|
|
| Line 6: |
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| | |- | | |- |
| | |} | | |} |
| − | <big>'''Note: biomarker-specific regimens have been moved to dedicated pages:''' | + | <big>'''Note: these are biomarker-specific regimens for patients with FLT3 internal tandem duplicated (FLT3-ITD) or tyrosine kinase domain mutated (FLT3-TKD) AML, please see the [[Acute myeloid leukemia|main AML page]] for other regimens.'''</big> |
| − | *'''[[Acute_myeloid_leukemia,_FLT3-positive|AML, FLT3-positive]]'''
| + | |
| − | *'''[[Acute_myeloid_leukemia,_IDH-mutated|AML, IDH-mutated]]'''
| |
| − | </big> | |
| | {| class="wikitable" style="float:right; margin-right: 5px;" | | {| class="wikitable" style="float:right; margin-right: 5px;" |
| | |- | | |- |
| Line 17: |
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| | {{TOC limit|limit=3}} | | {{TOC limit|limit=3}} |
| | | | |
| − | =Guidelines= | + | =Upfront induction therapy, standard patients= |
| − | ==ELN== | + | ==7+3d & Midostaurin {{#subobject:b7ea7e|Regimen=1}}== |
| − | ====Current====
| + | {{#subobject:fef011|Variant=1}} |
| − | *'''2017:''' [http://www.bloodjournal.org/content/129/4/424.long Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5291965/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/27895058 PubMed]
| + | {{:Cytarabine, Daunorubicin, and Midostaurin induction therapy for acute myeloid leukemia (AML)}} |
| − | ====Older====
| |
| − | *'''2010:''' [http://www.bloodjournal.org/content/115/3/453.long Diagnosis and management of acute myeloid leukemia in adults: recommendations from an international expert panel, on behalf of the European LeukemiaNet] [https://www.ncbi.nlm.nih.gov/pubmed/19880497 PubMed]
| |
| − | | |
| − | ==[http://www.esmo.org/ ESMO]==
| |
| − | *'''2013:''' [http://annonc.oxfordjournals.org/content/24/suppl_6/vi138.full.pdf+html Acute myeloblastic leukaemias in adult patients: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up] [https://www.ncbi.nlm.nih.gov/pubmed/23970018 PubMed]
| |
| − | | |
| − | ==[https://www.nccn.org/ NCCN]==
| |
| − | *[https://www.nccn.org/professionals/physician_gls/pdf/aml.pdf NCCN Guidelines - Acute Myeloid Leukemia]
| |
| | | | |
| − | =Upfront induction therapy, standard and older "fit" patients= | + | =First-line induction therapy, older patients or "unfit" patients= |
| − | ''These are aggressive remission induction regimens given with curative intent.''
| + | ==7+3d & Sorafenib {{#subobject:6ad412|Regimen=1}}== |
| − | ==5+3d {{#subobject:81c0c6|Regimen=1}}== | |
| | {| class="wikitable" style="float:right; margin-left: 5px;" | | {| class="wikitable" style="float:right; margin-left: 5px;" |
| | |- | | |- |
| | |[[#top|back to top]] | | |[[#top|back to top]] |
| | |} | | |} |
| − | 5+3d: '''<u>5</u>''' days of cytarabine + '''<u>3</u>''' days of '''<u>d</u>'''aunorubicin
| |
| − | ===Regimen {{#subobject:efdecc|Variant=1}}===
| |
| − | {| class="wikitable" style="width: 100%; text-align:center;"
| |
| − | !Study
| |
| − | ![[Levels_of_Evidence#Evidence|Evidence]]
| |
| − | !Comparator
| |
| − | ![[Levels_of_Evidence#Efficacy|Efficacy]]
| |
| − | |-
| |
| − | |[http://www.bloodjournal.org/content/77/8/1666.long Berman et al. 1991 (L-19 Protocol)]
| |
| − | | style="background-color:#1a9851" |Phase III (C)
| |
| − | |[[#5.2B3i|5+3i]]
| |
| − | | style="background-color:#d73027" |Inferior CR rate
| |
| − | |-
| |
| − | |}
| |
| − | ====Chemotherapy====
| |
| − | *[[Cytarabine (Cytosar)]] 25 mg/m<sup>2</sup> IV bolus, followed by 200 mg/m<sup>2</sup>/day IV continuous infusion on days 1 to 5
| |
| − | *[[Daunorubicin (Cerubidine)]] 50 mg/m<sup>2</sup> IV once per day on days 1 to 3
| |
| | | | |
| − | '''5-day course'''
| + | ===Regimen {{#subobject:c95c56|Variant=1}}=== |
| − | | |
| − | ===References===
| |
| − | # '''L-19 Protocol:''' Berman E, Heller G, Santorsa J, McKenzie S, Gee T, Kempin S, Gulati S, Andreeff M, Kolitz J, Gabrilove J, Reich L, Mayer K, Keefe D, Trainor K, Schluger A, Penenberg D, Raymond V, O'Reilly R, Jhanwar S, Young C, Clarkson B. Results of a randomized trial comparing idarubicin and cytosine arabinoside with daunorubicin and cytosine arabinoside in adult patients with newly diagnosed acute myelogenous leukemia. Blood. 1991 Apr 15;77(8):1666-74. [http://www.bloodjournal.org/content/77/8/1666.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/2015395 PubMed]
| |
| − | | |
| − | ==5+3i {{#subobject:968e9b|Regimen=1}}==
| |
| − | {| class="wikitable" style="float:right; margin-left: 5px;"
| |
| − | |-
| |
| − | |[[#top|back to top]]
| |
| − | |}
| |
| − | 5+3i: '''<u>5</u>''' days of cytarabine + '''<u>3</u>''' days of '''<u>i</u>'''darubicin
| |
| − | ===Regimen {{#subobject:ba00c1|Variant=1}}=== | |
| | {| class="wikitable" style="width: 100%; text-align:center;" | | {| class="wikitable" style="width: 100%; text-align:center;" |
| | !Study | | !Study |
| | ![[Levels_of_Evidence#Evidence|Evidence]] | | ![[Levels_of_Evidence#Evidence|Evidence]] |
| − | !Comparator
| |
| − | ![[Levels_of_Evidence#Efficacy|Efficacy]]
| |
| | |- | | |- |
| − | |[http://www.bloodjournal.org/content/77/8/1666.long Berman et al. 1991 (L-19 Protocol)]
| + | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5637402/ Uy et al. 2017 (CALGB 11001)] |
| − | | style="background-color:#1a9851" |Phase III (E)
| + | | style="background-color:#91cf61" |Phase II |
| − | |[[#5.2B3d|5+3d]]
| |
| − | | style="background-color:#1a9850" |Superior CR rate
| |
| − | |-
| |
| − | |}
| |
| − | ====Chemotherapy====
| |
| − | *[[Cytarabine (Cytosar)]] 25 mg/m<sup>2</sup> IV bolus, followed by 200 mg/m<sup>2</sup>/day IV continuous infusion on days 1 to 5
| |
| − | *[[Idarubicin (Idamycin)]] 12 mg/m<sup>2</sup> IV bolus once per day on days 1 to 3
| |
| − | | |
| − | '''5-day course'''
| |
| − | | |
| − | ===References===
| |
| − | # '''L-19 Protocol:''' Berman E, Heller G, Santorsa J, McKenzie S, Gee T, Kempin S, Gulati S, Andreeff M, Kolitz J, Gabrilove J, Reich L, Mayer K, Keefe D, Trainor K, Schluger A, Penenberg D, Raymond V, O'Reilly R, Jhanwar S, Young C, Clarkson B. Results of a randomized trial comparing idarubicin and cytosine arabinoside with daunorubicin and cytosine arabinoside in adult patients with newly diagnosed acute myelogenous leukemia. Blood. 1991 Apr 15;77(8):1666-74. [http://www.bloodjournal.org/content/77/8/1666.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/2015395 PubMed]
| |
| − | | |
| − | ==7+3d (standard-dose) {{#subobject:9f31ad|Regimen=1}}==
| |
| − | {| class="wikitable" style="float:right; margin-left: 5px;"
| |
| − | |-
| |
| − | |[[#top|back to top]]
| |
| − | |}
| |
| − | 7+3d: '''<u>7</u>''' days of cytarabine + '''<u>3</u>''' days of '''<u>d</u>'''aunorubicin
| |
| − | <br>AD: '''<u>A</u>'''ra-C (Cytarabine) & '''<u>D</u>'''aunorubicin
| |
| − | <br>DA: '''<u>D</u>'''aunorubicin & '''<u>A</u>'''ra-C (Cytarabine)
| |
| − | ===Variant #1, CI Ara-C (100 mg/m<sup>2</sup>) {{#subobject:bb27bc|Variant=1}}===
| |
| − | {| class="wikitable" style="width: 100%; text-align:center;"
| |
| − | !Study
| |
| − | ![[Levels_of_Evidence#Evidence|Evidence]]
| |
| − | !Comparator
| |
| − | ![[Levels_of_Evidence#Efficacy|Efficacy]]
| |
| − | |-
| |
| − | | rowspan="3" |[http://www.bloodjournal.org/content/58/6/1203.long Rai et al. 1981 (CALGB 7421)]
| |
| − | | rowspan="3" style="background-color:#1a9851" |Phase III (E)
| |
| − | |7+3d (bolus Ara-C)
| |
| − | | style="background-color:#91cf60" |Seems to have superior CR rate
| |
| − | |-
| |
| − | |5+2d
| |
| − | | style="background-color:#1a9850" |Superior CR rate
| |
| − | |-
| |
| − | |5+2d (bolus Ara-C)
| |
| − | | style="background-color:#1a9850" |Superior CR rate
| |
| − | |-
| |
| − | | rowspan="2" |[http://www.bloodjournal.org/content/60/2/454.long Yates et al. 1982 (CALGB 7721)]
| |
| − | | rowspan="2" style="background-color:#1a9851" |Phase III (C)
| |
| − | |7+3d, low-dose dauno (30 mg/m<sup>2</sup>)
| |
| − | | style="background-color:#ffffbf" |Seems not superior
| |
| − | |-
| |
| − | |7+3a (30 mg/m<sup>2</sup>)
| |
| − | | style="background-color:#ffffbf" |Seems not superior
| |
| − | |-
| |
| − | | rowspan="2" |[http://www.bloodjournal.org/content/69/5/1441.long Preisler et al. 1987 (CALGB 7921)]
| |
| − | | rowspan="2" style="background-color:#1a9851" |Phase III (C)
| |
| − | |10+3d
| |
| − | | style="background-color:#ffffbf" |Seems not superior
| |
| − | |-
| |
| − | |TAD
| |
| − | | style="background-color:#ffffbf" |Seems not superior
| |
| − | |-
| |
| − | |[http://www.bloodjournal.org/content/79/2/313 Wiernik et al. 1992]
| |
| − | | style="background-color:#1a9851" |Phase III (C)
| |
| − | |[[#7.2B3i|7+3i]]
| |
| − | | style="background-color:#fc8d59" |Seems to have inferior OS
| |
| − | |-
| |
| − | |[http://www.bloodjournal.org/content/103/2/479.long Rowe et al. 2004]
| |
| − | | style="background-color:#1a9851" |Phase III (C)
| |
| − | |7+3d + GM-CSF<br> [[#7.2B3i|7+3i]]<br> 7+3i + GM-CSF<br> [[#7.2B3m|7+3m]]<br> 7+3m + GM-CSF
| |
| − | | style="background-color:#ffffbf" |Seems not superior
| |
| − | |-
| |
| − | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4480917/ Fernandez et al. 2009 (ECOG E1900)] | |
| − | | style="background-color:#1a9851" |Phase III (C)
| |
| − | |[[#7.2B3d_.28high-dose.29|7+3d (high-dose)]]
| |
| − | | style="background-color:#d73027" |Inferior OS
| |
| − | |-
| |
| − | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4504945/ Dombret et al. 2015 (AZA-AML-001)]
| |
| − | | style="background-color:#1a9851" |Phase III (C)
| |
| − | |[[#Azacitidine_monotherapy|Azacitidine]]
| |
| − | | style="background-color:#fee08b" |Might have inferior OS
| |
| − | |-
| |
| − | |}
| |
| − | ''Note: this was the lower bound of the allowable daunorubicin dose in AZA-AML-001.''
| |
| − | ====Chemotherapy====
| |
| − | *[[Cytarabine (Cytosar)]] 100 mg/m<sup>2</sup>/day IV continuous infusion on days 1 to 7 (total dose: 700 mg/m<sup>2</sup>)
| |
| − | *[[Daunorubicin (Cerubidine)]] 45 mg/m<sup>2</sup> IV once per day on days 1 to 3
| |
| − | | |
| − | '''7-day course'''
| |
| − | ====Subsequent treatment====
| |
| − | *Rowe et al. 2004: Patients with persistent disease at day 14 (greater than 5% blasts) underwent an identical second cycle of 7+3i
| |
| − | | |
| − | ===Variant #2, CI Ara-C (200 mg/m<sup>2</sup>) {{#subobject:635ecb|Variant=1}}===
| |
| − | {| class="wikitable" style="width: 100%; text-align:center;"
| |
| − | !Study
| |
| − | ![[Levels_of_Evidence#Evidence|Evidence]]
| |
| − | !Comparator
| |
| − | ![[Levels_of_Evidence#Efficacy|Efficacy]]
| |
| − | |-
| |
| − | |[http://www.bloodjournal.org/content/88/8/2841.long Weick et al. 1996]
| |
| − | | style="background-color:#1a9851" |Phase III (C)
| |
| − | |HDAC+3d
| |
| − | | style="background-color:#ffffbf" |Seems not superior
| |
| − | |-
| |
| − | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1895015/ Moore et al. 2004 (CALGB 9222)]
| |
| − | | style="background-color:#91cf61" |Non-randomized portion of RCT | |
| − | | style="background-color:#d3d3d3" |
| |
| − | | style="background-color:#d3d3d3" |
| |
| − | |-
| |
| − | |[http://www.nejm.org/doi/full/10.1056/NEJMoa0901409 Löwenberg et al. 2009 (HOVON 43 AML/SAKK 30/01)]
| |
| − | | style="background-color:#1a9851" |Phase III (C)
| |
| − | |[[#7.2B3d_.28high-dose.29|7+3d (high-dose)]]
| |
| − | | style="background-color:#d73027" |Inferior CR rate
| |
| − | |-
| |
| − | |[http://jco.ascopubs.org/content/33/11/1252.full Stone et al. 2015 (ACCEDE)]
| |
| − | | style="background-color:#1a9851" |Phase III (C)
| |
| − | |Amonafide & Cytarabine
| |
| − | | style="background-color:#ffffbf" |Seems not superior
| |
| − | |-
| |
| − | |}
| |
| − | ====Chemotherapy====
| |
| − | *[[Cytarabine (Cytosar)]] 200 mg/m<sup>2</sup>/day IV continuous infusion on days 1 to 7 (total dose: 1400 mg/m<sup>2</sup>)
| |
| − | *[[Daunorubicin (Cerubidine)]] 45 mg/m<sup>2</sup> IV once per day on days 1 to 3
| |
| − | | |
| − | '''7-day course'''
| |
| − | ====Subsequent treatment====
| |
| − | *CALGB 9222: [[#HiDAC|HiDAC]] versus multi-agent chemotherapy consolidation
| |
| − | *HOVON 43 AML/SAKK 30/01: [[#IDAC|MiDAC consolidation]]
| |
| − | *ACCEDE: patients received a second course of the same regimen if their day 14 bone marrow was positive. Patients with PR or better at time of count recovery received allogeneic stem cell transplant if eligible, otherwise [[#HiDAC|HiDAC]] if younger than 60 or [[#IDAC|MiDAC]] if greater than or equal to 60.
| |
| − | | |
| − | ===Variant #3, intermittent Ara-C {{#subobject:1f1bb5|Variant=1}}===
| |
| − | {| class="wikitable" style="width: 100%; text-align:center;"
| |
| − | !Study
| |
| − | ![[Levels_of_Evidence#Evidence|Evidence]]
| |
| − | !Comparator
| |
| − | ![[Levels_of_Evidence#Efficacy|Efficacy]]
| |
| − | |-
| |
| − | |[https://www.ncbi.nlm.nih.gov/pubmed/8916311 Masaoka et al. 1996]
| |
| − | | style="background-color:#1a9851" |Randomized Phase II (E)
| |
| − | |[[#7.2B3i|7+3i]]
| |
| − | | style="background-color:#fc8d59" |Seems to have inferior CR rate
| |
| − | |-
| |
| − | |}
| |
| − | ====Chemotherapy====
| |
| − | *[[Cytarabine (Cytosar)]] 80 mg/m<sup>2</sup> IV over 2 hours q12h on days 1 to 7
| |
| − | *[[Daunorubicin (Cerubidine)]] 40 mg/m<sup>2</sup> IV bolus once per day on days 1 to 3
| |
| − | | |
| − | '''7-day course'''
| |
| − | | |
| − | ===References===
| |
| − | # '''CALGB 7421:''' Rai KR, Holland JF, Glidewell OJ, Weinberg V, Brunner K, Obrecht JP, Preisler HD, Nawabi IW, Prager D, Carey RW, Cooper MR, Haurani F, Hutchison JL, Silver RT, Falkson G, Wiernik P, Hoagland HC, Bloomfield CD, James GW, Gottlieb A, Ramanan SV, Blom J, Nissen NI, Bank A, Ellison RR, Kung F, Henry P, McIntyre OR, Kaan SK. Treatment of acute myelocytic leukemia: a study by Cancer and Leukemia Group B. Blood. 1981 Dec;58(6):1203-12. [http://www.bloodjournal.org/content/58/6/1203.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/6946847 PubMed]
| |
| − | # '''CALGB 7721:''' Yates J, Glidewell O, Wiernik P, Cooper MR, Steinberg D, Dosik H, Levy R, Hoagland C, Henry P, Gottlieb A, Cornell C, Berenberg J, Hutchison JL, Raich P, Nissen N, Ellison RR, Frelick R, James GW, Falkson G, Silver RT, Haurani F, Green M, Henderson E, Leone L, Holland JF. Cytosine arabinoside with daunorubicin or adriamycin for therapy of acute myelocytic leukemia: a CALGB study. Blood. 1982 Aug;60(2):454-62. [http://www.bloodjournal.org/content/60/2/454.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/6953986 PubMed]
| |
| − | # '''CALGB 7921:''' Preisler H, Davis RB, Kirshner J, Dupre E, Richards F 3rd, Hoagland HC, Kopel S, Levy RN, Carey R, Schulman P, Gottlieb AJ, McIntyre OR. 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. [http://www.bloodjournal.org/content/69/5/1441.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/3552076 PubMed]
| |
| − | # 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. [http://www.bloodjournal.org/content/79/2/313 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/1730080 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. '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/8916311 PubMed]
| |
| − | # Weick JK, Kopecky KJ, Appelbaum FR, Head DR, Kingsbury LL, Balcerzak SP, Bickers JN, Hynes HE, Welborn JL, Simon SR, Grever M. A randomized investigation of high-dose versus standard-dose cytosine arabinoside with daunorubicin in patients with previously untreated acute myeloid leukemia: a Southwest Oncology Group study. Blood. 1996 Oct 15;88(8):2841-51. [http://www.bloodjournal.org/content/88/8/2841.long link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/8874180 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. [http://www.bloodjournal.org/content/103/2/479.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/14512295 PubMed]
| |
| − | # '''CALGB 9222:''' Moore JO, George SL, Dodge RK, Amrein PC, Powell BL, Kolitz JE, Baer MR, Davey FR, Bloomfield CD, Larson RA, Schiffer CA. Sequential multiagent chemotherapy is not superior to high-dose cytarabine alone as postremission intensification therapy for acute myeloid leukemia in adults under 60 years of age: Cancer and Leukemia Group B Study 9222. Blood. 2005 May 1;105(9):3420-7. Epub 2004 Nov 30. [http://www.bloodjournal.org/content/105/9/3420.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1895015/ link to PMC article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/15572587 PubMed]
| |
| − | # '''HOVON 43 AML/SAKK 30/01:''' 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. 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. [http://www.nejm.org/doi/full/10.1056/NEJMoa0901409 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/19776405 PubMed]
| |
| − | # '''ECOG E1900:''' 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. [http://www.nejm.org/doi/full/10.1056/NEJMoa0904544 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4480917/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/19776406 PubMed]
| |
| − | ## '''Update:''' Luskin MR, Lee JW, Fernandez HF, Abdel-Wahab O, Bennett JM, Ketterling RP, Lazarus HM, Levine RL, Litzow MR, Paietta EM, Patel JP, Racevskis J, Rowe JM, Tallman MS, Sun Z, Luger SM. Benefit of high-dose daunorubicin in AML induction extends across cytogenetic and molecular groups. Blood. 2016 Mar 24;127(12):1551-8. Epub 2016 Jan 11. [http://www.bloodjournal.org/content/127/12/1551.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4807422/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/26755712 PubMed]
| |
| − | # '''ACCEDE:''' Stone RM, Mazzola E, Neuberg D, Allen SL, Pigneux A, Stuart RK, Wetzler M, Rizzieri D, Erba HP, Damon L, Jang JH, Tallman MS, Warzocha K, Masszi T, Sekeres MA, Egyed M, Horst HA, Selleslag D, Solomon SR, Venugopal P, Lundberg AS, Powell B. Phase III open-label randomized study of cytarabine in combination with amonafide l-malate or daunorubicin as induction therapy for patients with secondary acute myeloid leukemia. J Clin Oncol. 2015 Apr 10;33(11):1252-7. Epub 2015 Mar 2. [http://jco.ascopubs.org/content/33/11/1252.full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/25732165 PubMed]
| |
| − | # '''AZA-AML-001:''' Dombret H, Seymour JF, Butrym A, Wierzbowska A, Selleslag D, Jang JH, Kumar R, Cavenagh J, Schuh AC, Candoni A, Récher C, Sandhu I, Bernal Del Castillo T, Al-Ali HK, Martinelli G, Falantes J, Noppeney R, Stone RM, Minden MD, McIntyre H, Songer S, Lucy LM, Beach CL, Döhner H. International phase 3 study of azacitidine vs conventional care regimens in older patients with newly diagnosed AML with >30% blasts. Blood. 2015 Jul 16;126(3):291-9. Epub 2015 May 18. [http://www.bloodjournal.org/content/126/3/291.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4504945/ link to PMC article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/25987659 PubMed]
| |
| − | ## '''Subgroup analysis:''' Seymour JF, Döhner H, Butrym A, Wierzbowska A, Selleslag D, Jang JH, Kumar R, Cavenagh J, Schuh AC, Candoni A, Récher C, Sandhu I, Del Castillo TB, Al-Ali HK, Falantes J, Stone RM, Minden MD, Weaver J, Songer S, Beach CL, Dombret H. Azacitidine improves clinical outcomes in older patients with acute myeloid leukaemia with myelodysplasia-related changes compared with conventional care regimens. BMC Cancer. 2017 Dec 14;17(1):852. [https://bmccancer.biomedcentral.com/articles/10.1186/s12885-017-3803-6 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5731212/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/29241450 PubMed]
| |
| − | | |
| − | ==7+3d (intermediate-dose) {{#subobject:e82156|Regimen=1}}==
| |
| − | {| class="wikitable" style="float:right; margin-left: 5px;"
| |
| − | |-
| |
| − | |[[#top|back to top]]
| |
| − | |}
| |
| − | 7+3d: '''<u>7</u>''' days of cytarabine + '''<u>3</u>''' days of '''<u>d</u>'''aunorubicin
| |
| − | ===Variant #1, CI Ara-C (100 mg/m<sup>2</sup>) {{#subobject:bb27bc|Variant=1}}===
| |
| − | {| class="wikitable" style="width: 100%; text-align:center;"
| |
| − | !Study
| |
| − | ![[Levels_of_Evidence#Evidence|Evidence]]
| |
| − | !Comparator
| |
| − | ![[Levels_of_Evidence#Efficacy|Efficacy]]
| |
| − | |-
| |
| − | |[http://ascopubs.org/doi/full/10.1200/JCO.2012.46.4743 Schaich et al. 2013 (AML2003)]
| |
| − | | style="background-color:#91cf61" |Non-randomized portion of RCT
| |
| − | | style="background-color:#d3d3d3" |
| |
| − | | style="background-color:#d3d3d3" |
| |
| − | |-
| |
| − | |[http://ascopubs.org/doi/full/10.1200/JCO.2012.46.4990 Serve et al. 2013]
| |
| − | | style="background-color:#1a9851" |Randomized Phase II (C)
| |
| − | |7+3d & Sorafenib
| |
| − | | style="background-color:#ffffbf" |Seems not superior
| |
| − | |-
| |
| − | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4504945/ Dombret et al. 2015 (AZA-AML-001)]
| |
| − | | style="background-color:#1a9851" |Phase III (C)
| |
| − | |[[#Azacitidine_monotherapy|Azacitidine]]
| |
| − | | style="background-color:#fee08b" |Might have inferior OS
| |
| − | |-
| |
| − | |[https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(15)00362-9/fulltext Röllig et al. 2015 (SORAML)]
| |
| − | | style="background-color:#1a9851" |Randomized Phase II (C)
| |
| − | |7+3d & Sorafenib
| |
| − | | style="background-color:#fc8d59" |Seems to have inferior EFS
| |
| − | |-
| |
| − | |[http://ascopubs.org/doi/abs/10.1200/JCO.2016.34.15_suppl.7000 Lancet et al. 2016 (CLTR0310-301)]
| |
| − | | style="background-color:#1a9851" |Phase III (C)
| |
| − | |[[#CPX-351_monotherapy|CPX-351]]
| |
| − | | style="background-color:#d73027" |Inferior OS
| |
| | |- | | |- |
| | |} | | |} |
| − | ''Note: this was the upper bound of the allowable daunorubicin dose in AZA-AML-001.''
| |
| | ====Chemotherapy==== | | ====Chemotherapy==== |
| | *[[Cytarabine (Cytosar)]] 100 mg/m<sup>2</sup>/day IV continuous infusion on days 1 to 7 (total dose: 700 mg/m<sup>2</sup>) | | *[[Cytarabine (Cytosar)]] 100 mg/m<sup>2</sup>/day IV continuous infusion on days 1 to 7 (total dose: 700 mg/m<sup>2</sup>) |
| − | *[[Daunorubicin (Cerubidine)]] 60 mg/m<sup>2</sup> IV once per day on days 3 to 5
| |
| − | **Note: Dombret et al. 2015 did not specify which days the daunorubicin is administered
| |
| − |
| |
| − | '''7-day course'''
| |
| − | ====Subsequent treatment====
| |
| − | *AML2003: [[#HiDAC|HiDAC]] versus MAC/MAMAC/MAC consolidation
| |
| − | *CLTR0310-301: [[#5.2B2d|5+2d consolidation]]
| |
| − |
| |
| − | ===Variant #2, CI Ara-C (200 mg/m<sup>2</sup>) {{#subobject:cf53dd|Variant=1}}===
| |
| − | {| class="wikitable" style="width: 100%; text-align:center;"
| |
| − | !Study
| |
| − | ![[Levels_of_Evidence#Evidence|Evidence]]
| |
| − | !Comparator
| |
| − | ![[Levels_of_Evidence#Efficacy|Efficacy]]
| |
| − | |-
| |
| − | |[https://www.nature.com/leu/journal/v18/n5/full/2403336a.html Holowiecki et al. 2004 (PALG AML1/1999)]
| |
| − | | style="background-color:#1a9851" |Phase III (C)
| |
| − | |[[#DAC|DAC]]
| |
| − | | style="background-color:#d73027" |Inferior CR rate after first induction
| |
| − | |-
| |
| − | | rowspan="2" |[http://jco.ascopubs.org/content/30/20/2441.full Holowiecki et al. 2012 (PALG AML1/2004)]
| |
| − | | rowspan="2" style="background-color:#1a9851" |Phase III (C)
| |
| − | |[[#DAC|DAC]]
| |
| − | | style="background-color:#d73027" |Inferior OS
| |
| − | |-
| |
| − | |DAF
| |
| − | | style="background-color:#fc8d59" |Seems to have inferior OS
| |
| − | |-
| |
| − | |[https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(12)60485-1/fulltext Castaigne et al. 2012 (ALFA-0701)]
| |
| − | | style="background-color:#1a9851" |Phase III (C)
| |
| − | |[[#7.2B3d_.26_GO|7+3d & GO]]
| |
| − | | style="background-color:#fc8d59" |Seems to have inferior OS
| |
| − | |-
| |
| − | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5754190/ Stone et al. 2017 (RATIFY)]
| |
| − | | style="background-color:#1a9851" |Phase III (C)
| |
| − | |[[Acute_myeloid_leukemia,_FLT3-positive#Cytarabine.2C_Daunorubicin.2C_Midostaurin|7+3d & Midostaurin]]
| |
| − | | style="background-color:#d73027" |Inferior OS
| |
| − | |-
| |
| − | |}
| |
| − | ''Note: patients in RATIFY had FLT3+ disease.''
