leukemia. Blood. 2006 Nov 15;108(10):3271-9. Epub 2006 Aug 1. link to original article contains verified protocol PubMed
Idarubicin, Cytarabine, Pravastatin (IAP)
IAP: Idarubicin, Ara-C, Pravastatin
Regimen, Advani et al. 2013 (SWOG S0919)
Level of Evidence: Phase II
- Pravastatin (Pravachol) 1280 mg PO once per day on days 1 to 8
- Idarubicin (Idamycin) 12 mg/m2 IV once per day on days 4 to 6
- Cytarabine (Cytosar) 1500 mg/m2 IV once per day on days 4 to 7
Patients achieving a CR could receive 2 cycles of consolidation
References
- Anjali S. Advani, Shannon McDonough, Edward Copelan, Cheryl L. Willman, Deborah A. Mulford, Alan F. List, Mikkael A. Sekeres, Megan Othus, Harry P. Erba, Frederick R. Appelbaum. SWOG S0919: A phase II study of idarubicin and cytarabine in combination with pravastatin for relapsed acute myeloid leukemia (AML). J Clin Oncol 31, 2013 (suppl; abstr 7028). link to original article contains verified protocol
Consolidation therapy
Clofarabine, Idarubicin, and Cytarabine (CIA) Consolidation
Regimen, Nazha et al.2013
Level of Evidence: Phase II
To be preceded by Clofarabine, Idarubicin, and Cytarabine (CIA) Induction
- Clofarabine(Clolar) 15 mg/m2 IV once per day on days 1-3
- Idarubicin (Idamycin)8 mg/m2 IV once per day on days 1 & 2
- Cytarabine(Cytosar) 750 mg/m2 IV once per day on days 1-3
3-day cycle; repeated every 3-4 weeks depending on disease response and recovery from regimen toxicity for up to six cycles
References
- Nazha A, Kantarjian H, Ravandi F, Huang X, Choi S, Garcia-Manero G, Jabbour E, Borthakur G, Kadia T, Konopleva M, Cortes J, Ferrajoli A, Kornblau S, Daver N, Pemmaraju N, Andreeff M, Estrov Z, Du M, Brandt M, Faderl S. Clofarabine, idarubicin, and cytarabine (CIA) as frontline therapy for patients ≤60 years with newly diagnosed acute myeloid leukemia. Am J Hematol. 2013 Nov;88(11):961-6. doi: 10.1002/ajh.23544. Epub 2013 Sep 9. long link to original article contains verified protocol PubMed
Cytarabine & Daunorubicin
Regimen, Gardin et al. 2007 (ALFA 9803)
Level of Evidence: Phase III
Ambulatory regimen
- Cytarabine (Cytosar) 60 mg/m2 SC every 12 hours on days 1 to 5 (10 total doses)
- Daunorubicin (Cerubidine) 45 mg/m2 IV once on day 1
1-month cycles x up to 6 cycles
References
- Gardin C, Turlure P, Fagot T, Thomas X, Terre C, Contentin N, Raffoux E, de Botton S, Pautas C, Reman O, Bourhis JH, Fenaux P, Castaigne S, Michallet M, Preudhomme C, de Revel T, Bordessoule D, Dombret H. Postremission treatment of elderly patients with acute myeloid leukemia in first complete remission after intensive induction chemotherapy: results of the multicenter randomized Acute Leukemia French Association (ALFA) 9803 trial. Blood. 2007 Jun 15;109(12):5129-35. Epub 2007 Mar 6. link to original article contains verified protocol PubMed
Cytarabine, Idarubicin, Sorafenib
Regimen, Ravandi et al. 2010
Level of Evidence: Phase II
Preceded by Cytarabine, Idarubicin, Sorafenib induction therapy. Regimen details are from the phase II part of the published trial.
- Cytarabine (Cytosar) 750 mg/m2/day IV continuous infusion on days 1 to 3
- Idarubicin (Idamycin) 8 mg/m2 IV over 1 hour once on days 1 & 2
- Sorafenib (Nexavar) 400 mg PO BID "for up to 28 days"
4 to 6-week cycles x up to 5 cycles, followed by Sorafenib maintenance therapy
References
- Ravandi F, Cortes JE, Jones D, Faderl S, Garcia-Manero G, Konopleva MY, O'Brien S, Estrov Z, Borthakur G, Thomas D, Pierce SR, Brandt M, Byrd A, Bekele BN, Pratz K, Luthra R, Levis M, Andreeff M, Kantarjian HM. Phase I/II study of combination therapy with sorafenib, idarubicin, and cytarabine in younger patients with acute myeloid leukemia. J Clin Oncol. 2010 Apr 10;28(11):1856-62. doi: 10.1200/JCO.2009.25.4888. Epub 2010 Mar 8. link to original article contains verified protocol PubMed
Cytarabine, Idarubicin, Vorinostat
Regimen, Garcia-Manero et al. 2012
Level of Evidence: Phase II
Preceded by Cytarabine, Idarubicin, Vorinostat induction therapy.
- Vorinostat (Zolinza) 500 mg PO TID on days 1 to 3
- Cytarabine (Cytosar) 750 mg/m2/day IV continuous infusion on days 4 to 6
- Idarubicin (Idamycin) 8 mg/m2 IV once on days 4 & 5
6-day course x up to 5 cycles
Supportive medications:
- Methylprednisolone (Solu-Medrol) (note: the paper spelled this as "salumedrol"--it's assumed this is what they meant) 50 mg IV on days of cytarabine to prevent fever and rash
To be followed by Vorinostat (Zolinza) maintenance therapy.
References
- Garcia-Manero G, Tambaro FP, Bekele NB, Yang H, Ravandi F, Jabbour E, Borthakur G, Kadia TM, Konopleva MY, Faderl S, Cortes JE, Brandt M, Hu Y, McCue D, Newsome WM, Pierce SR, de Lima M, Kantarjian HM. Phase II Trial of Vorinostat With Idarubicin and Cytarabine for Patients With Newly Diagnosed Acute Myelogenous Leukemia or Myelodysplastic Syndrome. J Clin Oncol. 2012 Jun 20;30(18):2204-10. Epub 2012 May 14. link to original article contains verified protocol PubMed
HiDAC/HDAC, high-dose Cytarabine
HiDAC: High Dose Ara-C
Regimen
Level of Evidence: Phase III
- Cytarabine (Cytosar) 2000 to 3000 mg/m2 IV over 3 hours Q12H on days 1, 3, 5 (6 total doses)
28-day (minimum) cycles or 1 week after marrow recovery, whichever comes later, x up to 4 cycles
References
- Mayer RJ, Davis RB, Schiffer CA, Berg DT, Powell BL, Schulman P, Omura GA, Moore JO, McIntyre OR, Frei E 3rd. Intensive postremission chemotherapy in adults with acute myeloid leukemia. Cancer and Leukemia Group B. N Engl J Med. 1994 Oct 6;331(14):896-903. link to original article contains verified protocol PubMed
- Fukushima T, Urasaki Y, Yamaguchi M, Ueda M, Morinaga K, Haba T, Sugiyama T, Nakao S, Origasa H, Umehara H, Ueda T. A randomized comparison of modified intermediate-dose Ara-C versus high-dose ara-c in post-remission therapy for acute myeloid leukemia. Anticancer Res. 2012 Feb;32(2):643-7. link to original article contains verified protocol PubMed
MiDAC/MDAC, mid-dose Cytarabine
MiDAC: Mid Dose Ara-C
Regimen
Level of Evidence: Phase III
- Cytarabine (Cytosar) 1000 mg/m2 IV over 1 hour Q12H on days 1 to 5 (10 total doses)
subsequent cycles started after marrow recovery
References