| |
| − | ====Chemotherapy====
| |
| − | *[[Cytarabine (Cytosar)]] 200 mg/m<sup>2</sup>/day IV continuous infusion on days 1 to 7 (total dose: 1400 mg/m<sup>2</sup>)
| |
| − | *[[Daunorubicin (Cerubidine)]] 60 mg/m<sup>2</sup> IV over 5 minutes once per day on days 1 to 3
| |
| − |
| |
| − | ====Supportive medications====
| |
| − | *"According to commonly accepted guidelines with no prophylactic IV antibiotics"
| |
| − | *[[:Category:Granulocyte_colony-stimulating_factors|Granulocyte colony-stimulating factor]] recommended only for patients older than 50 years old whose leukemic blasts were negative for CD114 expression
| |
| − |
| |
| − | '''7-day course'''
| |
| − | ====Subsequent treatment====
| |
| − | *Patients with only partial remission in both PALG studies underwent a second course with the same drugs, doses, and schedule.
| |
| − | *PALG AML1/1999, non-responders: [[#CLAG|CLAG salvage]].
| |
| − | *Patients in remission in both PALG studies: [[#HAM|HAM]], then [[#HiDAC|HiDAC]] consolidation
| |
| − | *ALFA-0701, CR or CRp: [[#Cytarabine_.26_Daunorubicin|Cytarabine & daunorubicin consolidation]]
| |
| − |
| |
| − | ===References===
| |
| − | # '''PALG AML1/1999:''' Holowiecki J, Grosicki S, Robak T, Kyrcz-Krzemien S, Giebel S, Hellmann A, Skotnicki A, Jedrzejczak WW, Konopka L, Kuliczkowski K, Zdziarska B, Dmoszyńska A, Marianska B, Pluta A, Zawilska K, Komarnicki M, Kloczko J, Sulek K, Haus O, Stella-Holowiecka B, Baran W, Jakubas B, Paluszewska M, Wierzbowska A, Kielbinski M, Jagoda K; Polish Adult Leukemia Group (PALG). Addition of cladribine to daunorubicin and cytarabine increases complete remission rate after a single course of induction treatment in acute myeloid leukemia: multicenter, phase III study. Leukemia. 2004 May;18(5):989-97. [https://www.nature.com/leu/journal/v18/n5/full/2403336a.html link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/14999298 PubMed]
| |
| − | # '''PALG AML1/2004:''' Holowiecki J, Grosicki S, Giebel S, Robak T, Kyrcz-Krzemien S, Kuliczkowski K, Skotnicki AB, Hellmann A, Sulek K, Dmoszyńska 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. J Clin Oncol. 2012 Jul 10;30(20):2441-8. Epub 2012 Apr 16. [http://jco.ascopubs.org/content/30/20/2441.full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/22508825 PubMed]
| |
| − | # '''ALFA-0701:''' Castaigne S, Pautas C, Terré C, Raffoux E, Bordessoule D, Bastie JN, Legrand O, Thomas X, Turlure P, Reman O, de Revel T, Gastaud L, de Gunzburg N, Contentin N, Henry E, Marolleau JP, Aljijakli A, Rousselot P, Fenaux P, Preudhomme C, Chevret S, Dombret H; Acute Leukemia French Association. Effect of gemtuzumab ozogamicin on survival of adult patients with de-novo acute myeloid leukaemia (ALFA-0701): a randomised, open-label, phase 3 study. Lancet. 2012 Apr 21;379(9825):1508-16. Epub 2012 Apr 5. [https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(12)60485-1/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/22482940 PubMed]
| |
| − | # '''AML2003:''' Schaich M, Parmentier S, Kramer M, Illmer T, Stölzel F, Röllig C, Thiede C, Hänel M, Schäfer-Eckart K, Aulitzky W, Einsele H, Ho AD, Serve H, Berdel WE, Mayer J, Schmitz N, Krause SW, Neubauer A, Baldus CD, Schetelig J, Bornhäuser M, Ehninger G. High-dose cytarabine consolidation with or without additional amsacrine and mitoxantrone in acute myeloid leukemia: results of the prospective randomized AML2003 trial. J Clin Oncol. 2013 Jun 10;31(17):2094-102. Epub 2013 Apr 29. [http://ascopubs.org/doi/full/10.1200/JCO.2012.46.4743 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/23630210 PubMed]
| |
| − | # Serve H, Krug U, Wagner R, Sauerland MC, Heinecke A, Brunnberg U, Schaich M, Ottmann O, Duyster J, Wandt H, Fischer T, Giagounidis A, Neubauer A, Reichle A, Aulitzky W, Noppeney R, Blau I, Kunzmann V, Stuhlmann R, Krämer A, Kreuzer KA, Brandts C, Steffen B, Thiede C, Müller-Tidow C, Ehninger G, Berdel WE. Sorafenib in combination with intensive chemotherapy in elderly patients with acute myeloid leukemia: results from a randomized, placebo-controlled trial. J Clin Oncol. 2013 Sep 1;31(25):3110-8. Epub 2013 Jul 29. [http://ascopubs.org/doi/full/10.1200/JCO.2012.46.4990 link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/23897964 PubMed]
| |
| − | # '''AZA-AML-001:''' Dombret H, Seymour JF, Butrym A, Wierzbowska A, Selleslag D, Jang JH, Kumar R, Cavenagh J, Schuh AC, Candoni A, Récher C, Sandhu I, Bernal Del Castillo T, Al-Ali HK, Martinelli G, Falantes J, Noppeney R, Stone RM, Minden MD, McIntyre H, Songer S, Lucy LM, Beach CL, Döhner H. International phase 3 study of azacitidine vs conventional care regimens in older patients with newly diagnosed AML with >30% blasts. Blood. 2015 Jul 16;126(3):291-9. Epub 2015 May 18. [http://www.bloodjournal.org/content/126/3/291.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4504945/ link to PMC article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/25987659 PubMed]
| |
| − | ## '''Subgroup analysis:''' Seymour JF, Döhner H, Butrym A, Wierzbowska A, Selleslag D, Jang JH, Kumar R, Cavenagh J, Schuh AC, Candoni A, Récher C, Sandhu I, Del Castillo TB, Al-Ali HK, Falantes J, Stone RM, Minden MD, Weaver J, Songer S, Beach CL, Dombret H. Azacitidine improves clinical outcomes in older patients with acute myeloid leukaemia with myelodysplasia-related changes compared with conventional care regimens. BMC Cancer. 2017 Dec 14;17(1):852. [https://bmccancer.biomedcentral.com/articles/10.1186/s12885-017-3803-6 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5731212/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/29241450 PubMed]
| |
| − | # '''SORAML:''' Röllig C, Serve H, Hüttmann A, Noppeney R, Müller-Tidow C, Krug U, Baldus CD, Brandts CH, Kunzmann V, Einsele H, Krämer A, Schäfer-Eckart K, Neubauer A, Burchert A, Giagounidis A, Krause SW, Mackensen A, Aulitzky W, Herbst R, Hänel M, Kiani A, Frickhofen N, Kullmer J, Kaiser U, Link H, Geer T, Reichle A, Junghanß C, Repp R, Heits F, Dürk H, Hase J, Klut IM, Illmer T, Bornhäuser M, Schaich M, Parmentier S, Görner M, Thiede C, von Bonin M, Schetelig J, Kramer M, Berdel WE, Ehninger G; Study Alliance Leukaemia. Addition of sorafenib versus placebo to standard therapy in patients aged 60 years or younger with newly diagnosed acute myeloid leukaemia (SORAML): a multicentre, phase 2, randomised controlled trial. Lancet Oncol. 2015 Dec;16(16):1691-9. Epub 2015 Nov 6. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(15)00362-9/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/26549589 PubMed]
| |
| − | # '''Abstract:''' Lancet JE, Uy GL, Cortes JE, Newell LF, Lin TL, Ritchie EK, Stuart RK, Strickland SA, Hogge D, Solomon SR, Stone RM, Bixby DL, Kolitz JE, Schiller GJ, Wieduwilt MJ, Ryan DH, Hoering A, Chiarella M, Louie AC, Medeiros BC. Final results of a phase III randomized trial of CPX-351 versus 7+3 in older patients with newly diagnosed high risk (secondary) AML. J Clin Oncol. 2016 34:15_suppl, 7000-7000 [http://ascopubs.org/doi/abs/10.1200/JCO.2016.34.15_suppl.7000 link to abstract] '''contains partial protocol''' [https://clinicaltrials.gov/ct2/show/NCT01696084 ClinicalTrials.gov]
| |
| − | <!-- # '''Abstract:''' R. M. Stone, H. Dohner, G. Ehninger, M. Villeneuve, T. Teasdale, J. D. Virkus, L. R. Bressler, M. M. Seiler, G. Marcucci, R. A. Larson. CALGB 10603 (RATIFY): A randomized phase III study of induction (daunorubicin/cytarabine) and consolidation (high-dose cytarabine) chemotherapy combined with midostaurin or placebo in treatment-naive patients with FLT3 mutated AML. 2011 ASCO Annual Meeting abstract TPS199. [http://meetinglibrary.asco.org/content/81555-102 link to abstract]
| |
| − | # '''Abstract:''' Richard M. Stone, Sumithra Mandrekar, Ben L Sanford, Susan Geyer, Clara D. Bloomfield, Konstanze Dohner, Christian Thiede, Guido Marcucci, Francesco Lo-Coco, Rebecca B. Klisovic, Andrew Wei, Jorge Sierra, Miguel A. Sanz, Joseph M. Brandwein, Theo de Witte, Dietger Niederwieser, Frederick R. Appelbaum, Bruno C. Medeiros, Martin S Tallman, Jurgen Krauter, Richard F. Schlenk, Arnold Ganser, Hubert Serve, Gerhard Ehninger, Sergio Amadori, Richard A. Larson, Hartmut Dohner. The Multi-Kinase Inhibitor Midostaurin (M) Prolongs Survival Compared with Placebo (P) in Combination with Daunorubicin (D)/Cytarabine (C) Induction (ind), High-Dose C Consolidation (consol), and As Maintenance (maint) Therapy in Newly Diagnosed Acute Myeloid Leukemia (AML) Patients (pts) Age 18-60 with FLT3 Mutations (muts): An International Prospective Randomized (rand) P-Controlled Double-Blind Trial (CALGB 10603/RATIFY [Alliance]). 2015 ASH Annual Meeting plenary abstract 6. [https://ash.confex.com/ash/2015/webprogramscheduler/Paper80269.html link to abstract] '''contains protocol''' [https://clinicaltrials.gov/ct2/show/NCT00651261 Daunorubicin, Cytarabine, and Midostaurin in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia (NCT00651261) at ClinicalTrials.gov] -->
| |
| − | # '''RATIFY:''' Stone RM, Mandrekar SJ, Sanford BL, Laumann K, Geyer S, Bloomfield CD, Thiede C, Prior TW, Döhner K, Marcucci G, Lo-Coco F, Klisovic RB, Wei A, Sierra J, Sanz MA, Brandwein JM, de Witte T, Niederwieser D, Appelbaum FR, Medeiros BC, Tallman MS, Krauter J, Schlenk RF, Ganser A, Serve H, Ehninger G, Amadori S, Larson RA, Döhner H. Midostaurin plus chemotherapy for acute myeloid leukemia with a FLT3 mutation. N Engl J Med. 2017 Aug 3;377(5):454-464. Epub 2017 Jun 23. [https://www.nejm.org/doi/full/10.1056/NEJMoa1614359 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5754190/ link to PMC article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/28644114 PubMed]
| |
| − |
| |
| − | ==7+3d (high-dose) {{#subobject:9e2666|Regimen=1}}==
| |
| − | {| class="wikitable" style="float:right; margin-left: 5px;"
| |
| − | |-
| |
| − | |[[#top|back to top]]
| |
| − | |}
| |
| − | 7+3d: '''<u>7</u>''' days of cytarabine + '''<u>3</u>''' days of '''<u>d</u>'''aunorubicin
| |
| − | ===Variant #1, CI Ara-C (100 mg/m<sup>2</sup>) {{#subobject:70583e|Variant=1}}===
| |
| − | {| class="wikitable" style="width: 100%; text-align:center;"
| |
| − | !Study
| |
| − | ![[Levels_of_Evidence#Evidence|Evidence]]
| |
| − | !Comparator
| |
| − | ![[Levels_of_Evidence#Efficacy|Efficacy]]
| |
| − | |-
| |
| − | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4480917/ Fernandez et al. 2009 (ECOG E1900)]
| |
| − | | style="background-color:#1a9851" |Phase III (E)
| |
| − | |[[#7.2B3d_.28standard-dose.29|7+3d (standard-dose)]]
| |
| − | | style="background-color:#1a9850" |Superior OS
| |
| − | |-
| |
| − | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4800702/ Zeidner et al. 2015 (JHOC-J1101)]
| |
| − | | style="background-color:#1a9851" |Randomized Phase II (C)
| |
| − | |FLAM
| |
| − | | style="background-color:#d73027" |Inferior CR rate
| |
| − | |-
| |
| − | |}
| |
| − | ====Chemotherapy====
| |
| − | *[[Cytarabine (Cytosar)]] 100 mg/m<sup>2</sup>/day IV continuous infusion on days 1 to 7 (total dose: 700 mg/m<sup>2</sup>)
| |
| − | *[[Daunorubicin (Cerubidine)]] 90 mg/m<sup>2</sup> IV once per day on days 1 to 3
| |
| − |
| |
| − | '''7-day course'''
| |
| − | ====Subsequent treatment====
| |
| − | *JHOC-J1101: Patients with residual leukemia at day 14 underwent [[#5.2B2d_2|5+2d salvage]]
| |
| − |
| |
| − | ===Variant #2, CI Ara-C (200 mg/m<sup>2</sup>) {{#subobject:664ec|Variant=1}}===
| |
| − | {| class="wikitable" style="width: 100%; text-align:center;"
| |
| − | !Study
| |
| − | ![[Levels_of_Evidence#Evidence|Evidence]]
| |
| − | !Comparator
| |
| − | ![[Levels_of_Evidence#Efficacy|Efficacy]]
| |
| − | |-
| |
| − | |[http://www.nejm.org/doi/full/10.1056/NEJMoa0901409 Löwenberg et al. 2009 (HOVON 43 AML/SAKK 30/01)]
| |
| − | | style="background-color:#1a9851" |Phase III (E)
| |
| − | |[[#7.2B3d_.28standard-dose.29|7+3d (standard-dose)]]
| |
| − | | style="background-color:#1a9850" |Superior CR rate
| |
| − | |-
| |
| − | |[http://ascopubs.org/doi/full/10.1200/JCO.2017.72.8618 Lee et al. 2017 (COSAH C-022)]
| |
| − | | style="background-color:#1a9851" |Phase III (C)
| |
| − | |[[#7.2B3i|7+3i]]
| |
| − | | style="background-color:#ffffbf" |Seems not superior
| |
| − | |-
| |
| − | |}
| |
| − | ====Chemotherapy====
| |
| − | *[[Cytarabine (Cytosar)]] 200 mg/m<sup>2</sup>/day IV continuous infusion on days 1 to 7 (total dose: 1400 mg/m<sup>2</sup>)
| |
| − | *[[Daunorubicin (Cerubidine)]] 90 mg/m<sup>2</sup> IV once per day on days 1 to 3
| |
| − |
| |
| − | '''7-day course'''
| |
| − | ====Subsequent treatment====
| |
| − | *HOVON 43 AML/SAKK 30/01: [[#IDAC|MiDAC consolidation]]
| |
| − | *COSAH C-022, with CR: [[#HiDAC|HiDAC consolidation]] if good- or intermediate-risk cytogenetics, or cytarabine & etoposide consolidation if high-risk cytogenetics.
| |
| − |
| |
| − | ===References===
| |
| − | # '''HOVON 43 AML/SAKK 30/01:''' 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. 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. [http://www.nejm.org/doi/full/10.1056/NEJMoa0901409 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/19776405 PubMed]
| |
| − | # '''ECOG E1900:''' 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. [http://www.nejm.org/doi/full/10.1056/NEJMoa0904544 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4480917/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/19776406 PubMed]
| |
| − | ## '''Update:''' Luskin MR, Lee JW, Fernandez HF, Abdel-Wahab O, Bennett JM, Ketterling RP, Lazarus HM, Levine RL, Litzow MR, Paietta EM, Patel JP, Racevskis J, Rowe JM, Tallman MS, Sun Z, Luger SM. Benefit of high-dose daunorubicin in AML induction extends across cytogenetic and molecular groups. Blood. 2016 Mar 24;127(12):1551-8. Epub 2016 Jan 11. [http://www.bloodjournal.org/content/127/12/1551.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4807422/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/26755712 PubMed]
| |
| − | # '''JHOC-J1101:''' Zeidner JF, Foster MC, Blackford AL, Litzow MR, Morris LE, Strickland SA, Lancet JE, Bose P, Levy MY, Tibes R, Gojo I, Gocke CD, Rosner GL, Little RF, Wright JJ, Doyle LA, Smith BD, Karp JE. Randomized multicenter phase II study of flavopiridol (alvocidib), cytarabine, and mitoxantrone (FLAM) versus cytarabine/daunorubicin (7+3) in newly diagnosed acute myeloid leukemia. Haematologica. 2015 Sep;100(9):1172-9. Epub 2015 May 28. [http://www.haematologica.org/content/100/9/1172 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4800702/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/26022709 PubMed]
| |
| − | # '''COSAH C-022:''' Lee JH, Kim H, Joo YD, Lee WS, Bae SH, Zang DY, Kwon J, Kim MK, Lee J, Lee GW, Lee JH, Choi Y, Kim DY, Hur EH, Lim SN, Lee SM, Ryoo HM, Kim HJ, Hyun MS, Lee KH; Cooperative Study Group A for Hematology. Prospective randomized comparison of idarubicin and high-dose daunorubicin in induction chemotherapy for newly diagnosed acute myeloid leukemia. J Clin Oncol. 2017 Aug 20;35(24):2754-2763. Epub 2017 Jun 20. [http://ascopubs.org/doi/full/10.1200/JCO.2017.72.8618 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/28632487 PubMed]
| |
| − |
| |
| − | ==7+3d & GO {{#subobject:869f84|Regimen=1}}==
| |
| − | {| class="wikitable" style="float:right; margin-left: 5px;"
| |
| − | |-
| |
| − | |[[#top|back to top]]
| |
| − | |}
| |
| − | 7+3d & GO: '''<u>7</u>''' days of Cytarabine, '''<u>3</u>''' days of '''<u>d</u>'''aunorubicin, '''<u>G</u>'''emtuzumab '''<u>O</u>'''zogamicin
| |
| − | ===Regimen {{#subobject:4c0a05|Variant=1}}===
| |
| − | {| class="wikitable" style="width: 100%; text-align:center;"
| |
| − | !Study
| |
| − | ![[Levels_of_Evidence#Evidence|Evidence]]
| |
| − | !Comparator
| |
| − | ![[Levels_of_Evidence#Efficacy|Efficacy]]
| |
| − | |-
| |
| − | |[https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(12)60485-1/fulltext Castaigne et al. 2012 (ALFA-0701)]
| |
| − | | style="background-color:#1a9851" |Phase III (E)
| |
| − | |[[#7.2B3d_.28intermediate-dose.29|7+3d (intermediate-dose)]]
| |
| − | | style="background-color:#91cf60" |Seems to have superior OS
| |
| − | |-
| |
| − | |}
| |
| − | ====Chemotherapy====
| |
| − | *[[Cytarabine (Cytosar)]] 200 mg/m<sup>2</sup>/day IV continuous infusion on days 1 to 7 (total dose: 1400 mg/m<sup>2</sup>)
| |
| | *[[Daunorubicin (Cerubidine)]] 60 mg/m<sup>2</sup> IV once per day on days 1 to 3 | | *[[Daunorubicin (Cerubidine)]] 60 mg/m<sup>2</sup> IV once per day on days 1 to 3 |
| − | *[[Gemtuzumab ozogamicin (Mylotarg)]] 3 mg/m<sup>2</sup> (maximum dose of 5 mg) IV over 2 hours once per day on days 1, 4, 7
| |
| − |
| |
| − | '''7-day course'''
| |
| − | ====Subsequent treatment====
| |
| − | *Patients in CR or CRp and platelet count at least 100 x 10<sup>9</sup> by day 45 after the initiation of chemotherapy: [[#Cytarabine.2C_Daunorubicin.2C_Gemtuzumab_ozogamicin|Cytarabine, Daunorubicin, Gemtuzumab ozogamicin consolidation]]
| |
| − | *Patients in CR or CRp and platelet count less than 100 x 10<sup>9</sup> by day 45 after the initiation of chemotherapy: [[#Cytarabine_.26_Daunorubicin|Cytarabine & Daunorubicin consolidation]]
| |
| − |
| |
| − | ===References===
| |
| − | # '''ALFA-0701:''' Castaigne S, Pautas C, Terré C, Raffoux E, Bordessoule D, Bastie JN, Legrand O, Thomas X, Turlure P, Reman O, de Revel T, Gastaud L, de Gunzburg N, Contentin N, Henry E, Marolleau JP, Aljijakli A, Rousselot P, Fenaux P, Preudhomme C, Chevret S, Dombret H; Acute Leukemia French Association. Effect of gemtuzumab ozogamicin on survival of adult patients with de-novo acute myeloid leukaemia (ALFA-0701): a randomised, open-label, phase 3 study. Lancet. 2012 Apr 21;379(9825):1508-16. [https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(12)60485-1/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/22482940 PubMed]
| |
| − |
| |
| − | ==7+3i {{#subobject:717935|Regimen=1}}==
| |
| − | {| class="wikitable" style="float:right; margin-left: 5px;"
| |
| − | |-
| |
| − | |[[#top|back to top]]
| |
| − | |}
| |
| − | 7+3i: '''<u>7</u>''' days of cytarabine + '''<u>3</u>''' days of '''<u>i</u>'''darubicin
| |
| − | <br>AI: '''<u>A</u>'''ra-C (Cytarabine) & '''<u>I</u>'''darubicin
| |
| − | <br>IA: '''<u>I</u>'''darubicin & '''<u>A</u>'''ra-C (Cytarabine)
| |
| − | ===Variant #1, 80/12, intermittent Ara-C {{#subobject:bdc11c|Variant=1}}===
| |
| − | {| class="wikitable" style="width: 100%; text-align:center;"
| |
| − | !Study
| |
| − | ![[Levels_of_Evidence#Evidence|Evidence]]
| |
| − | !Comparator
| |
| − | ![[Levels_of_Evidence#Efficacy|Efficacy]]
| |
| − | |-
| |
| − | |[https://www.ncbi.nlm.nih.gov/pubmed/8916311 Masaoka et al. 1996]
| |
| − | | style="background-color:#1a9851" |Randomized Phase II (E)
| |
| − | |[[#7.2B3d_.28standard-dose.29|7+3d (standard-dose)]]
| |
| − | | style="background-color:#91cf60" |Seems to have superior CR rate
| |
| − | |-
| |
| − | |}
| |
| − | ====Chemotherapy====
| |
| − | *[[Cytarabine (Cytosar)]] 80 mg/m<sup>2</sup> IV over 2 hours q12h on days 1 to 7
| |
| − | *[[Idarubicin (Idamycin)]] 12 mg/m<sup>2</sup> IV bolus once per day on days 1 to 3
| |
| − |
| |
| − | '''7-day course'''
| |
| − |
| |
| − | ===Variant #2, 100/12, CI Ara-C {{#subobject:c6cda|Variant=1}}===
| |
| − | {| class="wikitable" style="width: 100%; text-align:center;"
| |
| − | !Study
| |
| − | ![[Levels_of_Evidence#Evidence|Evidence]]
| |
| − | !Comparator
| |
| − | ![[Levels_of_Evidence#Efficacy|Efficacy]]
| |
| − | |-
| |
| − | |[https://www.ncbi.nlm.nih.gov/pubmed/8290968 Haas et al. 1993]
| |
| − | | style="background-color:#91cf61" |Non-randomized
| |
| − | | style="background-color:#d3d3d3" |
| |
| − | | style="background-color:#d3d3d3" |
| |
| − | |-
| |
| − | |[http://www.bloodjournal.org/content/103/2/479.long Rowe et al. 2004]
| |
| − | | style="background-color:#1a9851" |Phase III (E)
| |
| − | |[[#7.2B3d_.28standard-dose.29|7+3d (standard-dose)]]<br> 7+3d + GM-CSF<br> 7+3i + GM-CSF<br> [[#7.2B3m|7+3m]]<br> 7+3m + GM-CSF
| |
| − | | style="background-color:#ffffbf" |Seems not superior
| |
| − | |-
| |
| − | |}
| |
| − | ====Chemotherapy====
| |
| − | *[[Cytarabine (Cytosar)]] 100 mg/m<sup>2</sup>/day IV continuous infusion on days 1 to 7 (total dose: 700 mg/m<sup>2</sup>)
| |
| − | *[[Idarubicin (Idamycin)]] 12 mg/m<sup>2</sup> IV once per day on days 1 to 3
| |
| − |
| |
| − | '''7-day course'''
| |
| − |
| |
| − | ''Patients in Rowe et al. 2004 with persistent disease at day 14 (greater than 5% blasts) underwent an identical second cycle of 7+3i.''