- Fukushima T, Urasaki Y, Yamaguchi M, Ueda M, Morinaga K, Haba T, Sugiyama T, Nakao S, Origasa H, Umehara H, Ueda T. A randomized comparison of modified intermediate-dose Ara-C versus high-dose ara-c in post-remission therapy for acute myeloid leukemia. Anticancer Res. 2012 Feb;32(2):643-7. link to original article contains verified protocol PubMed
Maintenance therapy
Azacitidine (Vidaza)
Regimen, Grövdal et al. 2010
Level of Evidence: Phase II
Intended to be used for transformed MDS patients in remission after AML induction therapy
- Azacitidine (Vidaza) 60 mg/m2 SC daily on days 1 to 5
28-day cycles
References
- Grövdal M, Karimi M, Khan R, Aggerholm A, Antunovic P, Astermark J, Bernell P, Engström LM, Kjeldsen L, Linder O, Nilsson L, Olsson A, Holm MS, Tangen JM, Wallvik J, Oberg G, Hokland P, Jacobsen SE, Porwit A, Hellström-Lindberg E. Maintenance treatment with azacytidine for patients with high-risk myelodysplastic syndromes (MDS) or acute myeloid leukaemia following MDS in complete remission after induction chemotherapy. Br J Haematol. 2010 Aug;150(3):293-302. doi: 10.1111/j.1365-2141.2010.08235.x. Epub 2010 May 20. link to original article contains verified protocol PubMed
Decitabine monotherapy maintenance
Preceded by decitabine monotherapy induction.
Regimen, Blum et al. 2010
Level of Evidence: Phase II
Blum et al. 2010 did not clearly state whether decitabine maintenance is at the same dosage/frequency as induction therapy. This is the inferred dosage from the paper.
- Decitabine (Dacogen) 20 mg/m2 IV over 1 hour once per day on days 1 to 5
- Patients with no evidence of residual disease by flow cytometry or cytogenetics who had grade 4 neutropenia (ANC <500/uL) persisting ≥14 days received 4 days instead of 5 days of decitabine starting with the following cycle. If neutropenia occurred again as above with 4 days of decitabine, patients received 3 days instead of 4 days of decitabine starting with the following cycle.
28-day cycles, given until relapsed disease or unacceptable toxicity
References
- Blum W, Garzon R, Klisovic RB, Schwind S, Walker A, Geyer S, Liu S, Havelange V, Becker H, Schaaf L, Mickle J, Devine H, Kefauver C, Devine SM, Chan KK, Heerema NA, Bloomfield CD, Grever MR, Byrd JC, Villalona-Calero M, Croce CM, Marcucci G. Clinical response and miR-29b predictive significance in older AML patients treated with a 10-day schedule of decitabine. Proc Natl Acad Sci U S A. 2010 Apr 20;107(16):7473-8. doi: 10.1073/pnas.1002650107. Epub 2010 Apr 5. link to original article contains verified protocol PubMed
LDAC
LDAC: Low Dose Ara-C (cytarabine)
Regimen
Level of Evidence: Phase III
- Cytarabine (Cytosar) 10 mg/m2 SC BID on days 1 to 21
2-month cycles, continue until relapse
References
- Robles C, Kim KM, Oken MM, Bennett JM, Letendre L, Wiernik PH, O'Connell MJ, Cassileth PA. Low-dose cytarabine maintenance therapy vs observation after remission induction in advanced acute myeloid leukemia: an Eastern Cooperative Oncology Group Trial (E5483). Leukemia. 2000 Aug;14(8):1349-53. contains protocol PubMed
Sorafenib (Nexavar)
Regimen, Ravandi et al. 2010
Level of Evidence: Phase II
Preceded by Cytarabine, Idarubicin, Sorafenib consolidation therapy. Regimen details are from the phase II part of the published trial.