| |
| − |
| |
| − | ===Variant #3, 100/13, CI Ara-C {{#subobject:7f2eec|Variant=1}}===
| |
| − | {| class="wikitable" style="width: 100%; text-align:center;"
| |
| − | !Study
| |
| − | ![[Levels_of_Evidence#Evidence|Evidence]]
| |
| − | !Comparator
| |
| − | ![[Levels_of_Evidence#Efficacy|Efficacy]]
| |
| − | |-
| |
| − | |[http://www.bloodjournal.org/content/79/2/313 Wiernik et al. 1992]
| |
| − | | style="background-color:#1a9851" |Phase III (E)
| |
| − | |[[#7.2B3d_.28standard-dose.29|7+3d (standard-dose)]]
| |
| − | | style="background-color:#91cf60" |Seems to have superior OS
| |
| − | |-
| |
| − | |}
| |
| − | ====Chemotherapy====
| |
| − | *[[Cytarabine (Cytosar)]] 100 mg/m<sup>2</sup>/day IV continuous infusion on days 1 to 7 (total dose: 700 mg/m<sup>2</sup>)
| |
| − | *[[Idarubicin (Idamycin)]] 13 mg/m<sup>2</sup> IV once per day on days 1 to 3
| |
| − |
| |
| − | '''7-day course'''
| |
| − |
| |
| − | ===Variant #4, 200/12, CI Ara-C {{#subobject:f33de6|Variant=1}}===
| |
| − | {| class="wikitable" style="width: 100%; text-align:center;"
| |
| − | !Study
| |
| − | ![[Levels_of_Evidence#Evidence|Evidence]]
| |
| − | !Comparator
| |
| − | ![[Levels_of_Evidence#Efficacy|Efficacy]]
| |
| − | |-
| |
| − | |[http://www.nejm.org/doi/full/10.1056/NEJMoa025406 Löwenberg et al. 2003 (HOVON/SAKK AML 29)]
| |
| − | | style="background-color:#1a9851" |Phase III (C)
| |
| − | |7+3i & G-CSF
| |
| − | | style="background-color:#fc8d59" |Seems to have inferior DFS
| |
| − | |-
| |
| − | |[http://ascopubs.org/doi/full/10.1200/JCO.2009.23.2652 Pautas et al. 2010 (ALFA-9801)]
| |
| − | | style="background-color:#1a9851" |Phase III (C)
| |
| − | |[[#7.2B3d_.28high-dose.29|7+3d (high-dose)]]<br> 7+4i
| |
| − | | style="background-color:#ffffbf" |Seems not superior
| |
| − | |-
| |
| − | |[http://www.nejm.org/doi/full/10.1056/NEJMoa1010222 Löwenberg et al. 2011 (HOVON/SAKK AML 42)]
| |
| − | | style="background-color:#1a9851" |Phase III (C)
| |
| − | |HDAC+3i
| |
| − | | style="background-color:#ffffbf" |Seems not superior
| |
| − | |-
| |
| − | |[http://www.bloodjournal.org/content/129/12/1636.long Löwenberg et al. 2017 (HOVON-102)]
| |
| − | | style="background-color:#1a9851" |Phase III (C)
| |
| − | |7+3i & Clofarabine
| |
| − | | style="background-color:#ffffbf" |Seems not superior
| |
| − | |-
| |
| − | |[http://ascopubs.org/doi/full/10.1200/JCO.2017.72.8618 Lee et al. 2017 (COSAH C-022)]
| |
| − | | style="background-color:#1a9851" |Phase III (C)
| |
| − | |[[#7.2B3d_.28high-dose.29|7+3d (high-dose)]]
| |
| − | | style="background-color:#ffffbf" |Seems not superior
| |
| − | |-
| |
| − | |}
| |
| − | ====Chemotherapy====
| |
| − | *[[Cytarabine (Cytosar)]] 200 mg/m<sup>2</sup>/day IV continuous infusion on days 1 to 7 (total dose: 1400 mg/m<sup>2</sup>)
| |
| − | *[[Idarubicin (Idamycin)]] 12 mg/m<sup>2</sup> IV over 3 hours once per day on days 1 to 3
| |
| − | **Note: in HOVON/SAKK AML 29 & AML 42, idarubicin was given on days 5 to 7
| |
| − |
| |
| − | '''7-day course'''
| |
| − | ====Subsequent treatment====
| |
| − | *HOVON/SAKK AML 29 & AML 42: Amsacrine & Cytarabine
| |
| − | *ALFA-9801, patients achieiving CR: [[#Cytarabine_.26_Idarubicin_2|cytarabine & idarubicin consolidation]]
| |
| − | *COSAH C-022, patients achieving CR, good- or intermediate-risk cytogenetics: [[#HiDAC|HiDAC consolidation]]
| |
| − | *COSAH C-022, patients achieving CR, high-risk cytogenetics: [[#CYVE|CYVE consolidation]]
| |
| − |
| |
| − | ===Variant #5, with range {{#subobject:eb0168|Variant=1}}===
| |
| − | {| class="wikitable" style="width: 100%; text-align:center;"
| |
| − | !Study
| |
| − | ![[Levels_of_Evidence#Evidence|Evidence]]
| |
| − | !Comparator
| |
| − | ![[Levels_of_Evidence#Efficacy|Efficacy]]
| |
| − | |-
| |
| − | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4504945/ Dombret et al. 2015 (AZA-AML-001)]
| |
| − | | style="background-color:#1a9851" |Phase III (C)
| |
| − | |[[#Azacitidine_monotherapy|Azacitidine]]
| |
| − | | style="background-color:#fee08b" |Might have inferior OS
| |
| − | |-
| |
| − | |}
| |
| − | ====Chemotherapy====
| |
| − | *[[Cytarabine (Cytosar)]] 100 to 200 mg/m<sup>2</sup>/day IV continuous infusion on days 1 to 7 (total dose: 700 to 1400 mg/m<sup>2</sup>)
| |
| − | *[[Idarubicin (Idamycin)]] 9 to 12 mg/m<sup>2</sup> IV once per day 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. [http://www.bloodjournal.org/content/79/2/313 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/1730080 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. [https://www.ncbi.nlm.nih.gov/pubmed/8290968 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. '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/8916311 PubMed]
| |
| − | # '''HOVON/SAKK AML 29:''' Löwenberg B, van Putten W, Theobald M, Gmür J, Verdonck L, Sonneveld P, Fey M, Schouten H, de Greef G, Ferrant A, Kovacsovics T, Gratwohl A, Daenen S, Huijgens P, Boogaerts M; Dutch-Belgian Hemato-Oncology Cooperative Group; Swiss Group for Clinical Cancer Research. Effect of priming with granulocyte colony-stimulating factor on the outcome of chemotherapy for acute myeloid leukemia. N Engl J Med. 2003 Aug 21;349(8):743-52. [http://www.nejm.org/doi/full/10.1056/NEJMoa025406 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/12930926 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. [http://www.bloodjournal.org/content/103/2/479.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/14512295 PubMed]
| |
| − | # '''ALFA-9801:''' Pautas C, Merabet F, Thomas X, Raffoux E, Gardin C, Corm S, Bourhis JH, Reman O, Turlure P, Contentin N, de Revel T, Rousselot P, Preudhomme C, Bordessoule D, Fenaux P, Terré C, Michallet M, Dombret H, Chevret S, Castaigne S. Randomized study of intensified anthracycline doses for induction and recombinant interleukin-2 for maintenance in patients with acute myeloid leukemia age 50 to 70 years: results of the ALFA-9801 study. J Clin Oncol. 2010 Feb 10;28(5):808-14. Epub 2010 Jan 4. [http://ascopubs.org/doi/full/10.1200/JCO.2009.23.2652 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/20048183 PubMed]
| |
| − | # '''HOVON/SAKK AML 42:''' Löwenberg B, Pabst T, Vellenga E, van Putten W, Schouten HC, Graux C, Ferrant A, Sonneveld P, Biemond BJ, Gratwohl A, de Greef GE, Verdonck LF, Schaafsma MR, Gregor M, Theobald M, Schanz U, Maertens J, Ossenkoppele GJ; Dutch-Belgian Cooperative Trial Group for Hemato-Oncology (HOVON) and Swiss Group for Clinical Cancer Research (SAKK) Collaborative Group. Cytarabine dose for acute myeloid leukemia. N Engl J Med. 2011 Mar 17;364(11):1027-36. [http://www.nejm.org/doi/full/10.1056/NEJMoa1010222 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/21410371 PubMed]
| |
| − | # '''AZA-AML-001:''' Dombret H, Seymour JF, Butrym A, Wierzbowska A, Selleslag D, Jang JH, Kumar R, Cavenagh J, Schuh AC, Candoni A, Récher C, Sandhu I, Bernal Del Castillo T, Al-Ali HK, Martinelli G, Falantes J, Noppeney R, Stone RM, Minden MD, McIntyre H, Songer S, Lucy LM, Beach CL, Döhner H. International phase 3 study of azacitidine vs conventional care regimens in older patients with newly diagnosed AML with >30% blasts. Blood. 2015 Jul 16;126(3):291-9. Epub 2015 May 18. [http://www.bloodjournal.org/content/126/3/291.long link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4504945/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/25987659 PubMed]
| |
| − | ## '''Subgroup analysis:''' Seymour JF, Döhner H, Butrym A, Wierzbowska A, Selleslag D, Jang JH, Kumar R, Cavenagh J, Schuh AC, Candoni A, Récher C, Sandhu I, Del Castillo TB, Al-Ali HK, Falantes J, Stone RM, Minden MD, Weaver J, Songer S, Beach CL, Dombret H. Azacitidine improves clinical outcomes in older patients with acute myeloid leukaemia with myelodysplasia-related changes compared with conventional care regimens. BMC Cancer. 2017 Dec 14;17(1):852. [https://bmccancer.biomedcentral.com/articles/10.1186/s12885-017-3803-6 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5731212/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/29241450 PubMed]
| |
| − | # Löwenberg B, Pabst T, Maertens J, van Norden Y, Biemond BJ, Schouten HC, Spertini O, Vellenga E, Graux C, Havelange V, de Greef GE, de Weerdt O, Legdeur MJ, Kuball J, Kooy MV, Gjertsen BT, Jongen-Lavrencic M, van de Loosdrecht AA, van Lammeren-Venema D, Hodossy B, Breems DA, Chalandon Y, Passweg J, Valk PJ, Manz MG, Ossenkoppele GJ; Dutch-Belgian Hemato-Oncology Cooperative Group (HOVON) and Swiss Group for Clinical Cancer Research (SAKK). Therapeutic value of clofarabine in younger and middle-aged (18-65 years) adults with newly diagnosed AML. Blood. 2017 Mar 23;129(12):1636-1645. Epub 2017 Jan 3. [http://www.bloodjournal.org/content/129/12/1636.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/28049642 PubMed]
| |
| − | # '''COSAH C-022:''' Lee JH, Kim H, Joo YD, Lee WS, Bae SH, Zang DY, Kwon J, Kim MK, Lee J, Lee GW, Lee JH, Choi Y, Kim DY, Hur EH, Lim SN, Lee SM, Ryoo HM, Kim HJ, Hyun MS, Lee KH; Cooperative Study Group A for Hematology. Prospective randomized comparison of idarubicin and high-dose daunorubicin in induction chemotherapy for newly diagnosed acute myeloid leukemia. J Clin Oncol. 2017 Aug 20;35(24):2754-2763. Epub 2017 Jun 20. [http://ascopubs.org/doi/full/10.1200/JCO.2017.72.8618 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/28632487 PubMed]
| |
| − |
| |
| − | ==7+3i & Sorafenib {{#subobject:ab6409|Regimen=1}}==
| |
| − | {| class="wikitable" style="float:right; margin-left: 5px;"
| |
| − | |-
| |
| − | |[[#top|back to top]]
| |
| − | |}
| |
| − |
| |
| − | ===Regimen {{#subobject:567ab9|Variant=1}}===
| |
| − | {| class="wikitable" style="width: 100%; text-align:center;"
| |
| − | !Study
| |
| − | ![[Levels_of_Evidence#Evidence|Evidence]]
| |
| − | |-
| |
| − | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2930809/ Ravandi et al. 2010]
| |
| − | | style="background-color:#91cf61" |Phase I/II
| |
| − | |-
| |
| − | |}
| |
| − | ''Regimen details are from the phase II part of the published phase I/II trial.''
| |
| − | ====Chemotherapy====
| |
| − | *[[Cytarabine (Cytosar)]] 1500 mg/m<sup>2</sup>/day IV continuous infusion on days 1 to 4 (total dose: 6000 mg/m<sup>2</sup>)
| |
| − | **Patients older than 60 received: 1500 mg/m<sup>2</sup>/day IV continuous infusion on days 1 to 3 (total dose: 4500 mg/m<sup>2</sup>)
| |
| − | *[[Idarubicin (Idamycin)]] 12 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1 to 3
| |
| | *[[Sorafenib (Nexavar)]] 400 mg PO BID on days 1 to 7 | | *[[Sorafenib (Nexavar)]] 400 mg PO BID on days 1 to 7 |
| | | | |
| | '''7-day course''' | | '''7-day course''' |
| | ====Subsequent treatment==== | | ====Subsequent treatment==== |
| − | *[[#Cytarabine.2C_Idarubicin.2C_Sorafenib|Cytarabine, idarubicin, sorafenib consolidation]] | + | *Patients not achieving a hypoplastic marrow on day 14 received re-induction with 5+2 & sorafenib |
| − | | + | *Patients achieving a CR or CRi: [[#IDAC_.26_Sorafenib|IDAC & sorafenib consolidation]] |
| − | ===References===
| |
| − | <!-- no pre-pub disclosed -->
| |
| − | # 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. Epub 2010 Mar 8. [http://jco.ascopubs.org/content/28/11/1856.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2930809/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/20212254 PubMed]
| |
| − | ## '''Update:''' Ravandi F, Arana Yi C, Cortes JE, Levis M, Faderl S, Garcia-Manero G, Jabbour E, Konopleva M, O'Brien S, Estrov Z, Borthakur G, Thomas D, Pierce S, Brandt M, Pratz K, Luthra R, Andreeff M, Kantarjian H. Final report of phase II study of sorafenib, cytarabine and idarubicin for initial therapy in younger patients with acute myeloid leukemia. Leukemia. 2014 Jul;28(7):1543-5. Epub 2014 Feb 3. [https://www.nature.com/leu/journal/v28/n7/full/leu201454a.html link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4091714/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/24487412 PubMed]
| |
| − | | |
| − | ==7+3i & Vorinostat {{#subobject:1c76f3|Regimen=1}}==
| |
| − | {| class="wikitable" style="float:right; margin-left: 5px;"
| |
| − | |-
| |
| − | |[[#top|back to top]]
| |
| − | |}
| |
| − | | |
| − | ===Regimen {{#subobject:7d051b|Variant=1}}===
| |
| − | {| class="wikitable" style="width: 100%; text-align:center;"
| |
| − | !Study
| |
| − | ![[Levels_of_Evidence#Evidence|Evidence]]
| |
| − | |-
| |
| − | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4879705/ Garcia-Manero et al. 2012]
| |
| − | | style="background-color:#91cf61" |Phase II
| |
| − | |-
| |
| − | |}
| |
| − | ====Chemotherapy====
| |
| − | *[[Cytarabine (Cytosar)]] 1500 mg/m<sup>2</sup>/day IV continuous infusion on days 4 to 7 (total dose: 6000 mg/m<sup>2</sup>)
| |
| − | **Patients older than 60 received: 1500 mg/m<sup>2</sup>/day IV continuous infusion on days 4 to 6 (total dose: 4500 mg/m<sup>2</sup>)
| |
| − | *[[Idarubicin (Idamycin)]] 12 mg/m<sup>2</sup> IV once per day on days 4 to 6
| |
| − | *[[Vorinostat (Zolinza)]] 500 mg PO TID on days 1 to 3
| |
| − | | |
| − | ====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 (Cytosar)]] to prevent fever and rash
| |
| − | | |
| − | '''7-day course for 1 to 2 cycles'''
| |
| − | ====Subsequent treatment====
| |
| − | *[[#Cytarabine.2C_Idarubicin.2C_Vorinostat|Cytarabine, idarubicin, vorinostat consolidation]]
| |
| − | | |
| − | ===References===
| |
| − | <!-- no pre-pub disclosed -->
| |
| − | # 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. [http://jco.ascopubs.org/content/30/18/2204.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4879705/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/22585696 PubMed]
| |
| − | | |
| − | ==7+3m {{#subobject:240c72|Regimen=1}}==
| |
| − | {| class="wikitable" style="float:right; margin-left: 5px;"
| |
| − | |-
| |
| − | |[[#top|back to top]]
| |
| − | |}
| |
| − | 7+3m: '''<u>7</u>''' days of cytarabine + '''<u>3</u>''' days of '''<u>m</u>'''itoxantrone
| |
| − | ===Regimen {{#subobject:7d87af|Variant=1}}===
| |
| − | {| class="wikitable" style="width: 100%; text-align:center;"
| |
| − | !Study
| |
| − | ![[Levels_of_Evidence#Evidence|Evidence]]
| |
| − | !Comparator
| |
| − | ![[Levels_of_Evidence#Efficacy|Efficacy]]
| |
| − | |-
| |
| − | |[http://www.bloodjournal.org/content/103/2/479.long Rowe et al. 2004]
| |
| − | | style="background-color:#1a9851" |Phase III (E)
| |
| − | |[[#7.2B3d_.28standard-dose.29|7+3d (standard-dose)]]<br> 7+3d + GM-CSF<br> [[#7.2B3i|7+3i]]<br> 7+3i + GM-CSF<br> 7+3m + GM-CSF
| |
| − | | style="background-color:#ffffbf" |Seems not superior
| |
| − | |-
| |
| − | |}
| |
| − | ====Chemotherapy====
| |
| − | *[[Cytarabine (Cytosar)]] 100 mg/m<sup>2</sup>/day IV continuous infusion on days 1 to 7 (total dose: 700 mg/m<sup>2</sup>)
| |
| − | *[[Mitoxantrone (Novantrone)]] 12 mg/m<sup>2</sup> IV once per day on days 1 to 3
| |
| − | | |
| − | '''7-day course'''
| |
| − | | |
| − | ''Patients with persistent disease at day 14 (greater than 5% blasts) underwent an identical second cycle of 7+3m.''
| |
| − | | |
| − | ===References===
| |
| − | # 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. [http://www.bloodjournal.org/content/103/2/479.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/14512295 PubMed]
| |
| − | | |
| − | ==ADE (standard-dose Ara-C) {{#subobject:e221d7|Regimen=1}}==
| |
| − | {| class="wikitable" style="float:right; margin-left: 5px;"
| |
| − | |-
| |
| − | |[[#top|back to top]]
| |
| − | |}
| |
| − | ADE: '''<u>A</u>'''ra-C (Cytarabine), '''<u>D</u>'''aunorubicin, '''<u>E</u>'''toposide
| |
| − | <br>7-3-7: '''<u>7</u>''' days of Cytarabine, '''<u>3</u>''' days of Daunorubicin, '''<u>7</u>''' days of Etoposide
| |
| − | <br>8-3-5: '''<u>8</u>''' days of Cytarabine, '''<u>3</u>''' days of Daunorubicin, '''<u>5</u>''' days of Etoposide
| |
| − | <br>10-3-5: '''<u>10</u>''' days of Cytarabine, '''<u>3</u>''' days of Daunorubicin, '''<u>5</u>''' days of Etoposide
| |
| − | ===Variant #1, 7-3-7 {{#subobject:386fd2|Variant=1}}===
| |
| − | {| class="wikitable" style="width: 100%; text-align:center;"
| |
| − | !Study
| |
| − | ![[Levels_of_Evidence#Evidence|Evidence]]
| |
| − | !Comparator
| |
| − | ![[Levels_of_Evidence#Efficacy|Efficacy]]
| |
| − | |-
| |
| − | |[http://www.bloodjournal.org/content/87/5/1710.long Bishop et al. 1996]
| |
| − | | style="background-color:#1a9851" |Phase III (C)
| |
| − | |[[#ADE_.28high-dose_Ara-C.29|ADE (high-dose Ara-C)]]
| |
| − | | style="background-color:#d73027" |Inferior DFS
| |
| − | |-
| |
| − | |}
| |
| − | ====Chemotherapy====
| |
| − | *[[Cytarabine (Cytosar)]] 100 mg/m<sup>2</sup>/day IV continuous infusion on days 1 to 7 (total dose: 700 mg/m<sup>2</sup>)
| |
| − | *[[Daunorubicin (Cerubidine)]] 50 mg/m<sup>2</sup> IV once per day on days 1 to 3
| |
| − | *[[Etoposide (Vepesid)]] 75 mg/m<sup>2</sup> IV once per day on days 1 to 7
| |
| − | | |
| − | '''7-day course, can be repeated up to 3 times if CR not achieved'''
| |
| − | ====Subsequent treatment====
| |
| − | *5-2-5 consolidation x 2
| |
| − | | |
| − | ===Variant #2, 8-3-5, intermittent Ara-C {{#subobject:f7e0ca|Variant=1}}===
| |
| − | {| class="wikitable" style="width: 100%; text-align:center;"
| |
| − | !Study
| |
| − | ![[Levels_of_Evidence#Evidence|Evidence]]
| |
| − | |-
| |
| − | |[http://jco.ascopubs.org/content/31/27/3360.long Burnett et al. 2013 (UK MRC AML15)]
| |
| − | | style="background-color:#1a9851" |Phase III (C)
| |
| − | |-
| |
| − | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4162498/ Gamis et al. 2014 (COG AAML0531)]
| |
| − | | style="background-color:#1a9851" |Phase III (C)
| |
| − | |-
| |
| − | |}
| |
| − | ''Both of these trials have complicated treatment schemas; see papers for details.''
| |
| − | ====Preceding treatment====
| |
| − | *[[#ADE_.28standard-dose_Ara-C.29|ADE 10-3-5 induction]]
| |
| − | | |
| − | ====Chemotherapy====
| |
| − | *[[Cytarabine (Cytosar)]] 100 mg/m<sup>2</sup>/day IV q12h on days 1 to 8
| |
| − | *[[Daunorubicin (Cerubidine)]] 50 mg/m<sup>2</sup> IV once per day on days 1, 3, 5
| |
| − | *[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV once per day on days 1 to 5
| |
| − | | |
| − | '''8-day course'''
| |
| − | ====Subsequent treatment====
| |
| − | *Consolidation (see paper for details)
| |
| − | | |
| − | ===Variant #3, 10-3-5, intermittent Ara-C {{#subobject:77fe46|Variant=1}}===
| |
| − | {| class="wikitable" style="width: 100%; text-align:center;"
| |
| − | !Study
| |
| − | ![[Levels_of_Evidence#Evidence|Evidence]]
| |
| − | |-
| |
| − | |-
| |
| − | |[http://ascopubs.org/doi/full/10.1200/JCO.2009.22.9088 Burnett et al. 2010 (UK MRC AML12)]
| |
| − | | style="background-color:#1a9851" |Phase III (C)
| |
| − | |-
| |
| − | |[http://jco.ascopubs.org/content/31/27/3360.long Burnett et al. 2013 (UK MRC AML15)]
| |
| − | | style="background-color:#1a9851" |Phase III (C)
| |
| − | |-
| |
| − | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4162498/ Gamis et al. 2014 (COG AAML0531)]
| |
| − | | style="background-color:#1a9851" |Phase III (C)
| |
| − | |-
| |
| − | |}
| |
| − | ''These trials have complicated treatment schemas; see papers for details.''
| |
| − | ====Chemotherapy====
| |
| − | *[[Cytarabine (Cytosar)]] 100 mg/m<sup>2</sup>/day IV q12h on days 1 to 10
| |
| − | *[[Daunorubicin (Cerubidine)]] 50 mg/m<sup>2</sup> IV once per day on days 1, 3, 5
| |
| − | *[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV once per day on days 1 to 5
| |
| − | | |
| − | '''10-day course'''
| |
| − | ====Subsequent treatment====
| |
| − | *ADE 8-3-5, then consolidation
| |
| − | | |
| − | ===Variant #4, 10-3-5, CI Ara-C {{#subobject:7ce6f9|Variant=1}}===
| |
| − | {| class="wikitable" style="width: 100%; text-align:center;"
| |
| − | !Study
| |
| − | ![[Levels_of_Evidence#Evidence|Evidence]]
| |
| − | !Comparator
| |
| − | ![[Levels_of_Evidence#Efficacy|Efficacy]]
| |
| − | |-
| |
| − | |[http://jco.ascopubs.org/content/32/3/219.full Willemze et al. 2013 (AML-12)]
| |
| − | | style="background-color:#1a9851" |Phase III (C)
| |
| − | |[[#ADE_.28high-dose_Ara-C.29|ADE (high-dose Ara-C)]]
| |
| − | | style="background-color:#fee08b" |Might have inferior OS
| |
| − | |-
| |
| − | |}
| |
| − | ====Chemotherapy====
| |
| − | *[[Cytarabine (Cytosar)]] 100 mg/m<sup>2</sup>/day IV continuous infusion on days 1 to 10 (total dose: 1000 mg/m<sup>2</sup>)
| |
| − | *[[Daunorubicin (Cerubidine)]] 50 mg/m<sup>2</sup> IV over 5 minutes once per day on days 1, 3, 5
| |
| − | *[[Etoposide (Vepesid)]] 50 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1 to 5
| |
| − | | |
| − | '''10-day course'''
| |
| − | | |
| − | ===References===
| |
| − | # Bishop JF, Matthews JP, Young GA, Szer J, Gillett A, Joshua D, Bradstock K, Enno A, Wolf MM, Fox R, Cobcroft R, Herrmann R, Van Der Weyden M, Lowenthal RM, Page F, Garson OM, Juneja S. A randomized study of high-dose cytarabine in induction in acute myeloid leukemia. Blood. 1996 Mar 1;87(5):1710-7. [http://www.bloodjournal.org/content/87/5/1710.long link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/8634416 PubMed]
| |
| − | # '''UK MRC AML12:''' Burnett AK, Hills RK, Milligan DW, Goldstone AH, Prentice AG, McMullin MF, Duncombe A, Gibson B, Wheatley K. Attempts to optimize induction and consolidation treatment in acute myeloid leukemia: results of the MRC AML12 trial. J Clin Oncol. 2010 Feb 1;28(4):586-95. Epub 2009 Dec 28. [http://ascopubs.org/doi/full/10.1200/JCO.2009.22.9088 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/20038732 PubMed]
| |
| − | # '''UK MRC AML15:''' Burnett AK, Hills RK, Milligan D, Kjeldsen L, Kell J, Russell NH, Yin JA, Hunter A, Goldstone AH, Wheatley K. Identification of patients with acute myeloblastic leukemia who benefit from the addition of gemtuzumab ozogamicin: results of the MRC AML15 trial. J Clin Oncol. 2011 Feb 1;29(4):369-77. Epub 2010 Dec 20. [http://ascopubs.org/doi/10.1200/JCO.2010.31.4310 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/21172891 PubMed]
| |
| − | ## '''Update:''' Burnett AK, Russell NH, Hills RK, Hunter AE, Kjeldsen L, Yin J, Gibson BE, Wheatley K, Milligan D. Optimization of chemotherapy for younger patients with acute myeloid leukemia: results of the MRC AML15 trial. J Clin Oncol. 2013 Sep 20;31(27):3360-8. Epub 2013 Aug 12. [http://jco.ascopubs.org/content/31/27/3360.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/23940227 PubMed]
| |
| − | <!-- Presented at the 53rd American Society of Hematology Annual Meeting and Exposition, San Diego, CA, December 10-13, 2011. -->
| |
| − | # '''EORTC-GIMEMA AML-12:''' Willemze R, Suciu S, Meloni G, Labar B, Marie JP, Halkes CJ, Muus P, Mistrik M, Amadori S, Specchia G, Fabbiano F, Nobile F, Sborgia M, Camera A, Selleslag DL, Lefrère F Sr, Magro D, Sica S, Cantore N, Beksac M, Berneman Z, Thomas X, Melillo L, Guimaraes JE, Leoni P, Luppi M, Mitra ME, Bron D, Fillet G, Marijt EW, Venditti A, Hagemeijer A, Mancini M, Jansen J, Cilloni D, Meert L, Fazi P, Vignetti M, Trisolini SM, Mandelli F, de Witte T. High-dose cytarabine in induction treatment improves the outcome of adult patients younger than age 46 years with acute myeloid leukemia: Results of the EORTC-GIMEMA AML-12 trial. J Clin Oncol. 2014 Jan 20;32(3):219-28. Epub 2013 Dec 2. [http://jco.ascopubs.org/content/32/3/219.full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/24297940 PubMed]
| |
| − | # '''COG AAML0531:''' Gamis AS, Alonzo TA, Meshinchi S, Sung L, Gerbing RB, Raimondi SC, Hirsch BA, Kahwash SB, Heerema-McKenney A, Winter L, Glick K, Davies SM, Byron P, Smith FO, Aplenc R. Gemtuzumab ozogamicin in children and adolescents with de novo acute myeloid leukemia improves event-free survival by reducing relapse risk: results from the randomized phase III Children’s Oncology Group trial AAML0531. J Clin Oncol. 2014 Sep 20;32(27):3021-32. [http://ascopubs.org/doi/full/10.1200/JCO.2014.55.3628 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4162498/ link to PMC article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/25092781 PubMed]
| |
| − | | |
| − | ==ADE (high-dose Ara-C) {{#subobject:c7eb71|Regimen=1}}==
| |
| − | {| class="wikitable" style="float:right; margin-left: 5px;"
| |
| − | |-
| |
| − | |[[#top|back to top]]
| |
| − | |}
| |
| − | ADE: '''<u>A</u>'''ra-C (Cytarabine), '''<u>D</u>'''aunorubicin, '''<u>E</u>'''toposide
| |
| − | <br>HIDAC-3-5: '''<u>HI</u>'''gh-'''<u>D</u>'''ose '''<u>A</u>'''ra-'''<u>C</u>''' (Cytarabine), '''<u>3</u>''' days of Daunorubicin, '''<u>5</u>''' days of Etoposide
| |
| − | <br>HIDAC-3-7: '''<u>HI</u>'''gh-'''<u>D</u>'''ose '''<u>A</u>'''ra-'''<u>C</u>''' (Cytarabine), '''<u>3</u>''' days of Daunorubicin, '''<u>7</u>''' days of Etoposide
| |
| − | ===Variant #1, HIDAC-3-5 {{#subobject:b1a101|Variant=1}}===
| |
| − | {| class="wikitable" style="width: 100%; text-align:center;"
| |
| − | !Study
| |
| − | ![[Levels_of_Evidence#Evidence|Evidence]]
| |
| − | !Comparator
| |
| − | ![[Levels_of_Evidence#Efficacy|Efficacy]]
| |
| − | |-
| |
| − | |[http://jco.ascopubs.org/content/32/3/219.full Willemze et al. 2013 (AML-12)]
| |
| − | | style="background-color:#1a9851" |Phase III (E)
| |
| − | |[[#ADE_.28standard-dose_Ara-C.29|ADE (standard-dose Ara-C)]]
| |
| − | | style="background-color:#d9ef8b" |Might have superior OS
| |
| − | |-
| |
| − | |}
| |
| − | ====Chemotherapy====
| |
| − | *[[Cytarabine (Cytosar)]] 3000 mg/m<sup>2</sup> IV over 3 hours q12h on days 1, 3, 5, 7 (8 doses per cycle)
| |
| − | *[[Daunorubicin (Cerubidine)]] 50 mg/m<sup>2</sup> IV over 5 minutes once per day on days 1, 3, 5
| |
| − | *[[Etoposide (Vepesid)]] 50 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1 to 5
| |
| − | | |
| − | '''7-day course'''
| |
| − | | |
| − | ===Variant #2, HIDAC-3-7 {{#subobject:386df8|Variant=1}}===
| |
| − | {| class="wikitable" style="width: 100%; text-align:center;"
| |
| − | !Study
| |
| − | ![[Levels_of_Evidence#Evidence|Evidence]]
| |
| − | !Comparator
| |
| − | ![[Levels_of_Evidence#Efficacy|Efficacy]]
| |
| − | |-
| |
| − | |[http://www.bloodjournal.org/content/87/5/1710.long Bishop et al. 1996]
| |
| − | | style="background-color:#1a9851" |Phase III (E)
| |
| − | |[[#ADE_.28standard-dose_Ara-C.29|ADE (standard-dose Ara-C)]]
| |
| − | | style="background-color:#1a9850" |Superior DFS
| |
| − | |-
| |
| − | |}
| |
| − | ====Chemotherapy====
| |
| − | *[[Cytarabine (Cytosar)]] 3000 mg/m<sup>2</sup> IV q12h on days 1, 3, 5, 7 (8 doses per cycle)
| |
| − | *[[Daunorubicin (Cerubidine)]] 50 mg/m<sup>2</sup> IV once per day on days 1 to 3
| |
| − | *[[Etoposide (Vepesid)]] 75 mg/m<sup>2</sup> IV once per day on days 1 to 7
| |
| − | | |
| − | '''7-day course, can be repeated up to 3 times if CR not achieved'''
| |
| − | ====Subsequent treatment====
| |
| − | *5-2-5 consolidation x 2
| |
| − | | |
| − | ===References===
| |
| − | # Bishop JF, Matthews JP, Young GA, Szer J, Gillett A, Joshua D, Bradstock K, Enno A, Wolf MM, Fox R, Cobcroft R, Herrmann R, Van Der Weyden M, Lowenthal RM, Page F, Garson OM, Juneja S. A randomized study of high-dose cytarabine in induction in acute myeloid leukemia. Blood. 1996 Mar 1;87(5):1710-7. [http://www.bloodjournal.org/content/87/5/1710.long link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/8634416 PubMed]
| |
| − | <!-- Presented at the 53rd American Society of Hematology Annual Meeting and Exposition, San Diego, CA, December 10-13, 2011. -->
| |
| − | # '''EORTC-GIMEMA AML-12:''' Willemze R, Suciu S, Meloni G, Labar B, Marie JP, Halkes CJ, Muus P, Mistrik M, Amadori S, Specchia G, Fabbiano F, Nobile F, Sborgia M, Camera A, Selleslag DL, Lefrère F Sr, Magro D, Sica S, Cantore N, Beksac M, Berneman Z, Thomas X, Melillo L, Guimaraes JE, Leoni P, Luppi M, Mitra ME, Bron D, Fillet G, Marijt EW, Venditti A, Hagemeijer A, Mancini M, Jansen J, Cilloni D, Meert L, Fazi P, Vignetti M, Trisolini SM, Mandelli F, de Witte T. High-dose cytarabine in induction treatment improves the outcome of adult patients younger than age 46 years with acute myeloid leukemia: Results of the EORTC-GIMEMA AML-12 trial. J Clin Oncol. 2014 Jan 20;32(3):219-28. Epub 2013 Dec 2. [http://jco.ascopubs.org/content/32/3/219.full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/24297940 PubMed]
| |
| − | | |
| − | ==CIA {{#subobject:de6dec|Regimen=1}}==
| |
| − | {| class="wikitable" style="float:right; margin-left: 5px;"
| |
| − | |-
| |
| − | |[[#top|back to top]]
| |
| − | |}
| |
| − | CIA: '''<u>C</u>'''lofarabine, '''<u>I</u>'''darubicin, '''<u>A</u>'''ra-C (Cytarabine)
| |
| − | ===Variant #1, 15/10/1000 {{#subobject:c6c8ec|Variant=1}}===
| |
| − | {| class="wikitable" style="width: 100%; text-align:center;"
| |
| − | !Study
| |
| − | ![[Levels_of_Evidence#Evidence|Evidence]]
| |
| − | !Comparator
| |
| − | ![[Levels_of_Evidence#Efficacy|Efficacy]]
| |
| − | |-
| |
| − | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5739034/ Jabbour et al. 2017]
| |
| − | | style="background-color:#1a9851" |Randomized Phase II (E)
| |
| − | |FIA
| |
| − | | style="background-color:#ffffbf" |Seems not superior
| |
| − | |-
| |
| − | |}
| |
| − | ====Chemotherapy====
| |
| − | *[[Clofarabine (Clolar)]] 15 mg/m<sup>2</sup> IV once per day on days 1 to 5, '''given 4 hours before [[Cytarabine (Cytosar)]]'''
| |
| − | *[[Idarubicin (Idamycin)]] 10 mg/m<sup>2</sup> IV once per day on days 1 to 3
| |
| − | *[[Cytarabine (Cytosar)]] 1000 mg/m<sup>2</sup> IV over 2 hours once per day on days 1 to 5
| |
| − | | |
| − | '''One course'''
| |
| − | ====Subsequent treatment====
| |
| − | *Patients not achieving CR or CRp could undergo a second induction | |
| − | *Patients achieving CR or CRp: [[#CIA_2|CIA consolidation]]
| |
| − | | |
| − | ===Variant #2, 20/10/1000 {{#subobject:4a7d81|Variant=1}}===
| |
| − | {| class="wikitable" style="width: 100%; text-align:center;"
| |
| − | !Study
| |
| − | ![[Levels_of_Evidence#Evidence|Evidence]]
| |
| − | |-
| |
| − | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4110914/ Nazha et al. 2013]
| |
| − | | style="background-color:#91cf61" |Phase II
| |
| − | |-
| |
| − | |}
| |
| − | ====Chemotherapy====
| |
| − | *[[Clofarabine (Clolar)]] 20 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1 to 5
| |
| − | *[[Idarubicin (Idamycin)]] 10 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1 to 3
| |
| − | *[[Cytarabine (Cytosar)]] 1000 mg/m<sup>2</sup> IV over 2 hours once per day on days 1 to 5
| |
| − | | |
| − | ====Supportive medications====
| |
| − | *[[Levofloxacin (Levaquin)]]
| |
| − | *[[Itraconazole (Sporanox)]]
| |
| − | *[[Valacyclovir (Valtrex)]]
| |
| − | *[[:Category:Granulocyte_colony-stimulating_factors|Granulocyte colony-stimulating factor]] neither mandated nor forbidden and given per physician discretion
| |
| − | | |
| − | '''5-day course'''
| |
| − | ====Subsequent treatment====
| |
| − | *Patients with PR: a second course with the same drugs, doses, and schedule.
| |
| − | *Patients achieving CR or CRi: [[#CIA_2|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. Epub 2013 Sep 9. [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4110914/ link to PMC article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/23877926 PubMed]
| |
| − | # Jabbour E, Short NJ, Ravandi F, Huang X, Xiao L, Garcia-Manero G, Plunkett W, Gandhi V, Sasaki K, Pemmaraju N, Daver NG, Borthakur G, Jain N, Konopleva M, Estrov Z, Kadia TM, Wierda WG, DiNardo CD, Brandt M, O'Brien SM, Cortes JE, Kantarjian H. A randomized phase 2 study of idarubicin and cytarabine with clofarabine or fludarabine in patients with newly diagnosed acute myeloid leukemia. Cancer. 2017 Nov 15;123(22):4430-4439. Epub 2017 Jul 14. [https://onlinelibrary.wiley.com/doi/10.1002/cncr.30883/abstract link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5739034/ link to PMC article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/28708931 PubMed]
| |
| − | | |
| − | ==DA 3 + 10, GO {{#subobject:e6f5bb|Regimen=1}}==
| |
| − | {| class="wikitable" style="float:right; margin-left: 5px;"
| |
| − | |-
| |
| − | |[[#top|back to top]]
| |
| − | |}
| |
| − | DA 3 + 10, GO: '''<u>D</u>'''aunorubicin & '''<u>A</u>'''ra-C (Cytarabine), '''<u>3</u>''' days of daunorubicin '''<u>+ 10</u>''' days of cytarabine, '''<u>G</u>'''emtuzumab '''<u>O</u>'''zogamicin
| |
| − | ===Regimen {{#subobject:6a938e|Variant=1}}===
| |
| − | {| class="wikitable" style="width: 100%; text-align:center;"
| |
| − | !Study
| |
| − | ![[Levels_of_Evidence#Evidence|Evidence]]
| |
| − | !Comparator
| |
| − | ![[Levels_of_Evidence#Efficacy|Efficacy]]
| |
| − | |-
| |
| − | |[http://ascopubs.org/doi/10.1200/JCO.2010.31.4310 Burnett et al. 2010 (UK MRC AML15)]
| |
| − | | style="background-color:#1a9851" |Phase III (E)
| |
| − | |See note
| |
| − | |See note
| |
| − | |-
| |
| − | |[http://jco.ascopubs.org/content/30/32/3924.long Burnett et al. 2012 (UK NCRI AML16)]
| |
| − | | style="background-color:#1a9851" |Phase III (E)
| |
| − | |[[#DA_3_.2B_10|DA 3 + 10]]
| |
| − | | style="background-color:#91cf60" |Seems to have superior OS
| |
| − | |-
| |
| − | |}
| |
| − | ''Both trials have complicated treatment schemas; see papers for details.''
| |
| − | ====Chemotherapy====
| |
| − | *[[Cytarabine (Cytosar)]] 100 mg/m<sup>2</sup> IV q12h on days 1 to 10
| |
| − | *[[Daunorubicin (Cerubidine)]] 50 mg/m<sup>2</sup> IV once per day on days 1, 3, 5
| |
| − | *[[Gemtuzumab ozogamicin (Mylotarg)]] 3 mg/m<sup>2</sup> IV once on day 1
| |
| − | | |
| − | '''One course'''
| |
| − | ====Subsequent treatment====
| |
| − | *See paper for details (to be completed).
| |
| − | | |
| − | ===References===
| |
| − | # '''UK MRC AML15:''' Burnett AK, Hills RK, Milligan D, Kjeldsen L, Kell J, Russell NH, Yin JA, Hunter A, Goldstone AH, Wheatley K. Identification of patients with acute myeloblastic leukemia who benefit from the addition of gemtuzumab ozogamicin: results of the MRC AML15 trial. J Clin Oncol. 2011 Feb 1;29(4):369-77. Epub 2010 Dec 20. [http://ascopubs.org/doi/10.1200/JCO.2010.31.4310 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/21172891 PubMed]
| |
| − | ## '''Update:''' Burnett AK, Russell NH, Hills RK, Hunter AE, Kjeldsen L, Yin J, Gibson BE, Wheatley K, Milligan D. Optimization of chemotherapy for younger patients with acute myeloid leukemia: results of the MRC AML15 trial. J Clin Oncol. 2013 Sep 20;31(27):3360-8. Epub 2013 Aug 12. [http://jco.ascopubs.org/content/31/27/3360.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/23940227 PubMed]
| |
| − | # '''UK NCRI AML16:''' Burnett AK, Russell NH, Hills RK, Kell J, Freeman S, Kjeldsen L, Hunter AE, Yin J, Craddock CF, Dufva IH, Wheatley K, Milligan D. Addition of gemtuzumab ozogamicin to induction chemotherapy improves survival in older patients with acute myeloid leukemia. J Clin Oncol. 2012 Nov 10;30(32):3924-31. Epub 2012 Jul 30. [http://jco.ascopubs.org/content/30/32/3924.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/22851554 PubMed]
| |
| − | ## '''Update:''' Burnett AK, Russell NH, Hills RK, Kell J, Nielsen OJ, Dennis M, Cahalin P, Pocock C, Ali S, Burns S, Freeman S, Milligan D, Clark RE. A comparison of clofarabine with ara-C, each in combination with daunorubicin as induction treatment in older patients with acute myeloid leukaemia. Leukemia. 2017 Feb;31(2):310-317. Epub 2016 Sep 2. [https://www.nature.com/leu/journal/v31/n2/fig_tab/leu2016225f1.html link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5292678/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/27624670 PubMed]
| |
| − | | |
| − | ==DA 3 + 10 {{#subobject:5c0062|Regimen=1}}==
| |
| − | {| class="wikitable" style="float:right; margin-left: 5px;"
| |
| − | |-
| |
| − | |[[#top|back to top]]
| |
| − | |}
| |
| − | DA 3 + 10: '''<u>D</u>'''aunorubicin & '''<u>A</u>'''ra-C (Cytarabine), '''<u>3</u>''' days of daunorubicin '''<u>+ 10</u>''' days of cytarabine
| |
| − | ===Variant #1, 50 mg/m<sup>2</sup> dauno {{#subobject:99321e|Variant=1}}===
| |
| − | {| class="wikitable" style="width: 100%; text-align:center;"
| |
| − | !Study
| |
| − | ![[Levels_of_Evidence#Evidence|Evidence]]
| |
| − | !Comparator
| |
| − | ![[Levels_of_Evidence#Efficacy|Efficacy]]
| |
| − | |-
| |
| − | |[http://ascopubs.org/doi/10.1200/JCO.2010.31.4310 Burnett et al. 2010 (UK MRC AML15)]
| |
| − | | style="background-color:#1a9851" |Phase III (C)
| |
| − | |See note
| |
| − | |See note
| |
| − | |-
| |
| − | |[http://jco.ascopubs.org/content/30/32/3924.long Burnett et al. 2012 (UK NCRI AML16)]
| |
| − | | style="background-color:#1a9851" |Phase III (C)
| |
| − | |[[#DA_3_.2B_10.2C_GO|DA 3 + 10, GO]]
| |
| − | | style="background-color:#fc8d59" |Seems to have inferior OS
| |
| − | |-
| |
| − | |}
| |
| − | ''Note: this regimen is very similar to [[#7.2B3d_.28standard-dose.29|7+3d (standard-dose)]]; however, 1) there is slightly more cytarabine given, in an intermittent schedule, and 2) the daunorubicin is given intermittently over 5 days, not 3. Both trials have complicated treatment schemas; see papers for details.''
| |
| − | ====Chemotherapy====
| |
| − | *[[Cytarabine (Cytosar)]] 100 mg/m<sup>2</sup> IV q12h on days 1 to 10
| |
| − | *[[Daunorubicin (Cerubidine)]] 50 mg/m<sup>2</sup> IV once per day on days 1, 3, 5
| |
| − | | |
| − | '''One course'''
| |
| − | ====Subsequent treatment====
| |
| − | *See papers for details (to be completed).
| |
| − | | |
| − | ===Variant #2, 60 mg/m<sup>2</sup> dauno {{#subobject:211741|Variant=1}}===
| |
| − | {| class="wikitable" style="width: 100%; text-align:center;"
| |
| − | !Study
| |
| − | ![[Levels_of_Evidence#Evidence|Evidence]]
| |
| − | !Comparator
| |
| − | ![[Levels_of_Evidence#Efficacy|Efficacy]]
| |
| − | |-
| |
| − | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4505010/ Burnett et al. 2015 (UK NCRI AML17)]
| |
| − | | style="background-color:#1a9851" |Phase III (C)
| |
| − | |DA 3 + 10 (high-dose)
| |
| − | | style="background-color:#ffffbf" |Seems not superior
| |
| − | |-
| |
| − | |}
| |
| − | ''Note: this regimen is very similar to [[#7.2B3d_.28intermediate-dose.29|7+3d (intermediate-dose)]]; however, 1) there is slightly more cytarabine given, in an intermittent schedule, and 2) the daunorubicin is given intermittently over 5 days, not 3.''
| |
| − | ====Chemotherapy====
| |
| − | *[[Cytarabine (Cytosar)]] 100 mg/m<sup>2</sup> IV q12h on days 1 to 10
| |
| − | *[[Daunorubicin (Cerubidine)]] 60 mg/m<sup>2</sup> IV once per day on days 1, 3, 5
| |
| − | | |
| − | '''One course'''
| |
| − | ====Subsequent treatment====
| |
| − | *Complex randomization; see paper for details (to be completed).
| |
| − | | |
| − | ===References===
| |
| − | # '''UK MRC AML15:''' Burnett AK, Hills RK, Milligan D, Kjeldsen L, Kell J, Russell NH, Yin JA, Hunter A, Goldstone AH, Wheatley K. Identification of patients with acute myeloblastic leukemia who benefit from the addition of gemtuzumab ozogamicin: results of the MRC AML15 trial. J Clin Oncol. 2011 Feb 1;29(4):369-77. Epub 2010 Dec 20. [http://ascopubs.org/doi/10.1200/JCO.2010.31.4310 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/21172891 PubMed]
| |
| − | ## '''Update:''' Burnett AK, Russell NH, Hills RK, Hunter AE, Kjeldsen L, Yin J, Gibson BE, Wheatley K, Milligan D. Optimization of chemotherapy for younger patients with acute myeloid leukemia: results of the MRC AML15 trial. J Clin Oncol. 2013 Sep 20;31(27):3360-8. Epub 2013 Aug 12. [http://jco.ascopubs.org/content/31/27/3360.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/23940227 PubMed]
| |
| − | # '''UK NCRI AML16:''' Burnett AK, Russell NH, Hills RK, Kell J, Freeman S, Kjeldsen L, Hunter AE, Yin J, Craddock CF, Dufva IH, Wheatley K, Milligan D. Addition of gemtuzumab ozogamicin to induction chemotherapy improves survival in older patients with acute myeloid leukemia. J Clin Oncol. 2012 Nov 10;30(32):3924-31. Epub 2012 Jul 30. [http://jco.ascopubs.org/content/30/32/3924.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/22851554 PubMed]
| |
| − | ## '''Update:''' Burnett AK, Russell NH, Hills RK, Kell J, Nielsen OJ, Dennis M, Cahalin P, Pocock C, Ali S, Burns S, Freeman S, Milligan D, Clark RE. A comparison of clofarabine with ara-C, each in combination with daunorubicin as induction treatment in older patients with acute myeloid leukaemia. Leukemia. 2017 Feb;31(2):310-317. Epub 2016 Sep 2. [https://www.nature.com/leu/journal/v31/n2/fig_tab/leu2016225f1.html link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5292678/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/27624670 PubMed]
| |
| − | # '''UK NCRI AML17:''' Burnett AK, Russell NH, Hills RK, Kell J, Cavenagh J, Kjeldsen L, McMullin MF, Cahalin P, Dennis M, Friis L, Thomas IF, Milligan D, Clark RE; UK NCRI AML Study Group. A randomized comparison of daunorubicin 90 mg/m<sup>2</sup> vs 60 mg/m<sup>2</sup> in AML induction: results from the UK NCRI AML17 trial in 1206 patients. Blood. 2015 Jun 18;125(25):3878-85. Epub 2015 Apr 1. [http://www.bloodjournal.org/content/125/25/3878.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4505010/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/25833957 PubMed]
| |
| − | | |
| − | ==DAC {{#subobject:9b1553|Regimen=1}}==
| |
| − | {| class="wikitable" style="float:right; margin-left: 5px;"
| |
| − | |-
| |
| − | |[[#top|back to top]]
| |
| − | |}
| |
| − | DAC: '''<u>D</u>'''aunorubicin, '''<u>A</u>'''ra-C (Cytarabine), '''<u>C</u>'''ladribine
| |
| − | ===Regimen {{#subobject:f00b8a|Variant=1}}===
| |
| − | {| class="wikitable" style="width: 100%; text-align:center;"
| |
| − | !Study
| |
| − | ![[Levels_of_Evidence#Evidence|Evidence]]
| |
| − | !Comparator
| |
| − | ![[Levels_of_Evidence#Efficacy|Efficacy]]
| |
| − | |-
| |
| − | |[https://www.nature.com/leu/journal/v18/n5/full/2403336a.html Holowiecki et al. 2004 (PALG AML1/1999)]
| |
| − | | style="background-color:#1a9851" |Phase III (E)
| |
| − | |[[#7.2B3d_.28intermediate-dose.29|DA]]
| |
| − | | style="background-color:#1a9850" |Superior CR rate after first induction
| |
| − | |-
| |
| − | | rowspan="2" |[http://jco.ascopubs.org/content/30/20/2441.full Holowiecki et al. 2012 (PALG AML1/2004)]
| |
| − | | rowspan="2" style="background-color:#1a9851" |Phase III (E)
| |
| − | |[[#7.2B3d_.28intermediate-dose.29|DA]]
| |
| − | | style="background-color:#1a9850" |Superior OS
| |
| − | |-
| |
| − | |DAF
| |
| − | | style="background-color:#91cf60" |Seems to have superior OS
| |
| − | |-
| |
| − | |}
| |
| − | ====Chemotherapy====
| |
| − | *[[Daunorubicin (Cerubidine)]] 60 mg/m<sup>2</sup> IV over 5 minutes once per day on days 1 to 3
| |
| − | *[[Cytarabine (Cytosar)]] 200 mg/m<sup>2</sup>/day IV continuous infusion on days 1 to 7 (total dose: 1400 mg/m<sup>2</sup>)
| |
| − | *[[Cladribine (Leustatin)]] 5 mg/m<sup>2</sup> IV over 3 hours once per day on days 1 to 5
| |
| − | | |
| − | ====Supportive medications====
| |
| − | *"According to commonly accepted guidelines with no prophylactic IV antibiotics"
| |
| − | *[[:Category:Granulocyte_colony-stimulating_factors|Granulocyte colony-stimulating factor]] recommended only for patients older than 50 years old whose leukemic blasts were negative for CD114 expression
| |
| − | | |
| − | '''7-day course'''
| |
| − | ====Subsequent treatment====
| |
| − | *Patients with only partial remission in both studies underwent a second course with the same drugs, doses, and schedule.
| |
| − | *Non-responders in PALG AML1/1999: [[#CLAG|CLAG salvage]]
| |
| − | *Patients in remission in both studies: [[#HAM|HAM]], then [[#HiDAC|HiDAC]] consolidation
| |
| − | | |
| − | ===References===
| |
| − | # '''PALG AML1/1999:''' Holowiecki J, Grosicki S, Robak T, Kyrcz-Krzemien S, Giebel S, Hellmann A, Skotnicki A, Jedrzejczak WW, Konopka L, Kuliczkowski K, Zdziarska B, Dmoszyńska A, Marianska B, Pluta A, Zawilska K, Komarnicki M, Kloczko J, Sulek K, Haus O, Stella-Holowiecka B, Baran W, Jakubas B, Paluszewska M, Wierzbowska A, Kielbinski M, Jagoda K; Polish Adult Leukemia Group (PALG). Addition of cladribine to daunorubicin and cytarabine increases complete remission rate after a single course of induction treatment in acute myeloid leukemia: multicenter, phase III study. Leukemia. 2004 May;18(5):989-97. [https://www.nature.com/leu/journal/v18/n5/full/2403336a.html link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/14999298 PubMed]
| |
| − | # '''PALG AML1/2004:''' Holowiecki J, Grosicki S, Giebel S, Robak T, Kyrcz-Krzemien S, Kuliczkowski K, Skotnicki AB, Hellmann A, Sulek K, Dmoszyńska 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. J Clin Oncol. 2012 Jul 10;30(20):2441-8. Epub 2012 Apr 16. [http://jco.ascopubs.org/content/30/20/2441.full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/22508825 PubMed]
| |
| − | | |
| − | ==FLAG-Ida {{#subobject:7fc219|Regimen=1}}==
| |
| − | {| class="wikitable" style="float:right; margin-left: 5px;"
| |
| − | |-
| |
| − | |[[#top|back to top]]
| |
| − | |}
| |
| − | FLAG-Ida: '''<u>FL</u>'''udarabine, '''<u>A</u>'''ra-C (Cytarabine), '''<u>G</u>'''-CSF (Lenograstim), '''<u>Ida</u>'''rubicin
| |
| − | ===Regimen {{#subobject:44e85e|Variant=1}}===
| |
| − | {| class="wikitable" style="width: 100%; text-align:center;"
| |
| − | !Study
| |
| − | ![[Levels_of_Evidence#Evidence|Evidence]]
| |
| − | |-
| |
| − | |[http://ascopubs.org/doi/10.1200/JCO.2010.31.4310 Burnett et al. 2010 (UK MRC AML15)]
| |
| − | | style="background-color:#1a9851" |Phase III (*)
| |
| − | |-
| |
| − | |}
| |
| − | ''This trial has a complex randomization; to be completed.''