- Sorafenib (Nexavar) 400 mg PO BID
Up to one year of sorafenib therapy, including consolidation course(s)
References
- Ravandi F, Cortes JE, Jones D, Faderl S, Garcia-Manero G, Konopleva MY, O'Brien S, Estrov Z, Borthakur G, Thomas D, Pierce SR, Brandt M, Byrd A, Bekele BN, Pratz K, Luthra R, Levis M, Andreeff M, Kantarjian HM. Phase I/II study of combination therapy with sorafenib, idarubicin, and cytarabine in younger patients with acute myeloid leukemia. J Clin Oncol. 2010 Apr 10;28(11):1856-62. doi: 10.1200/JCO.2009.25.4888. Epub 2010 Mar 8. link to original article contains verified protocol PubMed
Vorinostat (Zolinza)
Regimen, Garcia-Manero et al. 2012
Level of Evidence: Phase II
Preceded by Cytarabine, Idarubicin, Vorinostat consolidation therapy.
- Vorinostat (Zolinza) 200 mg PO TID on days 1 to 14
28-day cycles x up to 12 cycles
References
- Garcia-Manero G, Tambaro FP, Bekele NB, Yang H, Ravandi F, Jabbour E, Borthakur G, Kadia TM, Konopleva MY, Faderl S, Cortes JE, Brandt M, Hu Y, McCue D, Newsome WM, Pierce SR, de Lima M, Kantarjian HM. Phase II Trial of Vorinostat With Idarubicin and Cytarabine for Patients With Newly Diagnosed Acute Myelogenous Leukemia or Myelodysplastic Syndrome. J Clin Oncol. 2012 Jun 20;30(18):2204-10. Epub 2012 May 14. link to original article contains verified protocol PubMed
Relapsed/refractory
ADE
ADE: Ara-C, Daunorubicin, Etoposide
Regimen, Milligan et al. 2006 (MRC AML-HR)
Level of Evidence: Phase III
Course 1
- Cytarabine (Cytosar) 100 mg/m2 IV push Q12H on days 1 to 10 (20 total doses)
- Daunorubicin (Cerubidine) 50 mg/m2 IV slow push once on days 1, 3, 5
- Etoposide (Vepesid) 100 mg/m2 IV over 1 hour once daily on days 1 to 5
Course 2
- Cytarabine (Cytosar) 100 mg/m2 IV push Q12H on days 1 to 8 (16 total doses)
- Daunorubicin (Cerubidine) 50 mg/m2 IV slow push once on days 1, 3, 5
- Etoposide (Vepesid) 100 mg/m2 IV over 1 hour once daily on days 1 to 5
References
- Milligan DW, Wheatley K, Littlewood T, Craig JI, Burnett AK; NCRI Haematological Oncology Clinical Studies Group. Fludarabine and cytosine are less effective than standard ADE chemotherapy in high-risk acute myeloid leukemia, and addition of G-CSF and ATRA are not beneficial: results of the MRC AML-HR randomized trial. Blood. 2006 Jun 15;107(12):4614-22. Epub 2006 Feb 16. link to original article PubMed
Azacitidine (Vidaza)
Regimen, Thepot et al. 2010
Level of Evidence: Phase II
- Azacitidine (Vidaza) 75 mg/m2 SC once daily on days 1 to 7
28-day cycles x at least 4 to 6 cycles
References
- Thepot S, Itzykson R, Seegers V, Raffoux E, Quesnel B, Chait Y, Sorin L, Dreyfus F, Cluzeau T, Delaunay J, Sanhes L, Eclache V, Dartigeas C, Turlure P, Harel S, Salanoubat C, Kiladjian JJ, Fenaux P, Adès L; Groupe Francophone des Myelodysplasies (GFM). Treatment of progression of Philadelphia-negative myeloproliferative neoplasms to myelodysplastic syndrome or acute myeloid leukemia by azacitidine: a report on 54 cases on the behalf of the Groupe Francophone des Myelodysplasies (GFM). Blood. 2010 Nov 11;116(19):3735-42. Epub 2010 Jul 27. link to original article PubMed
Azacitidine & Sorafenib
Regimen
Level of Evidence: Phase II
Majority of patients in the phase II trial were FLT-3 ITD positive
- Azacitidine (Vidaza) 75 mg/m2 SC or IV once daily on days 1 to 7
- Sorafenib (Nexavar) 400 mg PO BID
4 to 8 week cycles at treating physician's discretion
Supportive medications:
- "All patients received antimicrobials, supportive care, and transfusions of blood products according to the institutional guidelines."