| |
| − | ====Chemotherapy====
| |
| − | *[[Fludarabine (Fludara)]] 30 mg/m<sup>2</sup> IV once per day on days 2 to 6
| |
| − | *[[Cytarabine (Cytosar)]] 2000 mg/m<sup>2</sup> IV over 4 hours once per day on days 2 to 6, given 4 hours after [[Fludarabine (Fludara)]]
| |
| − | *[[Lenograstim (Granocyte)]] 263 mcg SC once per day on days 1 to 7
| |
| − | *[[Idarubicin (Idamycin)]] 8 mg/m<sup>2</sup> IV once per day on days 4 to 6
| |
| − | | |
| − | '''One course'''
| |
| − | ====Subsequent treatment====
| |
| − | *See paper for details
| |
| − | ===References===
| |
| − | # '''UK MRC AML15:''' Burnett AK, Hills RK, Milligan D, Kjeldsen L, Kell J, Russell NH, Yin JA, Hunter A, Goldstone AH, Wheatley K. Identification of patients with acute myeloblastic leukemia who benefit from the addition of gemtuzumab ozogamicin: results of the MRC AML15 trial. J Clin Oncol. 2011 Feb 1;29(4):369-77. Epub 2010 Dec 20. [http://ascopubs.org/doi/10.1200/JCO.2010.31.4310 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/21172891 PubMed]
| |
| − | ## '''Update:''' Burnett AK, Russell NH, Hills RK, Hunter AE, Kjeldsen L, Yin J, Gibson BE, Wheatley K, Milligan D. Optimization of chemotherapy for younger patients with acute myeloid leukemia: results of the MRC AML15 trial. J Clin Oncol. 2013 Sep 20;31(27):3360-8. Epub 2013 Aug 12. [http://jco.ascopubs.org/content/31/27/3360.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/23940227 PubMed]
| |
| − | | |
| − | ==HAA {{#subobject:0788e0|Regimen=1}}==
| |
| − | {| class="wikitable" style="float:right; margin-left: 5px;"
| |
| − | |-
| |
| − | |[[#top|back to top]]
| |
| − | |}
| |
| − | HAA: '''<u>H</u>'''omoharringtonine (Omacetaxine), '''<u>A</u>'''ra-C (Cytarabine), '''<u>A</u>'''clarubicin
| |
| − | ===Regimen {{#subobject:5c5c2e|Variant=1}}===
| |
| − | {| class="wikitable" style="width: 100%; text-align:center;"
| |
| − | !Study
| |
| − | ![[Levels_of_Evidence#Evidence|Evidence]]
| |
| − | !Comparator
| |
| − | ![[Levels_of_Evidence#Efficacy|Efficacy]]
| |
| − | |-
| |
| − | | rowspan="2" |[https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(13)70152-9/fulltext Jin et al. 2013]
| |
| − | | rowspan="2" style="background-color:#1a9851" |Phase III (E)
| |
| − | |[[#7.2B3d_.28standard-dose.29|DA]]
| |
| − | | style="background-color:#1a9850" |Superior EFS
| |
| − | |-
| |
| − | |[[#HAD|HAD]]
| |
| − | | style="background-color:#d3d3d3" |Not reported
| |
| − | |-
| |
| − | |}
| |
| − | ''Unlikely to be completed since there were significantly more deaths in this arm, despite a superior primary efficacy endpoint.''
| |
| − | ====Chemotherapy====
| |
| − | *[[Omacetaxine (Synribo)]]
| |
| − | *[[Cytarabine (Cytosar)]]
| |
| − | *[[Aclarubicin (Aclacinon)]]
| |
| − | ===References===
| |
| − | # Jin J, Wang JX, Chen FF, Wu DP, Hu J, Zhou JF, Hu JD, Wang JM, Li JY, Huang XJ, Ma J, Ji CY, Xu XP, Yu K, Ren HY, Zhou YH, Tong Y, Lou YJ, Ni WM, Tong HY, Wang HF, Mi YC, Du X, Chen BA, Shen Y, Chen Z, Chen SJ. Homoharringtonine-based induction regimens for patients with de-novo acute myeloid leukaemia: a multicentre, open-label, randomised, controlled phase 3 trial. Lancet Oncol. 2013 Jun;14(7):599-608. Epub 2013 May 9. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(13)70152-9/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/23664707 PubMed]
| |
| − | | |
| − | ==HAD {{#subobject:30f8fa|Regimen=1}}==
| |
| − | {| class="wikitable" style="float:right; margin-left: 5px;"
| |
| − | |-
| |
| − | |[[#top|back to top]]
| |
| − | |}
| |
| − | HAD: '''<u>H</u>'''omoharringtonine (Omacetaxine), '''<u>A</u>'''ra-C (Cytarabine), '''<u>D</u>'''aunorubicin
| |
| − | ===Regimen {{#subobject:1d644a|Variant=1}}===
| |
| − | {| class="wikitable" style="width: 100%; text-align:center;"
| |
| − | !Study
| |
| − | ![[Levels_of_Evidence#Evidence|Evidence]]
| |
| − | !Comparator
| |
| − | ![[Levels_of_Evidence#Efficacy|Efficacy]]
| |
| − | |-
| |
| − | | rowspan="2" |[https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(13)70152-9/fulltext Jin et al. 2013]
| |
| − | | rowspan="2" style="background-color:#1a9851" |Phase III (E)
| |
| − | |[[#7.2B3d_.28standard-dose.29|DA]]
| |
| − | | style="background-color:#d9ef8b" |Might have superior EFS
| |
| − | |-
| |
| − | |[[#HAA|HAA]]
| |
| − | | style="background-color:#d3d3d3" |Not reported
| |
| − | |-
| |
| − | |}
| |
| − | ''Unlikely to be completed since there were significantly more deaths in this arm, despite a trend towards a superior primary efficacy endpoint.''
| |
| − | ====Chemotherapy====
| |
| − | *[[Omacetaxine (Synribo)]]
| |
| − | *[[Cytarabine (Cytosar)]]
| |
| − | *[[Daunorubicin (Cerubidine)]]
| |
| − | ===References===
| |
| − | # Jin J, Wang JX, Chen FF, Wu DP, Hu J, Zhou JF, Hu JD, Wang JM, Li JY, Huang XJ, Ma J, Ji CY, Xu XP, Yu K, Ren HY, Zhou YH, Tong Y, Lou YJ, Ni WM, Tong HY, Wang HF, Mi YC, Du X, Chen BA, Shen Y, Chen Z, Chen SJ. Homoharringtonine-based induction regimens for patients with de-novo acute myeloid leukaemia: a multicentre, open-label, randomised, controlled phase 3 trial. Lancet Oncol. 2013 Jun;14(7):599-608. Epub 2013 May 9. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(13)70152-9/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/23664707 PubMed]
| |
| − | | |
| − | ==MEC {{#subobject:324735|Regimen=1}}==
| |
| − | {| class="wikitable" style="float:right; margin-left: 5px;"
| |
| − | |-
| |
| − | |[[#top|back to top]]
| |
| − | |}
| |
| − | MEC: '''<u>M</u>'''itoxantrone, '''<u>E</u>'''toposide, '''<u>C</u>'''ytarabine
| |
| − | <br>MICE: '''<u>MI</u>'''toxantrone, '''<u>C</u>'''ytarabine, '''<u>E</u>'''toposide
| |
| − | ===Regimen {{#subobject:33e408|Variant=1}}===
| |
| − | {| class="wikitable" style="width: 100%; text-align:center;"
| |
| − | !Study
| |
| − | ![[Levels_of_Evidence#Evidence|Evidence]]
| |
| − | !Comparator
| |
| − | ![[Levels_of_Evidence#Efficacy|Efficacy]]
| |
| − | |-
| |
| − | |[http://ascopubs.org/doi/full/10.1200/JCO.2013.49.0771 Amadori et al. 2013 (EORTC/GIMEMA AML-17)]
| |
| − | | style="background-color:#1a9851" |Phase III (C)
| |
| − | |GO, then MICE
| |
| − | | style="background-color:#d9ef8b" |Might have superior OS
| |
| − | |-
| |
| − | |}
| |
| − | ====Chemotherapy====
| |
| − | *[[Mitoxantrone (Novantrone)]] 7 mg/m<sup>2</sup> IV once per day on days 1, 3, 5
| |
| − | *[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV once per day on days 1 to 3
| |
| − | *[[Cytarabine (Cytosar)]] 100 mg/m<sup>2</sup>/day IV continuous infusion on days 1 to 7 (total dose: 700 mg/m<sup>2</sup>)
| |
| − | | |
| − | '''One course'''
| |
| | | | |
| | ===References=== | | ===References=== |
| − | # '''EORTC/GIMEMA AML-17:''' Amadori S, Suciu S, Stasi R, Salih HR, Selleslag D, Muus P, De Fabritiis P, Venditti A, Ho AD, Lübbert M, Thomas X, Latagliata R, Halkes CJ, Falzetti F, Magro D, Guimaraes JE, Berneman Z, Specchia G, Karrasch M, Fazi P, Vignetti M, Willemze R, de Witte T, Marie JP. Sequential combination of gemtuzumab ozogamicin and standard chemotherapy in older patients with newly diagnosed acute myeloid leukemia: results of a randomized phase III trial by the EORTC and GIMEMA consortium (AML-17). J Clin Oncol. 2013 Dec 10;31(35):4424-30. Epub 2013 Oct 14. [http://ascopubs.org/doi/full/10.1200/JCO.2013.49.0771 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/24127442 PubMed] | + | # '''CALGB 11001:''' Uy GL, Mandrekar SJ, Laumann K, Marcucci G, Zhao W, Levis MJ, Klepin HD, Baer MR, Powell BL, Westervelt P, DeAngelo DJ, Stock W, Sanford B, Blum WG, Bloomfield CD, Stone RM, Larson RA. A phase 2 study incorporating sorafenib into the chemotherapy for older adults with FLT3-mutated acute myeloid leukemia: CALGB 11001. Blood Adv. 2017 Jan 24;1(5):331-340. [http://www.bloodadvances.org/content/1/5/331 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5637402/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/29034366 PubMed] |
| − | | |
| − | =First-line induction therapy, older or "unfit" patients=
| |
| − | ''Note: these regimens are generally considered to be part of a non-curative line of treatment.''
| |
| − | ==7+3i & Panobinostat {{#subobject:59e8a8|Regimen=1}}==
| |
| − | {| class="wikitable" style="float:right; margin-left: 5px;"
| |
| − | |-
| |
| − | |[[#top|back to top]]
| |
| − | |}
| |
| − | 7+3i & Panobinostat: '''<u>7</u>''' days of cytarabine + '''<u>3</u>''' days of '''<u>i</u>'''darubicin, Panobinostat
| |
| − | | |
| − | ===Regimen {{#subobject:ccacb0|Variant=1}}===
| |
| − | {| class="wikitable" style="width: 100%; text-align:center;"
| |
| − | !Study
| |
| − | ![[Levels_of_Evidence#Evidence|Evidence]]
| |
| − | ![[Levels_of_Evidence#Efficacy|Efficacy]]
| |
| − | |-
| |
| − | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4591761/ Ocio et al. 2015 (panobidara)]
| |
| − | | style="background-color:#91cf61" |Phase II
| |
| − | | style="background-color:#bfd3e6" |CR rate: 64%
| |
| − | |-
| |
| − | |}
| |
| − | | |
| − | ''Note that the dose of idarubicin is lower than that used in standard 7+3i. The panobinostat dose is the MTD in this phase Ib/II study.''
| |
| − | ====Chemotherapy====
| |
| − | *[[Cytarabine (Cytosar)]] 100 mg/m<sup>2</sup>/day IV continuous infusion on days 1 to 7 (total dose: 700 mg/m<sup>2</sup>)
| |
| − | *[[Idarubicin (Idamycin)]] 8 mg/m<sup>2</sup> IV once per day on days 1 to 3
| |
| − | *[[Panobinostat (Farydak)]] 10 mg PO once per day on days 8, 10, 12, 15, 17, 19
| |
| − | | |
| − | '''One course'''
| |
| − | ====Subsequent treatment====
| |
| − | *Non-responders could undergo an identical second cycle.
| |
| − | *Responders proceeded to receive the same regimen in consolidation (one course), then [[#Panobinostat_monotherapy|panobinostat maintenance]]
| |
| − | | |
| − | ===References===
| |
| − | # '''panobidara:''' Ocio EM, Herrera P, Olave MT, Castro N, Pérez-Simón JA, Brunet S, Oriol A, Mateo M, Sanz MÁ, López J, Montesinos P, Chillón MC, Prieto-Conde MI, Díez-Campelo M, González M, Vidriales MB, Mateos MV, San Miguel JF; PETHEMA Group. Panobinostat as part of induction and maintenance for elderly patients with newly diagnosed acute myeloid leukemia: phase Ib/II panobidara study. Haematologica. 2015 Oct;100(10):1294-300. Epub 2015 Jul 9. [http://www.haematologica.org/content/100/10/1294 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4591761/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/26160880 PubMed]
| |
| − | | |
| − | ==Azacitidine monotherapy {{#subobject:791718|Regimen=1}}==
| |
| − | {| class="wikitable" style="float:right; margin-left: 5px;"
| |
| − | |-
| |
| − | |[[#top|back to top]]
| |
| − | |}
| |
| − | ===Regimen {{#subobject:7509ab|Variant=1}}===
| |
| − | {| class="wikitable" style="width: 100%; text-align:center;"
| |
| − | !Study
| |
| − | ![[Levels_of_Evidence#Evidence|Evidence]]
| |
| − | !Comparator
| |
| − | ![[Levels_of_Evidence#Efficacy|Efficacy]]
| |
| − | |-
| |
| − | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4504945/ Dombret et al. 2015 (AZA-AML-001)]
| |
| − | | style="background-color:#1a9851" |Phase III (E)
| |
| − | |Investigator's choice of:<br> [[#7.2B3d_.28standard-dose.29|7+3d (standard-dose)]]<br> [[#7.2B3d_.28intermediate-dose.29|7+3d (intermediate-dose)]]<br> [[#7.2B3i|7+3i]]<br> [[#Best_supportive_care|Best supportive care]]<br> [[#LoDAC|LoDAC]]
| |
| − | | style="background-color:#d9ef8b" |Might have superior OS
| |
| − | |-
| |
| − | |}
| |
| − | ====Chemotherapy====
| |
| − | *[[Azacitidine (Vidaza)]] 75 mg/m<sup>2</sup> SC once per day on days 1 to 7
| |
| − | | |
| − | '''28-day cycle for at least 6 cycles'''
| |
| − | | |
| − | ===References===
| |
| − | # '''AZA-AML-001:''' Dombret H, Seymour JF, Butrym A, Wierzbowska A, Selleslag D, Jang JH, Kumar R, Cavenagh J, Schuh AC, Candoni A, Récher C, Sandhu I, Bernal Del Castillo T, Al-Ali HK, Martinelli G, Falantes J, Noppeney R, Stone RM, Minden MD, McIntyre H, Songer S, Lucy LM, Beach CL, Döhner H. International phase 3 study of azacitidine vs conventional care regimens in older patients with newly diagnosed AML with >30% blasts. Blood. 2015 Jul 16;126(3):291-9. Epub 2015 May 18. [http://www.bloodjournal.org/content/126/3/291.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4504945/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/25987659 PubMed]
| |
| − | ## '''Subgroup analysis:''' Seymour JF, Döhner H, Butrym A, Wierzbowska A, Selleslag D, Jang JH, Kumar R, Cavenagh J, Schuh AC, Candoni A, Récher C, Sandhu I, Del Castillo TB, Al-Ali HK, Falantes J, Stone RM, Minden MD, Weaver J, Songer S, Beach CL, Dombret H. Azacitidine improves clinical outcomes in older patients with acute myeloid leukaemia with myelodysplasia-related changes compared with conventional care regimens. BMC Cancer. 2017 Dec 14;17(1):852. [https://bmccancer.biomedcentral.com/articles/10.1186/s12885-017-3803-6 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5731212/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/29241450 PubMed]
| |
| − | | |
| − | ==Azacitidine & Gemtuzumab ozogamicin {{#subobject:6f77be|Regimen=1}}==
| |
| − | {| class="wikitable" style="float:right; margin-left: 5px;"
| |
| − | |-
| |
| − | |[[#top|back to top]]
| |
| − | |}
| |
| − | ===Regimen {{#subobject:188f5c|Variant=1}}===
| |
| − | {| class="wikitable" style="width: 100%; text-align:center;"
| |
| − | !Study
| |
| − | ![[Levels_of_Evidence#Evidence|Evidence]]
| |
| − | |-
| |
| − | |[https://www.tandfonline.com/doi/full/10.1080/10428190802451254 Nand et al. 2008]
| |
| − | | style="background-color:#91cf61" |Phase II
| |
| − | |-
| |
| − | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3829116/ Nand et al. 2013 (SWOG S0703)]
| |
| − | | style="background-color:#91cf61" |Phase II
| |
| − | |-
| |
| − | |}
| |
| − | | |
| − | ''Patients with WBC greater than 10 x 10<sup>9</sup>/L at presentation were pre-treated with Hydrea. Leukapheresis was recommended for patients with WBC greater than x 10<sup>9</sup>/L. Nand et al. 2008 did not describe the maintenance portion of the regimen, and used only SC azacitidine.''
| |
| − | | |
| − | ====Chemotherapy, pre-treatment phase====
| |
| − | *[[Hydroxyurea (Hydrea)]] 1500 mg PO twice per day or "in higher doses if necessary"
| |
| − | | |
| − | '''Once WBC is less than 10 x 10<sup>9</sup>/L, stop Hydrea and proceed:'''
| |
| − | | |
| − | ====Chemotherapy, induction====
| |
| − | *[[Azacitidine (Vidaza)]] 75 mg/m<sup>2</sup> SC or IV once per day on days 1 to 7
| |
| − | *[[Gemtuzumab ozogamicin (Mylotarg)]] 3 mg/m<sup>2</sup> IV once on day 8
| |
| − | | |
| − | ====Supportive medications====
| |
| − | *"Appropriate premedications" which were not specified, for [[Gemtuzumab ozogamicin (Mylotarg)]]
| |
| − | ====Subsequent treatment====
| |
| − | *If D14 bone marrow with 5% or more blasts, a second induction cycle identical to the first was administered
| |
| − | *Patients achieving CR or CRi: [[#Azacitidine_.26_Gemtuzumab_ozogamicin_2|Azacitidine and gemtuzumab ozogamicin consolidation]], within 60 days
| |
| − | | |
| − | ===References===
| |
| − | # Nand S, Godwin J, Smith S, Barton K, Michaelis L, Alkan S, Veerappan R, Rychlik K, Germano E, Stiff P. Hydroxyurea, azacitidine and gemtuzumab ozogamicin therapy in patients with previously untreated non-M3 acute myeloid leukemia and high-risk myelodysplastic syndromes in the elderly: results from a pilot trial. Leuk Lymphoma. 2008 Nov;49(11):2141-7. [https://www.tandfonline.com/doi/full/10.1080/10428190802451254 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/19021057 PubMed]
| |
| − | <!-- Presented in part at the American Society of Clinical Oncology annual meeting (Chicago, IL, June 1-5, 2012) and at the American Society of Hematology annual meeting (Atlanta, GA, December 8-11, 2012). -->
| |
| − | # '''SWOG S0703:''' Nand S, Othus M, Godwin JE, Willman CL, Norwood TH, Howard DS, Coutre SE, Erba HP, Appelbaum FR. A phase 2 trial of azacitidine and gemtuzumab ozogamicin therapy in older patients with acute myeloid leukemia. Blood. 2013 Nov 14;122(20):3432-9. Epub 2013 Oct 3. [http://www.bloodjournal.org/content/122/20/3432.full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3829116/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/24092933 PubMed]
| |
| − | | |
| − | ==Best supportive care==
| |
| − | {| class="wikitable" style="float:right; margin-left: 5px;"
| |
| − | |-
| |
| − | |[[#top|back to top]]
| |
| − | |}
| |
| − | ===Regimen===
| |
| − | {| class="wikitable" style="width: 100%; text-align:center;"
| |
| − | !Study
| |
| − | ![[Levels_of_Evidence#Evidence|Evidence]]
| |
| − | !Comparator
| |
| − | ![[Levels_of_Evidence#Efficacy|Efficacy]]
| |
| − | |-
| |
| − | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4874148/ Kantarjian et al. 2012]
| |
| − | | style="background-color:#1a9851" |Phase III (C)
| |
| − | |[[#Decitabine_monotherapy|Decitabine]]
| |
| − | | style="background-color:#fee08b" |Might have inferior OS
| |
| − | |-
| |
| − | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4504945/ Dombret et al. 2015 (AZA-AML-001)]
| |
| − | | style="background-color:#1a9851" |Phase III (C)
| |
| − | |[[#Azacitidine_monotherapy|Azacitidine]]
| |
| − | | style="background-color:#fee08b" |Might have inferior OS
| |
| − | |-
| |
| − | |[http://jco.ascopubs.org/content/34/9/972.full Amadori et al. 2016 (EORTC/GIMEMA AML-19)]
| |
| − | | style="background-color:#1a9851" |Phase III (C)
| |
| − | |Gemtuzumab ozogamicin
| |
| − | | style="background-color:#d73027" |Inferior OS
| |
| − | |-
| |
| − | |}
| |
| − | ''No active antineoplastic treatment, although some trials consider [[Hydroxyurea (Hydrea)]] to be a component of best supportive care.''
| |
| − | | |
| − | ===References===
| |
| − | <!-- Presented in part at the 47th Annual Meeting of the American Society of Clinical Oncology, Chicago, IL, June 3-7, 2011. -->
| |
| − | # Kantarjian HM, Thomas XG, Dmoszyńska 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. Epub 2012 Jun 11. [http://jco.ascopubs.org/content/30/21/2670.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4874148/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/22689805 PubMed]
| |
| − | # '''AZA-AML-001:''' Dombret H, Seymour JF, Butrym A, Wierzbowska A, Selleslag D, Jang JH, Kumar R, Cavenagh J, Schuh AC, Candoni A, Récher C, Sandhu I, Bernal Del Castillo T, Al-Ali HK, Martinelli G, Falantes J, Noppeney R, Stone RM, Minden MD, McIntyre H, Songer S, Lucy LM, Beach CL, Döhner H. International phase 3 study of azacitidine vs conventional care regimens in older patients with newly diagnosed AML with >30% blasts. Blood. 2015 Jul 16;126(3):291-9. Epub 2015 May 18. [http://www.bloodjournal.org/content/126/3/291.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4504945/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/25987659 PubMed]
| |
| − | ## '''Subgroup analysis:''' Seymour JF, Döhner H, Butrym A, Wierzbowska A, Selleslag D, Jang JH, Kumar R, Cavenagh J, Schuh AC, Candoni A, Récher C, Sandhu I, Del Castillo TB, Al-Ali HK, Falantes J, Stone RM, Minden MD, Weaver J, Songer S, Beach CL, Dombret H. Azacitidine improves clinical outcomes in older patients with acute myeloid leukaemia with myelodysplasia-related changes compared with conventional care regimens. BMC Cancer. 2017 Dec 14;17(1):852. [https://bmccancer.biomedcentral.com/articles/10.1186/s12885-017-3803-6 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5731212/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/29241450 PubMed]
| |
| − | <!-- Presented in part at the 56th Annual Meeting of the American Society of Hematology, San Francisco, CA, December 6-9, 2014. -->
| |
| − | # '''EORTC-GIMEMA AML-19:''' Amadori S, Suciu S, Selleslag D, Aversa F, Gaidano G, Musso M, Annino L, Venditti A, Voso MT, Mazzone C, Magro D, De Fabritiis P, Muus P, Alimena G, Mancini M, Hagemeijer A, Paoloni F, Vignetti M, Fazi P, Meert L, Ramadan SM, Willemze R, de Witte T, Baron F. Gemtuzumab ozogamicin versus best supportive care in older patients with newly diagnosed acute myeloid leukemia unsuitable for intensive chemotherapy: results of the randomized phase III EORTC-GIMEMA AML-19 trial. J Clin Oncol. 2016 Mar 20;34(9):972-9. Epub 2016 Jan 25. [http://jco.ascopubs.org/content/34/9/972.full link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/26811524 PubMed]
| |
| − | | |
| − | ==Clofarabine monotherapy {{#subobject:18ac50|Regimen=1}}==
| |
| − | {| class="wikitable" style="float:right; margin-left: 5px;"
| |
| − | |-
| |
| − | |[[#top|back to top]]
| |
| − | |}
| |
| − | ===Regimen {{#subobject:f9ef00|Variant=1}}===
| |
| − | {| class="wikitable" style="width: 100%; text-align:center;"
| |
| − | !Study
| |
| − | ![[Levels_of_Evidence#Evidence|Evidence]]
| |
| − | !Comparator
| |
| − | ![[Levels_of_Evidence#Efficacy|Efficacy]]
| |
| − | |-
| |
| − | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4081352/ Faderl et al. 2008]
| |
| − | | style="background-color:#1a9851" |Randomized Phase II (E)
| |
| − | |[[#Clofarabine_.26_LoDAC|Clofarabine & LoDAC]]
| |
| − | | style="background-color:#fc8d59" |Seems to have inferior EFS
| |
| − | |-
| |
| − | |[http://ascopubs.org/doi/full/10.1200/JCO.2009.26.4242 Burnett et al. 2010 (UWCM-001 and BIOV-121)]
| |
| − | | style="background-color:#91cf61" |Phase II
| |
| − | | style="background-color:#d3d3d3" |
| |
| − | | style="background-color:#d3d3d3" |
| |
| − | |-
| |
| − | |}
| |
| − | ====Chemotherapy====
| |
| − | *[[Clofarabine (Clolar)]] 30 mg/m<sup>2</sup> IV over one hour once per day on days 1 to 5
| |
| − | | |
| − | '''One course'''
| |
| − | ====Subsequent treatment====
| |
| − | *A second induction was permitted for SD or better.
| |
| − | *Faderl et al. 2008: Responders proceeded to clofarabine & cytarabine consolidation
| |
| − | | |
| − | ===References===
| |
| − | # Faderl S, Ravandi F, Huang X, Garcia-Manero G, Ferrajoli A, Estrov Z, Borthakur G, Verstovsek S, Thomas DA, Kwari M, Kantarjian HM. 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. Blood. 2008 Sep 1;112(5):1638-45. Epub 2008 Jun 18. [http://www.bloodjournal.org/content/112/5/1638.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4081352/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/18565853 PubMed]
| |
| − | # Burnett AK, Russell NH, Kell J, Dennis M, Milligan D, Paolini S, Yin J, Culligan D, Johnston P, Murphy J, McMullin MF, Hunter A, Das-Gupta E, Clark R, Carr R, Hills RK. European development of clofarabine as treatment for older patients with acute myeloid leukemia considered unsuitable for intensive chemotherapy. J Clin Oncol. 2010 May 10;28(14):2389-95. Epub 2010 Apr 12. [http://ascopubs.org/doi/full/10.1200/JCO.2009.26.4242 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/20385984 PubMed]
| |
| − | # '''UK NCRI AML16:''' Burnett AK, Russell NH, Hunter AE, Milligan D, Knapper S, Wheatley K, Yin J, McMullin MF, Ali S, Bowen D, Hills RK; UK National Cancer Research Institute AML Working Group. Clofarabine doubles the response rate in older patients with acute myeloid leukemia but does not improve survival. Blood. 2013 Aug 22;122(8):1384-94. Epub 2013 Jul 9. [http://www.bloodjournal.org/content/122/8/1384.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/23838349 PubMed]
| |
| − | | |
| − | ==Clofarabine & LoDAC {{#subobject:7a3edd|Regimen=1}}==
| |
| − | {| class="wikitable" style="float:right; margin-left: 5px;"
| |
| − | |-
| |
| − | |[[#top|back to top]]
| |
| − | |}
| |
| − | Clofarabine & LoDAC: Clofarabine & '''<u>Lo</u>'''w '''<u>D</u>'''ose '''<u>A</u>'''ra-'''<u>C</u>''' (Cytarabine)
| |
| − | ===Variant #1 {{#subobject:12351c|Variant=1}}===
| |
| − | {| class="wikitable" style="width: 100%; text-align:center;"
| |
| − | !Study
| |
| − | ![[Levels_of_Evidence#Evidence|Evidence]]
| |
| − | !Comparator
| |
| − | ![[Levels_of_Evidence#Efficacy|Efficacy]]
| |
| − | |-
| |
| − | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4081352/ Faderl et al. 2008]
| |
| − | | style="background-color:#1a9851" |Randomized Phase II (E)
| |
| − | |[[#Clofarabine_monotherapy|Clofarabine]]
| |
| − | | style="background-color:#91cf60" |Seems to have superior EFS
| |
| − | |-
| |
| − | |}
| |
| − | ====Chemotherapy====
| |
| − | *[[Clofarabine (Clolar)]] 30 mg/m<sup>2</sup> IV over one hour once per day on days 1 to 5, '''given first'''
| |
| − | *[[Cytarabine (Cytosar)]] 20 mg SC once per day on days 1 to 14, '''given 4 hours after clofarabine on days 1 to 5'''
| |
| − | | |
| − | '''One course'''
| |
| − | ====Subsequent treatment====
| |
| − | *A second induction was permitted for SD or better
| |
| − | *Responders proceeded to clofarabine & cytarabine consolidation
| |
| − | | |
| − | ===Variant #2 {{#subobject:7d207f|Variant=1}}===
| |
| − | {| class="wikitable" style="width: 100%; text-align:center;"
| |
| − | !Study
| |
| − | ![[Levels_of_Evidence#Evidence|Evidence]]
| |
| − | |-
| |
| − | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3907176/ Faderl et al. 2010]
| |
| − | | style="background-color:#91cf61" |Phase II
| |
| − | |-
| |
| − | |}
| |
| − | ====Chemotherapy====
| |
| − | *[[Clofarabine (Clolar)]] 20 mg/m<sup>2</sup> IV once per day on days 1 to 5
| |
| − | *[[Cytarabine (Cytosar)]] 20 mg SC BID on days 1 to 10
| |
| − | | |
| − | '''One course'''
| |
| − | ====Subsequent treatment====
| |
| − | *Patients not achieving CR could undergo an identical second induction after at least 28 days.
| |
| − | **Patients not achieving CR after the second induction were given [[#Decitabine_monotherapy_3|salvage decitabine]]
| |
| − | *Patients achieving CR: [[#Clofarabine_.26_LoDAC.2FDecitabine|Clofarabine & low-dose cytarabine alternating with decitabine consolidation]]
| |
| − | | |
| − | ===References===
| |
| − | # Faderl S, Ravandi F, Huang X, Garcia-Manero G, Ferrajoli A, Estrov Z, Borthakur G, Verstovsek S, Thomas DA, Kwari M, Kantarjian HM. 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. Blood. 2008 Sep 1;112(5):1638-45. Epub 2008 Jun 18. [http://www.bloodjournal.org/content/112/5/1638.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4081352/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/18565853 PubMed]
| |
| − | # Faderl S, Ravandi F, Huang X, Wang X, Jabbour E, Garcia-Manero G, Kadia T, Ferrajoli A, Konopleva M, Borthakur G, Burger J, Feliu J, Kantarjian HM. Clofarabine plus low-dose cytarabine followed by clofarabine plus low-dose cytarabine alternating with decitabine in acute myeloid leukemia frontline therapy for older patients. Cancer. 2012 Sep 15;118(18):4471-7. Epub 2012 Jan 26. [https://onlinelibrary.wiley.com/doi/10.1002/cncr.27429/full link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3907176/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/22282348 PubMed]
| |
| − | ## '''Update:''' Kadia TM, Faderl S, Ravandi F, Jabbour E, Garcia-Manero G, Borthakur G, Ferrajoli A, Konopleva M, Burger J, Huang X, Wang X, Pierce S, Brandt M, Feliu J, Cortes J, Kantarjian H. Final results of a phase 2 trial of clofarabine and low-dose cytarabine alternating with decitabine in older patients with newly diagnosed acute myeloid leukemia. Cancer. 2015 Jul 15;121(14):2375-82. Epub 2015 Mar 25. [https://onlinelibrary.wiley.com/doi/10.1002/cncr.29367/full link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5436272/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/25809968 PubMed]
| |
| − | | |
| − | ==CPX-351 monotherapy {{#subobject:03f404|Regimen=1}}==
| |
| − | {| class="wikitable" style="float:right; margin-left: 5px;"
| |
| − | |-
| |
| − | |[[#top|back to top]]
| |
| − | |}
| |
| − | CPX-351: Liposomal Cytarabine and Daunorubicin
| |
| − | ===Regimen {{#subobject:0b4cdf|Variant=1}}===
| |
| − | {| class="wikitable" style="width: 100%; text-align:center;"
| |
| − | !Study
| |
| − | ![[Levels_of_Evidence#Evidence|Evidence]]
| |
| − | !Comparator
| |
| − | ![[Levels_of_Evidence#Efficacy|Efficacy]]
| |
| − | |-
| |
| − | |[http://ascopubs.org/doi/full/10.1200/JCO.2017.77.6112 Lancet et al. 2018 (CLTR0310-301)]
| |
| − | | style="background-color:#1a9851" |Phase III (E)
| |
| − | |[[#7.2B3d_.28intermediate-dose.29|7+3d (intermediate-dose)]]
| |
| − | | style="background-color:#1a9851" |Superior OS
| |
| − | |-
| |
| − | |}
| |
| − | ====Chemotherapy====
| |
| − | *[[Cytarabine and daunorubicin liposomal (Vyxeos)|CPX-351 (Vyxeos)]] as follows:
| |
| − | **First induction: 100 units/m<sup>2</sup> IV over 90 minutes once per day on days 1, 3, 5
| |
| − | **Second induction (if needed): 100 units/m<sup>2</sup> IV over 90 minutes once per day on days 1 & 3
| |
| − | | |
| − | '''One or two courses'''
| |
| − | ====Subsequent treatment====
| |
| − | *CR/CRi: [[#CPX-351_monotherapy_2|CPX-351 monotherapy consolidation]]
| |
| − | | |
| − | ===References===
| |
| − | <!-- # '''Abstract:''' Lancet JE, Uy GL, Cortes JE, Newell LF, Lin TL, Ritchie EK, Stuart RK, Strickland SA, Hogge D, Solomon SR, Stone RM, Bixby DL, Kolitz JE, Schiller GJ, Wieduwilt MJ, Ryan DH, Hoering A, Chiarella M, Louie AC, Medeiros BC. Final results of a phase III randomized trial of CPX-351 versus 7+3 in older patients with newly diagnosed high risk (secondary) AML. J Clin Oncol. 2016 34:15_suppl, 7000-7000 [http://ascopubs.org/doi/abs/10.1200/JCO.2016.34.15_suppl.7000 link to abstract] '''contains partial protocol''' [https://clinicaltrials.gov/ct2/show/NCT01696084 ClinicalTrials.gov] -->
| |
| − | # '''CLTR0310-301:''' Lancet JE, Uy GL, Cortes JE, Newell LF, Lin TL, Ritchie EK, Stuart RK, Strickland SA, Hogge D, Solomon SR, Stone RM, Bixby DL, Kolitz JE, Schiller GJ, Wieduwilt MJ, Ryan DH, Hoering A, Banerjee K, Chiarella M, Louie AC, Medeiros BC. CPX-351 (cytarabine and daunorubicin) liposome for injection versus conventional cytarabine plus daunorubicin in older patients with newly diagnosed secondary acute myeloid leukemia. J Clin Oncol. 2018 Jul 19:JCO2017776112. [Epub ahead of print] [http://ascopubs.org/doi/full/10.1200/JCO.2017.77.6112 link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/300024784 PubMed]
| |
| − | | |
| − | ==Decitabine monotherapy {{#subobject:2d1dad|Regimen=1}}==
| |
| − | {| class="wikitable" style="float:right; margin-left: 5px;"
| |
| − | |-
| |
| − | |[[#top|back to top]]
| |
| − | |}
| |
| − | | |
| − | ===Variant #1 {{#subobject:b60a91|Variant=1}}===
| |
| − | {| class="wikitable" style="width: 100%; text-align:center;"
| |
| − | !Study
| |
| − | ![[Levels_of_Evidence#Evidence|Evidence]]
| |
| − | !Comparator
| |
| − | ![[Levels_of_Evidence#Efficacy|Efficacy]]
| |
| − | |-
| |
| − | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4320000/ Issa et al. 2014]
| |
| − | | style="background-color:#1a9851" |Randomized Phase II (C)
| |
| − | |[[#Decitabine_.26_Valproate|Decitabine & Valproate]]
| |
| − | | style="background-color:#ffffbf" |Seems not superior
| |
| − | |-
| |
| − | |}
| |
| − | ====Chemotherapy====
| |
| − | *[[Decitabine (Dacogen)]] 20 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1 to 5
| |
| − | | |
| − | '''4- to 6-week cycles'''
| |
| − | | |
| − | ===Variant #2 {{#subobject:22a24e|Variant=1}}===
| |
| − | {| class="wikitable" style="width: 100%; text-align:center;"
| |
| − | !Study
| |
| − | ![[Levels_of_Evidence#Evidence|Evidence]]
| |
| − | !Comparator
| |
| − | ![[Levels_of_Evidence#Efficacy|Efficacy]]
| |
| − | |-
| |
| − | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4874148/ Kantarjian et al. 2012]
| |
| − | | style="background-color:#1a9851" |Phase III (E)
| |
| − | |[[#LoDAC|LoDAC]]<br> [[#Best_supportive_care|Best supportive care]]
| |
| − | | style="background-color:#d9ef8b" |Might have superior OS
| |
| − | |-
| |
| − | |}
| |
| − | ====Chemotherapy====
| |
| − | *[[Decitabine (Dacogen)]] 20 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1 to 5
| |
| − | *[[Hydroxyurea (Hydrea)]] could be used up until cycle 1 day 15
| |
| − | | |
| − | '''28-day cycles'''
| |
| − | | |
| − | ===Variant #3 {{#subobject:c6ffdd|Variant=1}}===
| |
| − | {| class="wikitable" style="width: 100%; text-align:center;"
| |
| − | !Study
| |
| − | ![[Levels_of_Evidence#Evidence|Evidence]]
| |
| − | |-
| |
| − | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2867720/ Blum et al. 2010]
| |
| − | | style="background-color:#91cf61" |Phase II
| |
| − | |-
| |
| − | |[https://www.nejm.org/doi/full/10.1056/NEJMoa1605949 Welch et al. 2016]
| |
| − | | style="background-color:#91cf61" |Phase II
| |
| − | |-
| |
| − | |}
| |
| − | ====Chemotherapy====
| |
| − | *[[Decitabine (Dacogen)]] 20 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1 to 10
| |
| − | *[[Hydroxyurea (Hydrea)]] allowed during and prior to cycle 1
| |
| − | | |
| − | '''28-day cycles'''
| |
| − | | |
| − | ''Additional therapy depending on response in Blum et al.:''
| |
| − | *''Patients with persistent AML (greater than or equal to 5% blasts) received repeated cycles with 10 days of decitabine as described above.''
| |
| − | *''Patients with no morphologic evidence of AML (less than 5% blasts) received 5 days of decitabine as described by [[#Decitabine_monotherapy_maintenance|decitabine monotherapy maintenance]].''
| |
| − | | |
| − | ===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. Epub 2010 Apr 5. [http://www.pnas.org/content/107/16/7473.full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2867720/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/20368434 PubMed]
| |
| − | <!-- Presented in part at the 47th Annual Meeting of the American Society of Clinical Oncology, Chicago, IL, June 3-7, 2011. -->
| |
| − | # Kantarjian HM, Thomas XG, Dmoszyńska 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. Epub 2012 Jun 11. [http://jco.ascopubs.org/content/30/21/2670.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4874148/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/22689805 PubMed]
| |
| − | # Issa JP, Garcia-Manero G, Huang X, Cortes J, Ravandi F, Jabbour E, Borthakur G, Brandt M, Pierce S, Kantarjian HM. Results of phase 2 randomized study of low-dose decitabine with or without valproic acid in patients with myelodysplastic syndrome and acute myelogenous leukemia. Cancer. 2015 Feb 15;121(4):556-61. Epub 2014 Oct 21. [https://onlinelibrary.wiley.com/doi/10.1002/cncr.29085/full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4320000/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/25336333 PubMed]
| |
| − | # Welch JS, Petti AA, Miller CA, Fronick CC, O'Laughlin M, Fulton RS, Wilson RK, Baty JD, Duncavage EJ, Tandon D, Lee Y, Wartman LD, Uy GL, Ghobadi A, Tomasson MH, Pusic I, Romee R, Fehniger TA, Stockerl-Goldstein KE, Vij R, Oh ST, Abboud CN, Cashen AF, Schroeder MA, Jacoby MA, Heath SE, Luber K, Janke MR, Hantel A, Khan N, Sukhanova MJ, Knoebel RW, Stock W, Graubert TA, Walter MJ, Westervelt P, Link DC, DiPersio JF, Ley TJ. TP53 and decitabine in acute myeloid leukemia and myelodysplastic syndromes. N Engl J Med. 2016 Nov 24;375(21):2023-2036. [https://www.nejm.org/doi/full/10.1056/NEJMoa1605949#article_supplementary_material link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5217532/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/27959731 PubMed]
| |
| − | | |
| − | ==Decitabine & Valproate {{#subobject:948b49|Regimen=1}}==
| |
| − | {| class="wikitable" style="float:right; margin-left: 5px;"
| |
| − | |-
| |
| − | |[[#top|back to top]]
| |
| − | |}
| |
| − | | |
| − | ===Regimen {{#subobject:c7b35a|Variant=1}}===
| |
| − | {| class="wikitable" style="width: 100%; text-align:center;"
| |
| − | !Study
| |
| − | ![[Levels_of_Evidence#Evidence|Evidence]]
| |
| − | !Comparator
| |
| − | ![[Levels_of_Evidence#Efficacy|Efficacy]]
| |
| − | |-
| |
| − | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1895437/ Garcia-Manero et al. 2006]
| |
| − | | style="background-color:#91cf61" |Phase II
| |
| − | | style="background-color:#d3d3d3" |
| |
| − | | style="background-color:#d3d3d3" |
| |
| − | |-
| |
| − | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4320000/ Issa et al. 2014]
| |
| − | | style="background-color:#1a9851" |Randomized Phase II (E)
| |
| − | |[[#Decitabine_monotherapy|Decitabine]]
| |
| − | | style="background-color:#ffffbf" |Seems not superior
| |
| − | |-
| |
| − | |}
| |
| − | ====Chemotherapy====
| |
| − | *[[Decitabine (Dacogen)]] 15 mg/m<sup>2</sup> IV over 60 minutes once per day 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 cycle for 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. [http://www.bloodjournal.org/content/108/10/3271.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1895437/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/16882711 PubMed]
| |
| − | # Issa JP, Garcia-Manero G, Huang X, Cortes J, Ravandi F, Jabbour E, Borthakur G, Brandt M, Pierce S, Kantarjian HM. Results of phase 2 randomized study of low-dose decitabine with or without valproic acid in patients with myelodysplastic syndrome and acute myelogenous leukemia. Cancer. 2015 Feb 15;121(4):556-61. Epub 2014 Oct 21. [https://onlinelibrary.wiley.com/doi/10.1002/cncr.29085/full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4320000/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/25336333 PubMed]
| |
| − | | |
| − | ==ICL {{#subobject:a904d7|Regimen=1}}==
| |
| − | {| class="wikitable" style="float:right; margin-left: 5px;"
| |
| − | |-
| |
| − | |[[#top|back to top]]
| |
| − | |}
| |
| − | ICL: '''<u>I</u>'''darubicin, '''<u>C</u>'''ytarabine, '''<u>L</u>'''omustine
| |
| − | ===Regimen {{#subobject:909d7e|Variant=1}}===
| |
| − | {| class="wikitable" style="width: 100%; text-align:center;"
| |
| − | !Study
| |
| − | ![[Levels_of_Evidence#Evidence|Evidence]]
| |
| − | |-
| |
| − | |[http://ascopubs.org/doi/full/10.1200/JCO.2016.67.6213 Pigneux et al. 2016 (GOELAMS LAM-SA2002)]
| |
| − | | style="background-color:#91cf61" |Non-randomized portion of RCT
| |
| − | |-
| |
| − | |}
| |
| − | ====Chemotherapy====
| |
| − | *[[Idarubicin (Idamycin)]] 8 mg/m<sup>2</sup> IV once per day on days 1 to 5
| |
| − | *[[Cytarabine (Cytosar)]] 100 mg/m<sup>2</sup>/day IV continuous infusion on days 1 to 7
| |
| − | *[[Lomustine (Ceenu)]] 200 mg/m<sup>2</sup> PO once on day 1
| |
| − | | |
| − | '''One course'''
| |
| − | | |
| − | ''See paper for further details about post-induction therapy''
| |
| − | | |
| − | ===References===
| |
| − | # Pigneux A, Béné MC, Guardiola P, Recher C, Hamel JF, Sauvezie M, Harousseau JL, Tournilhac O, Witz F, Berthou C, Escoffre-Barbe M, Guyotat D, Fegueux N, Himberlin C, Hunault M, Delain M, Lioure B, Jourdan E, Bauduer F, Dreyfus F, Cahn JY, Sotto JJ, Ifrah N. Addition of Androgens Improves Survival in Elderly Patients With Acute Myeloid Leukemia: A GOELAMS Study. J Clin Oncol. 2017 Feb;35(4):387-393. Epub 2016 Oct 24. [http://ascopubs.org/doi/full/10.1200/JCO.2016.67.6213 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/28129526 PubMed]
| |
| − | | |
| − | ==LoDAC {{#subobject:25e1c6|Regimen=1}}==
| |
| − | {| class="wikitable" style="float:right; margin-left: 5px;"
| |
| − | |-
| |
| − | |[[#top|back to top]]
| |
| − | |}
| |
| − | LoDAC: '''<u>Lo</u>'''w '''<u>D</u>'''ose '''<u>A</u>'''ra-'''<u>C</u>''' (Cytarabine)
| |
| − | <br>LDAC: '''<u>L</u>'''ow-dose '''<u>A</u>'''ra-'''<u>C</u>''' (Cytarabine)
| |
| − | | |
| − | ===Variant #1, limited duration {{#subobject:d5c6f7|Variant=1}}===
| |
| − | {| class="wikitable" style="width: 100%; text-align:center;"
| |
| − | !Study
| |
| − | ![[Levels_of_Evidence#Evidence|Evidence]]
| |
| − | !Comparator
| |
| − | ![[Levels_of_Evidence#Efficacy|Efficacy]]
| |
| − | |-
| |
| − | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3533673/ Sekeres et al. 2012]
| |
| − | | style="background-color:#1a9851" |Randomized Phase II (C)
| |
| − | |LDAC & Lintuzumab
| |
| − | | style="background-color:#ffffbf" |Seems not superior
| |
| − | |-
| |
| − | |[http://www.bloodjournal.org/content/122/8/1384.long Burnett et al. 2013 (UK NCRI AML16)]
| |
| − | | style="background-color:#1a9851" |Phase III (C)
| |
| − | |[[#Clofarabine_monotherapy|Clofarabine]]
| |
| − | | style="background-color:#ffffbf" |Seems not superior
| |
| − | |-
| |
| − | | rowspan="2" |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4536889/ Dennis et al. 2015]
| |
| − | | rowspan="2" style="background-color:#1a9851" |Randomized (C)
| |
| − | |LDAC & Vosaroxin
| |
| − | | style="background-color:#ffffbf" |Seems not superior
| |
| − | |-
| |
| − | |Vosaroxin
| |
| − | | style="background-color:#ffffbf" |Seems not superior
| |
| − | |-
| |
| − | |[https://www.nature.com/leu/journal/v29/n6/full/leu201538a.html Burnett et al. 2015]
| |
| − | | style="background-color:#1a9851" |Randomized (C)
| |
| − | |Sapacitabine
| |
| − | | style="background-color:#fee08b" |Might have inferior CR rate
| |
| − | |-
| |
| − | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4504945/ Dombret et al. 2015 (AZA-AML-001)]
| |
| − | | style="background-color:#1a9851" |Phase III (C)
| |
| − | |[[#Azacitidine_monotherapy|Azacitidine]]
| |
| − | | style="background-color:#fee08b" |Might have inferior OS
| |
| − | |-
| |
| − | |}
| |
| − | ====Chemotherapy====
| |
| − | *[[Cytarabine (Cytosar)]] 20 mg/m<sup>2</sup> SC BID on days 1 to 10
| |
| − | | |
| − | '''4- to 6-week cycle for up to 4 cycles'''
| |
| − | | |
| − | ===Variant #2, indefinite duration {{#subobject:fd61d0|Variant=1}}===
| |
| − | {| class="wikitable" style="width: 100%; text-align:center;"
| |
| − | !Study
| |
| − | ![[Levels_of_Evidence#Evidence|Evidence]]
| |
| − | !Comparator
| |
| − | ![[Levels_of_Evidence#Efficacy|Efficacy]]
| |
| − | |-
| |
| − | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4874148/ Kantarjian et al. 2012]
| |
| − | | style="background-color:#1a9851" |Phase III (C)
| |
| − | |[[#Decitabine_monotherapy|Decitabine]]
| |
| − | | style="background-color:#fee08b" |Might have inferior OS
| |
| − | |-
| |
| − | |}
| |
| − | ====Chemotherapy====
| |
| − | *[[Cytarabine (Cytosar)]] 20 mg/m<sup>2</sup> SC once per day on days 1 to 10
| |
| − | | |
| − | '''28-day cycles until progression or intolerance'''
| |
| − | | |
| − | ===References===
| |
| − | <!-- Presented in part at the 47th Annual Meeting of the American Society of Clinical Oncology, Chicago, IL, June 3-7, 2011. -->
| |
| − | # Kantarjian HM, Thomas XG, Dmoszyńska 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. Epub 2012 Jun 11. [http://jco.ascopubs.org/content/30/21/2670.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4874148/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/22689805 PubMed]
| |
| − | # Sekeres MA, Lancet JE, Wood BL, Grove LE, Sandalic L, Sievers EL, Jurcic JG. Randomized phase IIb study of low-dose cytarabine and lintuzumab versus low-dose cytarabine and placebo in older adults with untreated acute myeloid leukemia. Haematologica. 2013 Jan;98(1):119-28. Epub 2012 Jul 16. [http://www.haematologica.org/content/98/1/119.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3533673/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/22801961 PubMed]
| |
| − | # '''UK NCRI AML16:''' Burnett AK, Russell NH, Hunter AE, Milligan D, Knapper S, Wheatley K, Yin J, McMullin MF, Ali S, Bowen D, Hills RK; UK National Cancer Research Institute AML Working Group. Clofarabine doubles the response rate in older patients with acute myeloid leukemia but does not improve survival. Blood. 2013 Aug 22;122(8):1384-94. Epub 2013 Jul 9. [http://www.bloodjournal.org/content/122/8/1384.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/23838349 PubMed]
| |
| − | # Dennis M, Russell N, Hills RK, Hemmaway C, Panoskaltsis N, McMullin MF, Kjeldsen L, Dignum H, Thomas IF, Clark RE, Milligan D, Burnett AK. Vosaroxin and vosaroxin plus low-dose Ara-C (LDAC) vs low-dose Ara-C alone in older patients with acute myeloid leukemia. Blood. 2015 May 7;125(19):2923-32. Epub 2015 Mar 24. [http://www.bloodjournal.org/content/125/19/2923.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4536889/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/25805811 PubMed]
| |
| − | # Burnett AK, Russell N, Hills RK, Panoskaltsis N, Khwaja A, Hemmaway C, Cahalin P, Clark RE, Milligan D. A randomised comparison of the novel nucleoside analogue sapacitabine with low-dose cytarabine in older patients with acute myeloid leukaemia. Leukemia. 2015 Jun;29(6):1312-9. Epub 2015 Feb 13. [https://www.nature.com/leu/journal/v29/n6/full/leu201538a.html link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/25676423 PubMed]
| |
| − | # '''AZA-AML-001:''' Dombret H, Seymour JF, Butrym A, Wierzbowska A, Selleslag D, Jang JH, Kumar R, Cavenagh J, Schuh AC, Candoni A, Récher C, Sandhu I, Bernal Del Castillo T, Al-Ali HK, Martinelli G, Falantes J, Noppeney R, Stone RM, Minden MD, McIntyre H, Songer S, Lucy LM, Beach CL, Döhner H. International phase 3 study of azacitidine vs conventional care regimens in older patients with newly diagnosed AML with >30% blasts. Blood. 2015 Jul 16;126(3):291-9. Epub 2015 May 18. [http://www.bloodjournal.org/content/126/3/291.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4504945/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/25987659 PubMed]
| |
| − | ## '''Subgroup analysis:''' Seymour JF, Döhner H, Butrym A, Wierzbowska A, Selleslag D, Jang JH, Kumar R, Cavenagh J, Schuh AC, Candoni A, Récher C, Sandhu I, Del Castillo TB, Al-Ali HK, Falantes J, Stone RM, Minden MD, Weaver J, Songer S, Beach CL, Dombret H. Azacitidine improves clinical outcomes in older patients with acute myeloid leukaemia with myelodysplasia-related changes compared with conventional care regimens. BMC Cancer. 2017 Dec 14;17(1):852. [https://bmccancer.biomedcentral.com/articles/10.1186/s12885-017-3803-6 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5731212/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/29241450 PubMed]
| |
| − | | |
| − | ==Temozolomide monotherapy {{#subobject:261bcb|Regimen=1}}==
| |
| − | {| class="wikitable" style="float:right; margin-left: 5px;"
| |
| − | |-
| |
| − | |[[#top|back to top]]
| |
| − | |}
| |
| − | | |
| − | ===Regimen {{#subobject:fb4aeb|Variant=1}}===
| |
| − | {| class="wikitable" style="width: 100%; text-align:center;"
| |
| − | !Study
| |
| − | ![[Levels_of_Evidence#Evidence|Evidence]]
| |
| − | |-
| |
| − | |[https://onlinelibrary.wiley.com/doi/10.1111/bjh.13094/full Brandwein et al. 2014]
| |
| − | | style="background-color:#91cf61" |Phase II
| |
| − | |-
| |
| − | |}
| |
| − | | |
| − | ''Patient selection was based on MGMT expression by Western blot. See article for details.''