References
- Ravandi F, Alattar ML, Grunwald MR, Rudek MA, Rajkhowa T, Richie MA, Pierce S, Daver N, Garcia-Manero G, Faderl S, Nazha A, Konopleva M, Borthakur G, Burger J, Kadia T, Dellasala S, Andreeff M, Cortes J, Kantarjian H, Levis M. Phase 2 study of azacytidine plus sorafenib in patients with acute myeloid leukemia and FLT-3 internal tandem duplication mutation. Blood. 2013 Jun 6;121(23):4655-62. doi:10.1182/blood-2013-01-480228. Epub 2013 Apr 23. link to original article contains verified protocol PubMed
Cladribine (Leustatin)
Regimen, Santana et al. 1992
Level of Evidence: Phase II
- Cladribine (Leustatin) 8.9 mg/m2/day IV continuous infusion on days 1 to 5
References
- Santana VM, Mirro J Jr, Kearns C, Schell MJ, Crom W, Blakley RL. 2-Chlorodeoxyadenosine produces a high rate of complete hematologic remission in relapsed acute myeloid leukemia. J Clin Oncol. 1992 Mar;10(3):364-70. link to original article PubMed
CLAG
CLAG: CLadribine, Ara-C, G-CSF
Regimen
Level of Evidence: Phase II
- Cladribine (Leustatin) 5 mg/m2 IV over 2 hours once daily on days 1 to 5, given first
- Cytarabine (Cytosar) 2000 mg/m2 IV over 4 hours once daily on days 1 to 5, given second, 2 hours after cladribine
- Filgrastim (Neupogen) 300 mcg SC once daily on days -1 to 5; first dose is given 24 hours before first dose of cladribine
References
- Robak T, Wrzesien'-Kus' A, Lech-Maran'da E, Kowal M, Dmoszyn'ska A. Combination regimen of cladribine (2-chlorodeoxyadenosine), cytarabine and G-CSF (CLAG) as induction therapy for patients with relapsed or refractory acute myeloid leukemia. Leuk Lymphoma. 2000 Sep;39(1-2):121-9. link to original article contains verified protocol PubMed
- Retrospective: Martin MG, Welch JS, Augustin K, Hladnik L, DiPersio JF, Abboud CN. Cladribine in the treatment of acute myeloid leukemia: a single-institution experience. Clin Lymphoma Myeloma. 2009 Aug;9(4):298-301. PubMed
CLAG-M, CLAM
CLAG-M: CLadribine, Ara-C, G-CSF, Mitoxantrone
Regimen
Level of Evidence: Phase II
- Cladribine (Leustatin) 5 mg/m2 IV over 2 hours once daily on days 1 to 5, given first
- Cytarabine (Cytosar) 2000 mg/m2 IV over 4 hours once daily on days 1 to 5, given second, 2 hours after cladribine
- Mitoxantrone (Novantrone) 10 mg/m2 IV once daily on days 1 to 3
- Filgrastim (Neupogen) 300 mcg SC once daily on days -1 to 5; first dose is given 24 hours before first dose of cladribine
References
- Wierzbowska A, Robak T, Pluta A, Wawrzyniak E, Cebula B, Hołowiecki J, Kyrcz-Krzemień S, Grosicki S, Giebel S, Skotnicki AB, Piatkowska-Jakubas B, Kuliczkowski K, Kiełbiński M, Zawilska K, Kłoczko J, Wrzesień-Kuś A; Polish Adult Leukemia Group. Cladribine combined with high doses of arabinoside cytosine, mitoxantrone, and G-CSF (CLAG-M) is a highly effective salvage regimen in patients with refractory and relapsed acute myeloid leukemia of the poor risk: a final report of the Polish Adult Leukemia Group. Eur J Haematol. 2008 Feb;80(2):115-26. Epub 2007 Dec 11. link to original article PubMed content property of HemOnc.org
- Retrospective: Martin MG, Welch JS, Augustin K, Hladnik L, DiPersio JF, Abboud CN. Cladribine in the treatment of acute myeloid leukemia: a single-institution experience. Clin Lymphoma Myeloma. 2009 Aug;9(4):298-301. PubMed
Clofarabine & Cytarabine
Regimen #1, Agura, et al., 2011
Level of Evidence: Phase II
- Clofarabine (Clolar) 40 mg/m2 IV over 1 hour once daily on days 1 to 5, given first