| |
| − | ====Chemotherapy====
| |
| − | *[[Temozolomide (Temodar)]] 200 mg/m<sup>2</sup>/day PO on days 1 to 7; complete responders could receive 200 mg/m<sup>2</sup>/day PO on days 1 to 5
| |
| − | | |
| − | '''28-day cycle for up to 12 cycles'''
| |
| − | | |
| − | ===References===
| |
| − | # Brandwein JM, Kassis J, Leber B, Hogge D, Howson-Jan K, Minden MD, Galarneau A, Pouliot JF. Phase II study of targeted therapy with temozolomide in acute myeloid leukaemia and high-risk myelodysplastic syndrome patients pre-screened for low O(6) -methylguanine DNA methyltransferase expression. Br J Haematol. 2014 Dec;167(5):664-70. Epub 2014 Aug 27. [https://onlinelibrary.wiley.com/doi/10.1111/bjh.13094/full link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/25160658 PubMed]
| |
| | | | |
| | =Consolidation after upfront therapy= | | =Consolidation after upfront therapy= |
| − | ==5+2d {{#subobject:b409f7|Regimen=1}}== | + | ==HiDAC & Midostaurin {{#subobject:a12f1b|Regimen=1}}== |
| − | {| class="wikitable" style="float:right; margin-left: 5px;"
| + | {{#subobject:c3e162|Variant=1}} |
| − | |-
| + | {{:Cytarabine & Midostaurin consolidation therapy for acute myeloid leukemia (AML)}} |
| − | |[[#top|back to top]]
| |
| − | |}
| |
| − | ===Regimen {{#subobject:a67da7|Variant=1}}===
| |
| − | {| class="wikitable" style="width: 100%; text-align:center;" | |
| − | !Study
| |
| − | ![[Levels_of_Evidence#Evidence|Evidence]]
| |
| − | |-
| |
| − | |[http://ascopubs.org/doi/abs/10.1200/JCO.2016.34.15_suppl.7000 Lancet et al. 2016 (CLTR0310-301)]
| |
| − | | style="background-color:#91cf61" |Non-randomized portion of RCT
| |
| − | |-
| |
| − | |}
| |
| − | ====Preceding treatment====
| |
| − | *[[#7.2B3d_.28intermediate-dose.29|7+3d (intermediate-dose)]]
| |
| − | | |
| − | ====Chemotherapy====
| |
| − | *[[Cytarabine (Cytosar)]] 100 mg/m<sup>2</sup>/day IV continuous infusion on days 1 to 5 (total dose: 500 mg/m<sup>2</sup>)
| |
| − | *[[Daunorubicin (Cerubidine)]] 60 mg/m<sup>2</sup> IV once per day on days 1 & 2
| |
| − | | |
| − | '''5-day course'''
| |
| | | | |
| − | ===References=== | + | ==IDAC & Sorafenib {{#subobject:c2cc06|Regimen=1}}== |
| − | # '''Abstract:''' Lancet JE, Uy GL, Cortes JE, Newell LF, Lin TL, Ritchie EK, Stuart RK, Strickland SA, Hogge D, Solomon SR, Stone RM, Bixby DL, Kolitz JE, Schiller GJ, Wieduwilt MJ, Ryan DH, Hoering A, Chiarella M, Louie AC, Medeiros BC. Final results of a phase III randomized trial of CPX-351 versus 7+3 in older patients with newly diagnosed high risk (secondary) AML. J Clin Oncol. 2016 34:15_suppl, 7000-7000 [http://ascopubs.org/doi/abs/10.1200/JCO.2016.34.15_suppl.7000 link to abstract] '''contains partial protocol''' [https://clinicaltrials.gov/ct2/show/NCT01696084 ClinicalTrials.gov] | |
| − | | |
| − | ==Allogeneic hematopoietic stem cell transplant==
| |
| | {| class="wikitable" style="float:right; margin-left: 5px;" | | {| class="wikitable" style="float:right; margin-left: 5px;" |
| | |- | | |- |
| | |[[#top|back to top]] | | |[[#top|back to top]] |
| | |} | | |} |
| − | To be completed.
| + | IDAC & Sorafenib: '''<u>I</u>'''ntermediate '''<u>D</u>'''ose '''<u>A</u>'''ra-'''<u>C</u>''' (Cytarabine) & Sorafenib |
| − | | + | ===Regimen {{#subobject:b52969|Variant=1}}=== |
| − | ==Autologous hematopoietic stem cell transplant==
| |
| − | {| class="wikitable" style="float:right; margin-left: 5px;"
| |
| − | |-
| |
| − | |[[#top|back to top]]
| |
| − | |}
| |
| − | Not frequently used in the United States but has some role in good-risk patients. To be completed.
| |
| − | | |
| − | ==Azacitidine monotherapy {{#subobject:7abfd6|Regimen=1}}==
| |
| − | {| class="wikitable" style="float:right; margin-left: 5px;"
| |
| − | |-
| |
| − | |[[#top|back to top]]
| |
| − | |}
| |
| − | ===Regimen {{#subobject:f7e3f6|Variant=1}}=== | |
| | {| class="wikitable" style="width: 100%; text-align:center;" | | {| class="wikitable" style="width: 100%; text-align:center;" |
| | !Study | | !Study |
| | ![[Levels_of_Evidence#Evidence|Evidence]] | | ![[Levels_of_Evidence#Evidence|Evidence]] |
| | |- | | |- |
| − | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3829116/ Nand et al. 2013 (SWOG S0703)] | + | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5637402/ Uy et al. 2017 (CALGB 11001)] |
| | | style="background-color:#91cf61" |Phase II | | | style="background-color:#91cf61" |Phase II |
| | |- | | |- |
| | |} | | |} |
| | ====Preceding treatment==== | | ====Preceding treatment==== |
| − | *[[#Azacitidine_.26_Gemtuzumab_ozogamicin_2|Azacitidine & Gemtuzumab ozogamicin consolidation]] | + | *[[#7.2B3d_.26_Sorafenib|7+3d & sorafenib induction]] |
| | ====Chemotherapy==== | | ====Chemotherapy==== |
| − | *[[Azacitidine (Vidaza)]] 75 mg/m<sup>2</sup> SC once on day 1 | + | *[[Cytarabine (Cytosar)]] 2000 mg/m<sup>2</sup> IV over 3 hours once per day on days 1 to 5 |
| | + | *[[Sorafenib (Nexavar)]] 400 mg PO BID for 28 days |
| | | | |
| − | '''28-day cycle for 4 cycles''' | + | '''Two cycles''' |
| − | | |
| − | ===References===
| |
| − | <!-- Presented in part at the American Society of Clinical Oncology annual meeting (Chicago, IL, June 1-5, 2012) and at the American Society of Hematology annual meeting (Atlanta, GA, December 8-11, 2012). -->
| |
| − | # '''SWOG S0703:''' Nand S, Othus M, Godwin JE, Willman CL, Norwood TH, Howard DS, Coutre SE, Erba HP, Appelbaum FR. A phase 2 trial of azacitidine and gemtuzumab ozogamicin therapy in older patients with acute myeloid leukemia. Blood. 2013 Nov 14;122(20):3432-9. Epub 2013 Oct 3. [http://www.bloodjournal.org/content/122/20/3432.full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3829116/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/24092933 PubMed]
| |
| − | | |
| − | ==Azacitidine & Gemtuzumab ozogamicin {{#subobject:e5ff95|Regimen=1}}==
| |
| − | {| class="wikitable" style="float:right; margin-left: 5px;"
| |
| − | |-
| |
| − | |[[#top|back to top]]
| |
| − | |}
| |
| − | ===Regimen {{#subobject:eb3f69|Variant=1}}===
| |
| − | {| class="wikitable" style="width: 100%; text-align:center;"
| |
| − | !Study
| |
| − | ![[Levels_of_Evidence#Evidence|Evidence]]
| |
| − | |-
| |
| − | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3829116/ Nand et al. 2013 (SWOG S0703)]
| |
| − | | style="background-color:#91cf61" |Phase II
| |
| − | |-
| |
| − | |}
| |
| − | ====Preceding treatment====
| |
| − | *[[#Azacitidine_.26_Gemtuzumab_ozogamicin|Azacitidine & Gemtuzumab ozogamicin induction]]
| |
| − | ====Chemotherapy====
| |
| − | *[[Azacitidine (Vidaza)]] 75 mg/m<sup>2</sup> SC or IV once per day on days 1 to 7
| |
| − | *[[Gemtuzumab ozogamicin (Mylotarg)]] 3 mg/m<sup>2</sup> IV once on day 8
| |
| − | | |
| − | ====Supportive medications====
| |
| − | *"Appropriate premedications" which were not specified, for [[Gemtuzumab ozogamicin (Mylotarg)]]
| |
| − | *Growth factors per physician discretion
| |
| − | | |
| − | '''1 cycle'''
| |
| − | ====Subsequent treatment====
| |
| − | *[[#Azacitidine_monotherapy_2|Azacitidine maintenance]], within 42 days of completion of consolidation
| |
| − | | |
| − | ===References===
| |
| − | <!-- Presented in part at the American Society of Clinical Oncology annual meeting (Chicago, IL, June 1-5, 2012) and at the American Society of Hematology annual meeting (Atlanta, GA, December 8-11, 2012). -->
| |
| − | # '''SWOG S0703:''' Nand S, Othus M, Godwin JE, Willman CL, Norwood TH, Howard DS, Coutre SE, Erba HP, Appelbaum FR. A phase 2 trial of azacitidine and gemtuzumab ozogamicin therapy in older patients with acute myeloid leukemia. Blood. 2013 Nov 14;122(20):3432-9. Epub 2013 Oct 3. [http://www.bloodjournal.org/content/122/20/3432.full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3829116/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/24092933 PubMed]
| |
| − | | |
| − | ==Busulfan & Cyclophosphamide, then auto HSCT {{#subobject:9acbe9|Regimen=1}}==
| |
| − | {| class="wikitable" style="float:right; margin-left: 5px;"
| |
| − | |-
| |
| − | |[[#top|back to top]]
| |
| − | |}
| |
| − | ===Regimen {{#subobject:6ccf66|Variant=1}}===
| |
| − | {| class="wikitable" style="width: 100%; text-align:center;"
| |
| − | !Study
| |
| − | ![[Levels_of_Evidence#Evidence|Evidence]]
| |
| − | !Comparator
| |
| − | ![[Levels_of_Evidence#Efficacy|Efficacy]]
| |
| − | |-
| |
| − | |[http://www.bloodjournal.org/content/118/23/6037.long Vellenga et al. 2011 (HOVON-SAKK AML-29/AML-42)]
| |
| − | | style="background-color:#1a9851" |Phase III (E)
| |
| − | |[[#Etoposide_.26_Mitoxantrone|Etoposide & Mitoxantrone]]
| |
| − | | style="background-color:#d9ef8b" |Might have superior RFS
| |
| − | |-
| |
| − | |}
| |
| − | ====Preceding treatment====
| |
| − | *[[#7.2B3i|7+3i]], then amsacrine & cytarabine
| |
| − | {{#lst:Autologous HSCT|6ccf66}}
| |
| − | ===References===
| |
| − | # '''HOVON-SAKK AML-29/AML-42:''' Vellenga E, van Putten W, Ossenkoppele GJ, Verdonck LF, Theobald M, Cornelissen JJ, Huijgens PC, Maertens J, Gratwohl A, Schaafsma R, Schanz U, Graux C, Schouten HC, Ferrant A, Bargetzi M, Fey MF, Löwenberg B; Dutch-Belgian Hemato-Oncology Cooperative Group (HOVON); Swiss Group for Clinical Cancer Research Collaborative Group (SAKK). Autologous peripheral blood stem cell transplantation for acute myeloid leukemia. Blood. 2011 Dec 1;118(23):6037-42. Epub 2011 Sep 27. [http://www.bloodjournal.org/content/118/23/6037.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/21951683 PubMed]
| |
| − | | |
| − | ==CIA {{#subobject:db5c09|Regimen=1}}==
| |
| − | {| class="wikitable" style="float:right; margin-left: 5px;"
| |
| − | |-
| |
| − | |[[#top|back to top]]
| |
| − | |}
| |
| − | CIA: '''<u>C</u>'''lofarabine, '''<u>I</u>'''darubicin, '''<u>A</u>'''ra-C (Cytarabine)
| |
| − | ===Regimen {{#subobject:1bbed8|Variant=1}}===
| |
| − | {| class="wikitable" style="width: 100%; text-align:center;"
| |
| − | !Study
| |
| − | ![[Levels_of_Evidence#Evidence|Evidence]]
| |
| − | |-
| |
| − | |[https://onlinelibrary.wiley.com/doi/10.1002/ajh.23544/references Nazha et al. 2013]
| |
| − | | style="background-color:#91cf61" |Phase II
| |
| − | |-
| |
| − | |}
| |
| − | ====Preceding treatment====
| |
| − | *[[#CIA|CIA induction]]
| |
| − | ====Chemotherapy====
| |
| − | *[[Clofarabine (Clolar)]] 15 mg/m<sup>2</sup> IV once per day on days 1 to 3
| |
| − | *[[Idarubicin (Idamycin)]] 8 mg/m<sup>2</sup> IV once per day on days 1 & 2
| |
| − | *[[Cytarabine (Cytosar)]] 750 mg/m<sup>2</sup> IV once per day on days 1 to 3
| |
| − | | |
| − | '''3-day course; repeated every 3 to 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. Epub 2013 Sep 9. [https://onlinelibrary.wiley.com/doi/10.1002/ajh.23544/references long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4110914/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/23877926 PubMed]
| |
| − | | |
| − | ==CLARA {{#subobject:6160cf|Regimen=1}}==
| |
| − | {| class="wikitable" style="float:right; margin-left: 5px;"
| |
| − | |-
| |
| − | |[[#top|back to top]]
| |
| − | |}
| |
| − | CLARA: '''<u>CL</u>'''ofarabine and '''<u>ARA</u>'''-C (Cytarabine)
| |
| − | ===Regimen {{#subobject:6ed739|Variant=1}}===
| |
| − | {| class="wikitable" style="width: 100%; text-align:center;"
| |
| − | !Study
| |
| − | ![[Levels_of_Evidence#Evidence|Evidence]]
| |
| − | !Comparator
| |
| − | ![[Levels_of_Evidence#Efficacy|Efficacy]]
| |
| − | |-
| |
| − | |[http://ascopubs.org/doi/full/10.1200/JCO.2016.70.4551 Thomas et al. 2017 (ALFA-0702)]
| |
| − | | style="background-color:#1a9851" |Randomized Phase II (E)
| |
| − | |[[#HDAC_.26_G-CSF|HDAC & G-CSF]]
| |
| − | | style="background-color:#91cf60" |Seems to have superior RFS
| |
| − | |-
| |
| − | |}
| |
| − | ====Preceding treatment====
| |
| − | *Cytarabine, Daunorubicin, G-CSF induction
| |
| − | ====Chemotherapy====
| |
| − | *[[Clofarabine (Clolar)]] 30 mg/m<sup>2</sup> IV over 2 hours once per day on days 2 to 6, '''given first'''
| |
| − | *[[Cytarabine (Cytosar)]] 1000 mg/m<sup>2</sup> IV over 2 hours once per day on days 1 to 5, '''given second, 4 hours after clofarabine, on days 2 to 5'''
| |
| − | *[[Filgrastim (Neupogen)]] 5 mcg/kg IV once per day on days 1 to 6
| |
| − | | |
| − | '''35-day cycle for 3 cycles'''
| |
| − | | |
| − | ===References===
| |
| − | # '''ALFA-0702:''' Thomas X, de Botton S, Chevret S, Caillot D, Raffoux E, Lemasle E, Marolleau JP, Berthon C, Pigneux A, Vey N, Reman O, Simon M, Recher C, Cahn JY, Hermine O, Castaigne S, Celli-Lebras K, Ifrah N, Preudhomme C, Terré C, Dombret H. Randomized phase II study of clofarabine-based consolidation for younger adults with acute myeloid leukemia in first remission. J Clin Oncol. 2017 Apr 10;35(11):1223-1230. Epub 2017 Feb 21. [http://ascopubs.org/doi/full/10.1200/JCO.2016.70.4551 link to original article] '''contains verified protocol in supplement''' [https://www.ncbi.nlm.nih.gov/pubmed/28221862 PubMed]
| |
| − | | |
| − | ==Clofarabine & LoDAC/Decitabine {{#subobject:756e06|Regimen=1}}==
| |
| − | {| class="wikitable" style="float:right; margin-left: 5px;"
| |
| − | |-
| |
| − | |[[#top|back to top]]
| |
| − | |}
| |
| − | Clofarabine & LoDAC/Decitabine: Clofarabine & '''<u>Lo</u>'''w '''<u>D</u>'''ose '''<u>A</u>'''ra-'''<u>C</u>''' (Cytarabine) alternating with Decitabine
| |
| − | ===Regimen {{#subobject:0ac883|Variant=1}}===
| |
| − | {| class="wikitable" style="width: 100%; text-align:center;"
| |
| − | !Study
| |
| − | ![[Levels_of_Evidence#Evidence|Evidence]]
| |
| − | |-
| |
| − | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3907176/ Faderl et al. 2010]
| |
| − | | style="background-color:#91cf61" |Phase II
| |
| − | |-
| |
| − | |}
| |
| − | ====Preceding treatment====
| |
| − | *[[#Clofarabine_.26_LoDAC|Clofarabine & LoDAC]], which is counted as "Cycle 1". Cycles are given every 4 to 7 weeks pending hematologic recovery and resolution of other toxicities.
| |
| − | | |
| − | ====Chemotherapy, clofarabine & LoDAC portion====
| |
| − | *[[Clofarabine (Clolar)]] 20 mg/m<sup>2</sup> IV once per day on days 1 to 3
| |
| − | *[[Cytarabine (Cytosar)]] 20 mg SC BID on days 1 to 7
| |
| − | | |
| − | '''Cycles 2, 3, 7 to 9, 13 to 15'''
| |
| − | | |
| − | ====Chemotherapy, decitabine portion====
| |
| − | *[[Decitabine (Dacogen)]] 20 mg/m<sup>2</sup> IV once per day on days 1 to 5
| |
| − | | |
| − | '''Cycles 4 to 6, 10 to 12, 16 to 18'''
| |
| − | | |
| − | ===References===
| |
| − | # Faderl S, Ravandi F, Huang X, Wang X, Jabbour E, Garcia-Manero G, Kadia T, Ferrajoli A, Konopleva M, Borthakur G, Burger J, Feliu J, Kantarjian HM. Clofarabine plus low-dose cytarabine followed by clofarabine plus low-dose cytarabine alternating with decitabine in acute myeloid leukemia frontline therapy for older patients. Cancer. 2012 Sep 15;118(18):4471-7. Epub 2012 Jan 26. [https://onlinelibrary.wiley.com/doi/10.1002/cncr.27429/full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3907176/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/22282348 PubMed]
| |
| − | ## '''Update:''' Kadia TM, Faderl S, Ravandi F, Jabbour E, Garcia-Manero G, Borthakur G, Ferrajoli A, Konopleva M, Burger J, Huang X, Wang X, Pierce S, Brandt M, Feliu J, Cortes J, Kantarjian H. Final results of a phase 2 trial of clofarabine and low-dose cytarabine alternating with decitabine in older patients with newly diagnosed acute myeloid leukemia. Cancer. 2015 Jul 15;121(14):2375-82. Epub 2015 Mar 25. [https://onlinelibrary.wiley.com/doi/10.1002/cncr.29367/full link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5436272/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/25809968 PubMed]
| |
| − | | |
| − | ==CPX-351 monotherapy {{#subobject:6a5fb5|Regimen=1}}==
| |
| − | {| class="wikitable" style="float:right; margin-left: 5px;"
| |
| − | |-
| |
| − | |[[#top|back to top]]
| |
| − | |}
| |
| − | CPX-351: Liposomal Cytarabine and Daunorubicin
| |
| − | ===Regimen {{#subobject:896083|Variant=1}}===
| |
| − | {| class="wikitable" style="width: 100%; text-align:center;"
| |
| − | !Study
| |
| − | ![[Levels_of_Evidence#Evidence|Evidence]]
| |
| − | |-
| |
| − | |[http://ascopubs.org/doi/full/10.1200/JCO.2017.77.6112 Lancet et al. 2018 (CLTR0310-301)]
| |
| − | | style="background-color:#91cf61" |Non-randomized portion of RCT
| |
| − | |-
| |
| − | |}
| |
| − | ====Preceding treatment====
| |
| − | *[[#CPX-351_monotherapy|CPX-351 monotherapy induction]]
| |
| − | ====Chemotherapy====
| |
| − | *[[Cytarabine and daunorubicin liposomal (Vyxeos)|CPX-351 (Vyxeos)]] 65 units/m<sup>2</sup> over 90 minutes IV once per day on days 1 & 3
| |
| − | | |
| − | '''Up to two courses'''
| |
| − | | |
| − | ===References===
| |
| − | <!-- # '''Abstract:''' Lancet JE, Uy GL, Cortes JE, Newell LF, Lin TL, Ritchie EK, Stuart RK, Strickland SA, Hogge D, Solomon SR, Stone RM, Bixby DL, Kolitz JE, Schiller GJ, Wieduwilt MJ, Ryan DH, Hoering A, Chiarella M, Louie AC, Medeiros BC. Final results of a phase III randomized trial of CPX-351 versus 7+3 in older patients with newly diagnosed high risk (secondary) AML. J Clin Oncol. 2016 34:15_suppl, 7000-7000 [http://ascopubs.org/doi/abs/10.1200/JCO.2016.34.15_suppl.7000 link to abstract] '''contains partial protocol''' [https://clinicaltrials.gov/ct2/show/NCT01696084 ClinicalTrials.gov] -->
| |
| − | # '''CLTR0310-301:''' Lancet JE, Uy GL, Cortes JE, Newell LF, Lin TL, Ritchie EK, Stuart RK, Strickland SA, Hogge D, Solomon SR, Stone RM, Bixby DL, Kolitz JE, Schiller GJ, Wieduwilt MJ, Ryan DH, Hoering A, Banerjee K, Chiarella M, Louie AC, Medeiros BC. CPX-351 (cytarabine and daunorubicin) liposome for injection versus conventional cytarabine plus daunorubicin in older patients with newly diagnosed secondary acute myeloid leukemia. J Clin Oncol. 2018 Jul 19:JCO2017776112. [Epub ahead of print] [http://ascopubs.org/doi/full/10.1200/JCO.2017.77.6112 link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/300024784 PubMed]
| |
| − | | |
| − | ==Cytarabine & Daunorubicin {{#subobject:d6f810|Regimen=1}}==
| |
| − | {| class="wikitable" style="float:right; margin-left: 5px;"
| |
| − | |-
| |
| − | |[[#top|back to top]]
| |
| − | |}
| |
| − | ===Variant #1 {{#subobject:c39b55|Variant=1}}===
| |
| − | {| class="wikitable" style="width: 100%; text-align:center;"
| |
| − | !Study
| |
| − | ![[Levels_of_Evidence#Evidence|Evidence]]
| |
| − | |-
| |
| − | |[https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(12)60485-1/fulltext Castaigne et al. 2012 (ALFA-0701)]
| |
| − | | style="background-color:#91cf61" |Non-randomized portion of RCT
| |
| − | |-
| |
| − | |}
| |
| − | ''Note: the preceding treatment is not a true randomization because only patients in the gemtuzumab ozogamicin arm with platelet count less than 100 x 10<sup>9</sup> at day 45 from initiation of chemotherapy were assigned to this regimen. Length of courses is not specified.''
| |
| − | ====Preceding treatment====
| |
| − | *[[#7.2B3d_.28intermediate-dose.29|7+3d (intermediate-dose)]] or [[#7.2B3d_.26_GO|7+3d & GO]] induction
| |
| − | ====Chemotherapy====
| |
| − | *[[Cytarabine (Cytosar)]] 1000 mg/m<sup>2</sup> IV every 12 hours on days 1 to 4 (8 total doses)
| |
| − | *[[Daunorubicin (Cerubidine)]] as follows:
| |
| − | **Course 1: 60 mg/m<sup>2</sup> IV once on day 1
| |
| − | **Course 2: 60 mg/m<sup>2</sup> IV once per day on days 1 & 2
| |
| − | | |
| − | '''2 courses'''
| |
| − | | |
| − | ===Variant #2 {{#subobject:59874e|Variant=1}}===
| |
| − | {| class="wikitable" style="width: 100%; text-align:center;"
| |
| − | !Study
| |
| − | ![[Levels_of_Evidence#Evidence|Evidence]]
| |
| − | !Comparator
| |
| − | ![[Levels_of_Evidence#Efficacy|Efficacy]]
| |
| − | |-
| |
| − | |[http://www.bloodjournal.org/content/109/12/5129.full Gardin et al. 2007 (ALFA 9803)]
| |
| − | | style="background-color:#1a9851" |Phase III (E)
| |
| − | |4 + 7 with daunorubicin
| |
| − | | style="background-color:#91cf60" |Seems to have superior OS
| |
| − | |-
| |
| − | |}
| |
| − | ====Preceding treatment====
| |
| − | *4d + 7 induction
| |
| − | ====Chemotherapy====
| |
| − | *[[Cytarabine (Cytosar)]] 60 mg/m<sup>2</sup> SC every 12 hours on days 1 to 5 (10 total doses)
| |
| − | *[[Daunorubicin (Cerubidine)]] 45 mg/m<sup>2</sup> IV once on day 1
| |
| − | | |
| − | '''1-month cycle for 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. [http://www.bloodjournal.org/content/109/12/5129.full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/17341661 PubMed]
| |
| − | # '''ALFA-0701:''' Castaigne S, Pautas C, Terré C, Raffoux E, Bordessoule D, Bastie JN, Legrand O, Thomas X, Turlure P, Reman O, de Revel T, Gastaud L, de Gunzburg N, Contentin N, Henry E, Marolleau JP, Aljijakli A, Rousselot P, Fenaux P, Preudhomme C, Chevret S, Dombret H; Acute Leukemia French Association. Effect of gemtuzumab ozogamicin on survival of adult patients with de-novo acute myeloid leukaemia (ALFA-0701): a randomised, open-label, phase 3 study. Lancet. 2012 Apr 21;379(9825):1508-16. [https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(12)60485-1/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/22482940 PubMed]
| |
| − | | |
| − | ==Cytarabine, Daunorubicin, Gemtuzumab ozogamicin {{#subobject:0f7f87|Regimen=1}}==
| |
| − | {| class="wikitable" style="float:right; margin-left: 5px;"
| |
| − | |-
| |
| − | |[[#top|back to top]]
| |
| − | |}
| |
| − | ===Regimen {{#subobject:c56261|Variant=1}}===
| |
| − | {| class="wikitable" style="width: 100%; text-align:center;"
| |
| − | !Study
| |
| − | ![[Levels_of_Evidence#Evidence|Evidence]]
| |
| − | |-
| |
| − | |[https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(12)60485-1/fulltext Castaigne et al. 2012 (ALFA-0701)]
| |
| − | | style="background-color:#91cf61" |Non-randomized portion of RCT
| |
| − | |-
| |
| − | |}
| |
| − | ''Note: length of courses is not specified.''
| |
| − | ====Preceding treatment====
| |
| − | *[[#7.2B3d_.26_GO|7+3d & GO]] induction
| |
| − | | |
| − | ====Chemotherapy====
| |
| − | *[[Cytarabine (Cytosar)]] 1000 mg/m<sup>2</sup> IV every 12 hours on days 1 to 4 (8 total doses)
| |
| − | *[[Daunorubicin (Cerubidine)]] as follows:
| |
| − | **Course 1: 60 mg/m<sup>2</sup> IV once on day 1
| |
| − | **Course 2: 60 mg/m<sup>2</sup> IV once per day on days 1 & 2
| |
| − | *[[Gemtuzumab ozogamicin (Mylotarg)]] 3 mg/m<sup>2</sup> (maximum dose of 5 mg) IV once on day 1
| |
| − | | |
| − | '''2 courses'''
| |
| − | | |
| − | ===References===
| |
| − | # '''ALFA-0701:''' Castaigne S, Pautas C, Terré C, Raffoux E, Bordessoule D, Bastie JN, Legrand O, Thomas X, Turlure P, Reman O, de Revel T, Gastaud L, de Gunzburg N, Contentin N, Henry E, Marolleau JP, Aljijakli A, Rousselot P, Fenaux P, Preudhomme C, Chevret S, Dombret H; Acute Leukemia French Association. Effect of gemtuzumab ozogamicin on survival of adult patients with de-novo acute myeloid leukaemia (ALFA-0701): a randomised, open-label, phase 3 study. Lancet. 2012 Apr 21;379(9825):1508-16. [https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(12)60485-1/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/22482940 PubMed]
| |
| − | | |
| − | ==CYVE {{#subobject:f8d436|Regimen=1}}==
| |
| − | {| class="wikitable" style="float:right; margin-left: 5px;"
| |
| − | |-
| |
| − | |[[#top|back to top]]
| |
| − | |}
| |
| − | CYVE: '''<u>CY</u>'''tarabine & '''<u>VE</u>'''pesid (Etoposide)
| |
| − | ===Regimen {{#subobject:79438d|Variant=1}}===
| |
| − | {| class="wikitable" style="width: 100%; text-align:center;"
| |
| − | !Study
| |
| − | ![[Levels_of_Evidence#Evidence|Evidence]]
| |
| − | |-
| |
| − | |[http://ascopubs.org/doi/full/10.1200/JCO.2017.72.8618 Lee et al. 2017 (COSAH C-022)]
| |
| − | | style="background-color:#91cf61" |Non-randomized portion of RCT
| |
| − | |-
| |
| − | |}
| |
| − | ''Note: this consolidaton regimen was for patients with high-risk cytogenetics.''