- Cytarabine (Cytosar) 1000 mg/m2 IV over 2 hours once daily on days 1 to 5, given second, 4 hours after completion of clofarabine infusion
up to 4 total cycles; subsequent cycles start after hematologic recovery from the previous cycle and were recommended for patients who had hematologic response, but not complete response (CR)
Supportive medications:
- Dexamethasone (Decadron) 10 mg IV once daily
- 5-HT3 antagonists on each day of chemotherapy
- Hydration at 150 mL/m2/H "to prevent tumor lysis syndrome" during chemotherapy
- Bumetanide (Bumex) 2 to 4 mg IV push once to twice daily as needed to keep weight within 1 kg of patient's initial weight
- Levofloxacin (Levaquin) 500 mg PO/IV once daily
- Acyclovir (Zovirax) 500 mg IV Q12H
- One of the following antifungals:
- Caspofungin (Cancidas) 50 mg IV once daily
- Voriconazole (VFEND) 200 mg (route not specified) BID
- Parenteral nutrition allowed
- No routine use of growth factors
Regimen #2, Faderl, et al., 2012 (CLASSIC I)
Level of Evidence: Phase III
- Clofarabine (Clolar) 40 mg/m2 IV over 1 hour once daily on days 1 to 5, given first
- Cytarabine (Cytosar) 1000 mg/m2 IV over 2 hours once daily on days 1 to 5, given second, 3 hours after completion of clofarabine infusion
1 to 3 cycles; It was not clear if the consolidation cycle mentioned here would also be clofarabine and cytarabine or something else: "Patients who achieved remission after their induction cycle could receive a single (optional) consolidation cycle; patients who did not achieve remission after induction but who demonstrated hematologic improvement could receive a reinduction cycle followed by a single (optional) consolidation cycle."
Supportive medications:
- "The use of prophylactic antibacterial, antifungal, and antiviral agents was recommended according to institutional guidelines."
References
- Agura E, Cooper B, Holmes H, Vance E, Berryman RB, Maisel C, Li S, Saracino G, Tadic-Ovcina M, Fay J. Report of a phase II study of clofarabine and cytarabine in de novo and relapsed and refractory AML patients and in selected elderly patients at high risk for anthracycline toxicity. Oncologist. 2011;16(2):197-206. doi: 10.1634/theoncologist.2010-0220. Epub 2011 Jan 27. link to original article contains verified protocol PubMed
- Faderl S, Wetzler M, Rizzieri D, Schiller G, Jagasia M, Stuart R, Ganguly S, Avigan D, Craig M, Collins R, Maris M, Kovacsovics T, Goldberg S, Seiter K, Hari P, Greiner J, Vey N, Recher C, Ravandi F, Wang ES, Vasconcelles M, Huebner D, Kantarjian HM. Clofarabine plus cytarabine compared with cytarabine alone in older patients with relapsed or refractory acute myelogenous leukemia: results from the CLASSIC I Trial. J Clin Oncol. 2012 Jul 10;30(20):2492-9. doi:10.1200/JCO.2011.37.9743. Epub 2012 May 14. link to original article contains verified protocol PubMed
Cytarabine (Cytosar)
Regimen, Faderl, et al., 2012 (CLASSIC I)
Level of Evidence: Phase III
- Cytarabine (Cytosar) 1000 mg/m2 IV over 2 hours once daily on days 1 to 5
1 to 3 cycles; It was not clear if the consolidation cycle mentioned here would also be cytarabine or something else: "Patients who achieved remission after their induction cycle could receive a single (optional) consolidation cycle; patients who did not achieve remission after induction but who demonstrated hematologic improvement could receive a reinduction cycle followed by a single (optional) consolidation cycle."
Supportive medications:
- "The use of prophylactic antibacterial, antifungal, and antiviral agents was recommended according to institutional guidelines."
References
- Faderl S, Wetzler M, Rizzieri D, Schiller G, Jagasia M, Stuart R, Ganguly S, Avigan D, Craig M, Collins R, Maris M, Kovacsovics T, Goldberg S, Seiter K, Hari P, Greiner J, Vey N, Recher C, Ravandi F, Wang ES, Vasconcelles M, Huebner D, Kantarjian HM. Clofarabine plus cytarabine compared with cytarabine alone in older patients with relapsed or refractory acute myelogenous leukemia: results from the CLASSIC I Trial. J Clin Oncol. 2012 Jul 10;30(20):2492-9. doi:10.1200/JCO.2011.37.9743. Epub 2012 May 14. link to original article contains verified protocol PubMed
Decitabine (Dacogen)
Regimen, Kantarjian et al. 2012
Level of Evidence: Phase III
- Decitabine (Dacogen) 20 mg/m2 IV over 1 hour once daily on days 1 to 5
28-day cycles, given until progression of disease or unacceptable toxicity
Supportive medications:
- Hydroxyurea (Hydrea) could be used up until cycle 1 day 15.
References
- Kantarjian HM, Thomas XG, Dmoszynska A, Wierzbowska A, Mazur G, Mayer J, Gau JP, Chou WC, Buckstein R, Cermak J, Kuo CY, Oriol A, Ravandi F, Faderl S, Delaunay J, Lysák D, Minden M, Arthur C. Multicenter, randomized, open-label, phase III trial of decitabine versus patient choice, with physician advice, of either supportive care or low-dose cytarabine for the treatment of older patients with newly diagnosed acute myeloid leukemia. J Clin Oncol. 2012 Jul 20;30(21):2670-7. doi: 10.1200/JCO.2011.38.9429. Epub 2012 Jun 11. link to original article contains verified protocol PubMed
FLAG
FLAG: FLudarabine, Ara-C, G-CSF
Regimen, Montillo et al. 1998
Level of Evidence: Phase II
- Fludarabine (Fludara) 30 mg/m2 IV over 30 minutes once daily on days 1 to 5, given first
- Cytarabine (Cytosar) 2000 mg/m2 IV over 4 hours once daily on days 1 to 5, given second, 4 hours after the start of fludarabine
- Filgrastim (Neupogen) or Lenograstim (Granocyte) 5 mcg/kg SC once daily starting on day -1 (the paper described this as "day 0"), first dose given 24 hours before first dose of chemotherapy, to continue until neutrophil recovery
References
- Montillo M, Mirto S, Petti MC, Latagliata R, Magrin S, Pinto A, Zagonel V, Mele G, Tedeschi A, Ferrara F. Fludarabine, cytarabine, and G-CSF (FLAG) for the treatment of poor risk acute myeloid leukemia. Am J Hematol. 1998 Jun;58(2):105-9. link to original article contains verified protocol PubMed
FLAG-IDA
FLAG-IDA: FLudarabine, Ara-C, G-CSF, IDArubicin
Regimen
Level of Evidence: Phase II
- Fludarabine (Fludara) 30 mg/m2 IV over 30 minutes once daily on days 1 to 5, given first
- Cytarabine (Cytosar) 2000 mg/m2 IV over 4 hours once daily on days 1 to 5, given second, 4 hours after fludarabine
- Idarubicin (Idamycin) 10 mg/m2 IV once daily on days 1 to 3
- Filgrastim (Neupogen) 5 mcg/kg SC once daily starting on day 6, to continue until neutrophil recovery
References
- Parker JE, Pagliuca A, Mijovic A, Cullis JO, Czepulkowski B, Rassam SM, Samaratunga IR, Grace R, Gover PA, Mufti GJ. Fludarabine, cytarabine, G-CSF and idarubicin (FLAG-IDA) for the treatment of poor-risk myelodysplastic syndromes and acute myeloid leukaemia. Br J Haematol. 1997 Dec;99(4):939-44. PubMed
- Pastore D, Specchia G, Carluccio P, Liso A, Mestice A, Rizzi R, Greco G, Buquicchio C, Liso V. FLAG-IDA in the treatment of refractory/relapsed acute myeloid leukemia: single-center experience. Ann Hematol. 2003 Apr;82(4):231-5. Epub 2003 Mar 15. link to original article PubMed
Mitoxantrone & Cytarabine
Regimen, Sternberg et al. 2000
Level of Evidence: Phase II
- Mitoxantrone (Novantrone) 5 mg/m2 IV bolus once daily on days 1 to 5
- Cytarabine (Cytosar) 500 mg/m2 IV over 90 minutes every 12 hours on days 1 to 6 (12 total doses)
References
- Sternberg DW, Aird W, Neuberg D, Thompson L, MacNeill K, Amrein P, Shulman LN. Treatment of patients with recurrent and primary refractory acute myelogenous leukemia using mitoxantrone and intermediate-dose cytarabine: a pharmacologically based regimen. Cancer. 2000 May 1;88(9):2037-41. link to original article contains verified protocol PubMed
Mitoxantrone & Etoposide
Regimen, Ho et al. 1988
Level of Evidence: Phase II
- Mitoxantrone (Novantrone) 10 mg/m2 IV over 15 minutes once daily on days 1 to 5
- Etoposide (Vepesid) 100 mg/m2 IV over 30 minutes once daily on days 1 to 5
References
- Ho AD, Lipp T, Ehninger G, Illiger HJ, Meyer P, Freund M, Hunstein W. Combination of mitoxantrone and etoposide in refractory acute myelogenous leukemia--an active and well-tolerated regimen. J Clin Oncol. 1988 Feb;6(2):213-7. link to original article PubMed
MEC
MEC: Mitoxantrone, Etoposide, Cytarabine
Regimen #1, Amadori et al. 1991
Level of Evidence: Phase II
- Mitoxantrone (Novantrone) 6 mg/m2 IV bolus once daily on days 1 to 6
- Etoposide (Vepesid) 80 mg/m2 IV over 1 hour once daily on days 1 to 6
- Cytarabine (Cytosar) 1000 mg/m2 IV over 6 hours once daily on days 1 to 6
Regimen #2, Kohrt et al. 2010
Level of Evidence: Retrospective
- Mitoxantrone (Novantrone) 8 mg/m2 IV push once daily on days 1 to 5, given third
- Etoposide (Vepesid) 100 mg/m2 IV over 2 hours once daily on days 1 to 5, given first
- Cytarabine (Cytosar) 1000 mg/m2 IV once daily on days 1 to 5, given second
References
- Amadori S, Arcese W, Isacchi G, Meloni G, Petti MC, Monarca B, Testi AM, Mandelli F. Mitoxantrone, etoposide, and intermediate-dose cytarabine: an effective and tolerable regimen for the treatment of refractory acute myeloid leukemia. J Clin Oncol. 1991 Jul;9(7):1210-4. link to original article PubMed
- Kohrt HE, Patel S, Ho M, Owen T, Pollyea DA, Majeti R, Gotlib J, Coutre S, Liedtke M, Berube C, Alizadeh AA, Medeiros BC. Second-line mitoxantrone, etoposide, and cytarabine for acute myeloid leukemia: a single-center experience. Am J Hematol. 2010 Nov;85(11):877-81. link to original article contains verified protocol PubMed