| |
| − | ====Preceding treatment====
| |
| − | *[[#7.2B3d_.28high-dose.29|7+3d (high-dose)]] versus [[#7.2B3i|7+3i]]
| |
| − | <div class="toccolours" style="width:100%; overflow:auto;">
| |
| − | ====Chemotherapy====
| |
| − | *[[Cytarabine (Cytosar)]] 1000 mg/m<sup>2</sup> IV once per day on days 1 to 6
| |
| − | *[[Etoposide (Vepesid)]] 150 mg/m<sup>2</sup> IV once per day on days 1 to 3
| |
| − | | |
| − | '''4 courses'''
| |
| − | </div>
| |
| − | ====Subsequent treatment====
| |
| − | *Transplant eligible patients with available donors usually proceeded to [[#Allogeneic_hematopoietic_stem_cell_transplant|allogeneic HSCT]] after 2 courses (details not specified)
| |
| − | | |
| − | ===References===
| |
| − | # '''COSAH C-022:''' Lee JH, Kim H, Joo YD, Lee WS, Bae SH, Zang DY, Kwon J, Kim MK, Lee J, Lee GW, Lee JH, Choi Y, Kim DY, Hur EH, Lim SN, Lee SM, Ryoo HM, Kim HJ, Hyun MS, Lee KH; Cooperative Study Group A for Hematology. Prospective randomized comparison of idarubicin and high-dose daunorubicin in induction chemotherapy for newly diagnosed acute myeloid leukemia. J Clin Oncol. 2017 Aug 20;35(24):2754-2763. Epub 2017 Jun 20. [http://ascopubs.org/doi/full/10.1200/JCO.2017.72.8618 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/28632487 PubMed]
| |
| − | | |
| − | ==Cytarabine & Idarubicin {{#subobject:f8c456|Regimen=1}}==
| |
| − | {| class="wikitable" style="float:right; margin-left: 5px;"
| |
| − | |-
| |
| − | |[[#top|back to top]]
| |
| − | |}
| |
| − | ===Regimen {{#subobject:099908|Variant=1}}===
| |
| − | {| class="wikitable" style="width: 100%; text-align:center;"
| |
| − | !Study
| |
| − | ![[Levels_of_Evidence#Evidence|Evidence]]
| |
| − | !Comparator
| |
| − | ![[Levels_of_Evidence#Efficacy|Efficacy]]
| |
| − | |-
| |
| − | |[http://www.bloodjournal.org/content/109/12/5129.full Gardin et al. 2007 (ALFA 9803)]
| |
| − | | style="background-color:#1a9851" |Phase III (E)
| |
| − | |4 + 7 with idarubicin
| |
| − | | style="background-color:#91cf60" |Seems to have superior OS
| |
| − | |-
| |
| − | |}
| |
| − | ====Preceding treatment====
| |
| − | *4i + 7 induction
| |
| − | ====Chemotherapy====
| |
| − | *[[Cytarabine (Cytosar)]] 60 mg/m<sup>2</sup> SC every 12 hours on days 1 to 5 (10 total doses)
| |
| − | *[[Idarubicin (Idamycin)]] 9 mg/m<sup>2</sup> IV once on day 1
| |
| − | | |
| − | '''1-month cycle for 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. [http://www.bloodjournal.org/content/109/12/5129.full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/17341661 PubMed]
| |
| − | | |
| − | ==Cytarabine, Idarubicin, Sorafenib {{#subobject:8c0061|Regimen=1}}==
| |
| − | {| class="wikitable" style="float:right; margin-left: 5px;"
| |
| − | |-
| |
| − | |[[#top|back to top]]
| |
| − | |}
| |
| − | ===Regimen {{#subobject:97a478|Variant=1}}===
| |
| − | {| class="wikitable" style="width: 100%; text-align:center;"
| |
| − | !Study
| |
| − | ![[Levels_of_Evidence#Evidence|Evidence]]
| |
| − | |-
| |
| − | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2930809/ Ravandi et al. 2010]
| |
| − | | style="background-color:#91cf61" |Phase I/II
| |
| − | |-
| |
| − | |}
| |
| − | ''Regimen details are from the phase II part of the published phase I/II trial.''
| |
| − | ====Preceding treatment====
| |
| − | *[[#7.2B3i_.26_Sorafenib|7+3i & Sorafenib induction]]
| |
| − | ====Chemotherapy====
| |
| − | *[[Cytarabine (Cytosar)]] 750 mg/m<sup>2</sup>/day IV continuous infusion on days 1 to 3 (total dose: 2250 mg/m<sup>2</sup>)
| |
| − | *[[Idarubicin (Idamycin)]] 8 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1 & 2
| |
| − | *[[Sorafenib (Nexavar)]] 400 mg PO BID "for up to 28 days"
| |
| − | | |
| − | '''4 to 6-week cycle for up to 5 cycles'''
| |
| | ====Subsequent treatment==== | | ====Subsequent treatment==== |
| | *[[#Sorafenib_monotherapy|Sorafenib maintenance]] | | *[[#Sorafenib_monotherapy|Sorafenib maintenance]] |
| | | | |
| | ===References=== | | ===References=== |
| − | <!-- no pre-pub disclosed -->
| + | # '''CALGB 11001:''' Uy GL, Mandrekar SJ, Laumann K, Marcucci G, Zhao W, Levis MJ, Klepin HD, Baer MR, Powell BL, Westervelt P, DeAngelo DJ, Stock W, Sanford B, Blum WG, Bloomfield CD, Stone RM, Larson RA. A phase 2 study incorporating sorafenib into the chemotherapy for older adults with FLT3-mutated acute myeloid leukemia: CALGB 11001. Blood Adv. 2017 Jan 24;1(5):331-340. [http://www.bloodadvances.org/content/1/5/331 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5637402/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/29034366 PubMed] |
| − | # 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. Epub 2010 Mar 8. [http://jco.ascopubs.org/content/28/11/1856.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2930809/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/20212254 PubMed] | |
| − | ## '''Update:''' Ravandi F, Arana Yi C, Cortes JE, Levis M, Faderl S, Garcia-Manero G, Jabbour E, Konopleva M, O'Brien S, Estrov Z, Borthakur G, Thomas D, Pierce S, Brandt M, Pratz K, Luthra R, Andreeff M, Kantarjian H. Final report of phase II study of sorafenib, cytarabine and idarubicin for initial therapy in younger patients with acute myeloid leukemia. Leukemia. 2014 Jul;28(7):1543-5. Epub 2014 Feb 3. [https://www.nature.com/leu/journal/v28/n7/full/leu201454a.html link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4091714/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/24487412 PubMed]
| |
| − | | |
| − | ==Cytarabine, Idarubicin, Vorinostat {{#subobject:5fc722|Regimen=1}}==
| |
| − | {| class="wikitable" style="float:right; margin-left: 5px;"
| |
| − | |-
| |
| − | |[[#top|back to top]]
| |
| − | |}
| |
| − | ===Regimen {{#subobject:44ee8a|Variant=1}}===
| |
| − | {| class="wikitable" style="width: 100%; text-align:center;"
| |
| − | !Study
| |
| − | ![[Levels_of_Evidence#Evidence|Evidence]]
| |
| − | |-
| |
| − | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4879705/ Garcia-Manero et al. 2012]
| |
| − | | style="background-color:#91cf61" |Phase II
| |
| − | |-
| |
| − | |}
| |
| − | ====Preceding treatment====
| |
| − | *[[#7.2B3i_.26_Vorinostat|7+3i & Vorinostat induction]]
| |
| − | ====Chemotherapy====
| |
| − | *[[Cytarabine (Cytosar)]] 750 mg/m<sup>2</sup>/day IV continuous infusion on days 4 to 6 (total dose: 2250 mg/m<sup>2</sup>)
| |
| − | *[[Idarubicin (Idamycin)]] 8 mg/m<sup>2</sup> IV once per day on days 4 & 5
| |
| − | *[[Vorinostat (Zolinza)]] 500 mg PO TID on days 1 to 3
| |
| − | | |
| − | ====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 (Cytosar)]] to prevent fever and rash
| |
| − | | |
| − | '''6-day course for up to 5 cycles'''
| |
| − | ====Subsequent treatment====
| |
| − | *[[#Vorinostat_monotherapy|Vorinostat maintenance]]
| |
| − | | |
| − | ===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. [http://jco.ascopubs.org/content/30/18/2204.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4879705/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/22585696 PubMed]
| |
| − | | |
| − | ==Etoposide & Mitoxantrone {{#subobject:ab1766|Regimen=1}}==
| |
| − | {| class="wikitable" style="float:right; margin-left: 5px;"
| |
| − | |-
| |
| − | |[[#top|back to top]]
| |
| − | |}
| |
| − | ===Regimen {{#subobject:780933|Variant=1}}===
| |
| − | {| class="wikitable" style="width: 100%; text-align:center;"
| |
| − | !Study
| |
| − | ![[Levels_of_Evidence#Evidence|Evidence]]
| |
| − | !Comparator
| |
| − | ![[Levels_of_Evidence#Efficacy|Efficacy]]
| |
| − | |-
| |
| − | |[http://www.bloodjournal.org/content/118/23/6037.long Vellenga et al. 2011 (HOVON-SAKK AML-29/AML-42)]
| |
| − | | style="background-color:#1a9851" |Phase III (C)
| |
| − | |[[#Busulfan_.26_Cyclophosphamide.2C_then_auto_HSCT|Bu/Cy, then auto HSCT]]
| |
| − | | style="background-color:#fee08b" |Might have inferior RFS
| |
| − | |-
| |
| − | |}
| |
| − | ====Preceding treatment====
| |
| − | *[[#7.2B3i|7+3i]], then Amsacrine & Cytarabine
| |
| − | ====Chemotherapy====
| |
| − | *[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV once per day on days 1 to 5
| |
| − | *[[Mitoxantrone (Novantrone)]] 10 mg/m<sup>2</sup> IV once per day on days 1 to 5
| |
| − | | |
| − | ===References===
| |
| − | # '''HOVON-SAKK AML-29/AML-42:''' Vellenga E, van Putten W, Ossenkoppele GJ, Verdonck LF, Theobald M, Cornelissen JJ, Huijgens PC, Maertens J, Gratwohl A, Schaafsma R, Schanz U, Graux C, Schouten HC, Ferrant A, Bargetzi M, Fey MF, Löwenberg B; Dutch-Belgian Hemato-Oncology Cooperative Group (HOVON).; Swiss Group for Clinical Cancer Research Collaborative Group (SAKK). Autologous peripheral blood stem cell transplantation for acute myeloid leukemia. Blood. 2011 Dec 1;118(23):6037-42. Epub 2011 Sep 27. [http://www.bloodjournal.org/content/118/23/6037.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/21951683 PubMed]
| |
| − | | |
| − | ==HAM {{#subobject:1da5a5|Regimen=1}}==
| |
| − | {| class="wikitable" style="float:right; margin-left: 5px;"
| |
| − | |-
| |
| − | |[[#top|back to top]]
| |
| − | |}
| |
| − | HAM: '''<u>H</u>'''igh-dose '''<u>A</u>'''ra-C (Cytarabine), '''<u>M</u>'''itoxantrone
| |
| − | | |
| − | ===Regimen {{#subobject:eb86c6|Variant=1}}===
| |
| − | {| class="wikitable" style="width: 100%; text-align:center;"
| |
| − | !Study
| |
| − | ![[Levels_of_Evidence#Evidence|Evidence]]
| |
| − | |-
| |
| − | |[https://onlinelibrary.wiley.com/doi/10.1111/j.1600-0609.2007.00988.x/abstract Wierzbowksa et al. 2007]
| |
| − | | style="background-color:#91cf61" |Phase II
| |
| − | |-
| |
| − | |[http://jco.ascopubs.org/content/30/20/2441.full Holowiecki et al. 2012 (PALG AML1/2004)]
| |
| − | | style="background-color:#91cf61" |Non-randomized portion of RCT
| |
| − | |-
| |
| − | |}
| |
| − | ====Preceding treatment====
| |
| − | *Wierzbowska et al. 2007: [[#CLAG-M|CLAG-M]]
| |
| − | *PALG AML1/2004: [[#7.2B3d_.28intermediate-dose.29|DA]] versus [[#DAC|DAC]] versus DAF
| |
| − | | |
| − | ====Chemotherapy====
| |
| − | *[[Cytarabine (Cytosar)]] 1500 mg/m<sup>2</sup> IV once per day on days 1 to 3
| |
| − | *[[Mitoxantrone (Novantrone)]] 10 mg/m<sup>2</sup> IV once per day on days 3 to 5
| |
| − | ====Subsequent treatment====
| |
| − | *[[#HiDAC|HiDAC consolidation]]
| |
| − | | |
| − | ===References===
| |
| − | # Wierzbowska A, Robak T, Pluta A, Wawrzyniak E, Cebula B, Holowiecki J, Kyrcz-Krzemien S, Grosicki S, Giebel S, Skotnicki AB, Piatkowska-Jakubas B, Kuliczkowski K, Kielbinski M, Zawilska K, Kloczko 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. [https://onlinelibrary.wiley.com/doi/10.1111/j.1600-0609.2007.00988.x/abstract link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/18076637 PubMed] content property of [http://hemonc.org HemOnc.org]
| |
| − | # '''PALG AML1/2004:''' Holowiecki J, Grosicki S, Giebel S, Robak T, Kyrcz-Krzemien S, Kuliczkowski K, Skotnicki AB, Hellmann A, Sulek K, Dmoszyńska 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. J Clin Oncol. 2012 Jul 10;30(20):2441-8. Epub 2012 Apr 16. [http://jco.ascopubs.org/content/30/20/2441.full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/22508825 PubMed]
| |
| − | | |
| − | ==HDAC & G-CSF {{#subobject:e0396d|Regimen=1}}==
| |
| − | {| class="wikitable" style="float:right; margin-left: 5px;"
| |
| − | |-
| |
| − | |[[#top|back to top]]
| |
| − | |}
| |
| − | HDAC & G-CSF: '''<u>H</u>'''igh '''<u>D</u>'''ose '''<u>A</u>'''ra-'''<u>C</u>''' (Cytarabine) & '''<u>G</u>'''ranulocyte '''<u>C</u>'''olony '''<u>S</u>'''timulating '''<u>F</u>'''actor
| |
| − | | |
| − | ===Regimen {{#subobject:d8edc4|Variant=1}}===
| |
| − | {| class="wikitable" style="width: 100%; text-align:center;"
| |
| − | !Study
| |
| − | ![[Levels_of_Evidence#Evidence|Evidence]]
| |
| − | !Comparator
| |
| − | ![[Levels_of_Evidence#Efficacy|Efficacy]]
| |
| − | |-
| |
| − | |[http://ascopubs.org/doi/full/10.1200/JCO.2016.70.4551 Thomas et al. 2017 (ALFA-0702)]
| |
| − | | style="background-color:#1a9851" |Randomized Phase II (C)
| |
| − | |[[#CLARA|CLARA]]
| |
| − | | style="background-color:#fc8d59" |Seems to have inferior RFS
| |
| − | |-
| |
| − | |}
| |
| − | ====Preceding treatment====
| |
| − | *Cytarabine, Daunorubicin, G-CSF induction
| |
| − | ====Chemotherapy====
| |
| − | *[[Cytarabine (Cytosar)]] 3000 mg/m<sup>2</sup> IV over 3 hours Q12H on days 1, 3, 5 (6 total doses)
| |
| − | *[[Filgrastim (Neupogen)]] 5 mcg/kg IV once per day on days 1 to 5
| |
| − | | |
| − | '''35-day cycle for 3 cycles'''
| |
| − | | |
| − | ===References===
| |
| − | # '''ALFA-0702:''' Thomas X, de Botton S, Chevret S, Caillot D, Raffoux E, Lemasle E, Marolleau JP, Berthon C, Pigneux A, Vey N, Reman O, Simon M, Recher C, Cahn JY, Hermine O, Castaigne S, Celli-Lebras K, Ifrah N, Preudhomme C, Terré C, Dombret H. Randomized phase II study of clofarabine-based consolidation for younger adults with acute myeloid leukemia in first remission. J Clin Oncol. 2017 Apr 10;35(11):1223-1230. Epub 2017 Feb 21. [http://ascopubs.org/doi/full/10.1200/JCO.2016.70.4551 link to original article] '''contains verified protocol in supplement''' [https://www.ncbi.nlm.nih.gov/pubmed/28221862 PubMed]
| |
| − | | |
| − | ==HiDAC {{#subobject:caa3a2|Regimen=1}}==
| |
| − | {| class="wikitable" style="float:right; margin-left: 5px;"
| |
| − | |-
| |
| − | |[[#top|back to top]]
| |
| − | |}
| |
| − | HiDAC: '''<u>Hi</u>'''gh '''<u>D</u>'''ose '''<u>A</u>'''ra-'''<u>C</u>''' (Cytarabine)
| |
| − | <br>HDAC: '''<u>H</u>'''igh '''<u>D</u>'''ose '''<u>A</u>'''ra-'''<u>C</u>''' (Cytarabine)
| |
| − | <br>HDAraC: '''<u>H</u>'''igh '''<u>D</u>'''ose '''<u>AraC</u>''' (Cytarabine)
| |
| − | ===Variant #1, 2000 mg/m<sup>2</sup> q12h x 6 {{#subobject:4e73ae|Variant=1}}===
| |
| − | {| class="wikitable" style="width: 100%; text-align:center;"
| |
| − | !Study
| |
| − | ![[Levels_of_Evidence#Evidence|Evidence]]
| |
| − | |-
| |
| − | |[http://jco.ascopubs.org/content/30/20/2441.full Holowiecki et al. 2012]
| |
| − | | style="background-color:#91cf61" |Non-randomized
| |
| − | |-
| |
| − | |}
| |
| − | ''Details in the text are scant.''
| |
| − | ====Preceding treatment====
| |
| − | *[[#Cytarabine_.26_Mitoxantrone|Cytarabine & Mitoxantrone consolidation]]
| |
| − | ====Chemotherapy====
| |
| − | *[[Cytarabine (Cytosar)]] 2000 mg/m<sup>2</sup> IV Q12H on days 1, 3, 5 (6 total doses)
| |
| − | | |
| − | ===Variant #2, 2 cycles of 2000 mg/m<sup>2</sup> q12h x 10 {{#subobject:2a4b32|Variant=1}}===
| |
| − | {| class="wikitable" style="width: 100%; text-align:center;"
| |
| − | !Study
| |
| − | ![[Levels_of_Evidence#Evidence|Evidence]]
| |
| − | !Comparator
| |
| − | ![[Levels_of_Evidence#Efficacy|Efficacy]]
| |
| − | |-
| |
| − | |[http://ar.iiarjournals.org/content/32/2/643.long Fukushima et al. 2012]
| |
| − | | style="background-color:#91cf61" |Randomized, <20 pts in this arm (C)
| |
| − | |[[#IDAC|mIDAC]]
| |
| − | | style="background-color:#ffffbf" |Seems not superior
| |
| − | |-
| |
| − | |}
| |
| − | ====Preceding treatment====
| |
| − | *BHAC-MMV
| |
| − | ====Chemotherapy====
| |
| − | *[[Cytarabine (Cytosar)]] 2000 mg/m<sup>2</sup> IV over 60 minutes q12h on days 1 to 5 (10 total doses)
| |
| − | | |
| − | '''2 cycles'''
| |
| − | ====Subsequent treatment====
| |
| − | *A-VVV
| |
| − | | |
| − | ===Variant #3, 3 cycles of 3000 mg/m<sup>2</sup> q12h x 6 {{#subobject:746f61|Variant=1}}===
| |
| − | {| class="wikitable" style="width: 100%; text-align:center;"
| |
| − | !Study
| |
| − | ![[Levels_of_Evidence#Evidence|Evidence]]
| |
| − | !Comparator
| |
| − | ![[Levels_of_Evidence#Efficacy|Efficacy]]
| |
| − | |-
| |
| − | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1895015/ Moore et al. 2004 (CALGB 9222)]
| |
| − | | style="background-color:#1a9851" |Phase III (C)
| |
| − | |HiDAC, then CYVE, then AZQ & Mitoxantrone
| |
| − | | style="background-color:#ffffbf" |Seems not superior
| |
| − | |-
| |
| − | |[http://ascopubs.org/doi/full/10.1200/JCO.2012.46.4743 Schaich et al. 2013 (AML2003)]
| |
| − | | style="background-color:#1a9851" |Phase III (C)
| |
| − | |MAC/MAMAC/MAC
| |
| − | | style="background-color:#ffffbf" |Seems not superior
| |
| − | |-
| |
| − | |[http://jco.ascopubs.org/content/33/11/1252.full Stone et al. 2015 (ACCEDE)]
| |
| − | | style="background-color:#91cf61" |Non-randomized portion of RCT
| |
| − | | style="background-color:#d3d3d3" |
| |
| − | | style="background-color:#d3d3d3" |
| |
| − | |-
| |
| − | |[https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(15)00362-9/fulltext Röllig et al. 2015 (SORAML)]
| |
| − | | style="background-color:#1a9851" |Randomized Phase II (C)
| |
| − | |HiDAC & Sorafenib
| |
| − | | style="background-color:#fc8d59" |Seems to have inferior EFS
| |
| − | |-
| |
| − | |[http://ascopubs.org/doi/full/10.1200/JCO.2017.72.8618 Stone et al. 2015 (COSAH C-022)]
| |
| − | | style="background-color:#91cf61" |Non-randomized portion of RCT
| |
| − | | style="background-color:#d3d3d3" |
| |
| − | | style="background-color:#d3d3d3" |
| |
| − | |-
| |
| − | |}
| |
| − | ''Note: CALGB 9222 specified that each cycle begins within 2 weeks after hematopoietic recovery from the preceding cycle. SORAML specified a 28-day (minimum) cycle or 1 week after marrow recovery, whichever comes later.''
| |
| − | ====Preceding treatment====
| |
| − | *CALGB 9222: [[#7.2B3d_.28standard-dose.29|7+3d (standard-dose)]]
| |
| − | *AML2003: [[#7.2B3d_.28intermediate-dose.29|7+3d (intermediate-dose)]] x 2
| |
| − | *ACCEDE: Amonafide & Cytarabine versus [[#7.2B3d_.28standard-dose.29|7+3d (standard-dose)]]
| |
| − | *SORAML: [[#7.2B3d_.28intermediate-dose.29|7+3d (intermediate-dose)]] versus 7+3d & Sorafenib
| |
| − | *COSAH C-022: [[#7.2B3d_.28high-dose.29|7+3d (high-dose)]] versus [[#7.2B3i|7+3i]]
| |
| − | ====Chemotherapy====
| |
| − | *[[Cytarabine (Cytosar)]] 3000 mg/m<sup>2</sup> IV over 3 hours q12h on days 1, 3, 5 (6 total doses)
| |
| − | | |
| − | '''3 cycles of varying durations'''
| |
| − | | |
| − | ===Variant #4, 3 cycles of 2000 mg/m<sup>2</sup> q12h x 10 {{#subobject:8887b8|Variant=1}}===
| |
| − | {| class="wikitable" style="width: 100%; text-align:center;"
| |
| − | !Study
| |
| − | ![[Levels_of_Evidence#Evidence|Evidence]]
| |
| − | !Comparator
| |
| − | ![[Levels_of_Evidence#Efficacy|Efficacy]]
| |
| − | |-
| |
| − | |[http://www.bloodjournal.org/content/117/8/2366.long Miyawaki et al. 2010 (JALSG AML201)]
| |
| − | | style="background-color:#1a9851" |Phase III (E)
| |
| − | |Multiagent chemotherapy
| |
| − | | style="background-color:#ffffbf" |Seems not superior
| |
| − | |-
| |
| − | |}
| |
| − | ''Note: this was considered an experimental arm in Japan, given the timing of HiDAC approval.''
| |
| − | ====Preceding treatment====
| |
| − | *7+5d or [[#7.2B3i|7+3i]]
| |
| − | ====Chemotherapy====
| |
| − | *[[Cytarabine (Cytosar)]] 2000 mg/m<sup>2</sup> IV over 3 hours q12h on days 1 to 5 (10 total doses)
| |
| − | | |
| − | '''3 cycles, started 1 week after neutrophils, WBCs, and platelets recovered to more than 1500/uL, 3 × 10<sup>9</sup>/L, and 100 × 10<sup>9</sup>/L'''
| |
| − | | |
| − | ===Variant #5, 4 cycles of 3000 mg/m<sup>2</sup> q12h x 6 {{#subobject:0c2779|Variant=1}}===
| |
| − | {| class="wikitable" style="width: 100%; text-align:center;"
| |
| − | !Study
| |
| − | ![[Levels_of_Evidence#Evidence|Evidence]]
| |
| − | !Comparator
| |
| − | ![[Levels_of_Evidence#Efficacy|Efficacy]]
| |
| − | |-
| |
| − | |[http://www.nejm.org/doi/full/10.1056/NEJM199410063311402 Mayer et al. 1994]
| |
| − | | style="background-color:#1a9851" |Phase III (E)
| |
| − | |Low-dose continuous infusion cytarabine
| |
| − | | style="background-color:#91cf60" |Seems to have superior OS
| |
| − | |-
| |
| − | |[http://www.bloodjournal.org/content/118/7/1754.long Thomas et al. 2011 (ALFA-9802)]
| |
| − | | style="background-color:#1a9851" |Phase III (C)
| |
| − | |Timed sequential chemotherapy (TSC)
| |
| − | | style="background-color:#ffffbf" |Seems not superior
| |
| − | |-
| |
| − | |[http://ascopubs.org/doi/full/10.1200/JCO.2017.72.8618 Lee et al. 2017 (COSAH C-022)]
| |
| − | | style="background-color:#91cf61" |Non-randomized portion of RCT
| |
| − | | style="background-color:#d3d3d3" |
| |
| − | | style="background-color:#d3d3d3" |
| |
| − | |-
| |
| − | |}
| |
| − | ====Preceding treatment====
| |
| − | *ALFA-9802: Timed sequential therapy +/- GM-CSF priming
| |
| − | *COSAH C-022: [[#7.2B3d_.28high-dose.29|7+3d (high-dose)]] versus [[#7.2B3i|7+3i]]
| |
| − | ====Chemotherapy====
| |
| − | *[[Cytarabine (Cytosar)]] 3000 mg/m<sup>2</sup> IV over 3 hours q12h on days 1, 3, 5 (6 total doses)
| |
| − | | |
| − | '''Up to 4 cycles'''
| |
| − | ====Subsequent treatment====
| |
| − | *ALFA-9802: Cytarabine & Daunorubicin maintenance
| |
| − | ===References===
| |
| − | # Mayer RJ, Davis RB, Schiffer CA, Berg DT, Powell BL, Schulman P, Omura GA, Moore JO, McIntyre OR, Frei E 3rd; Cancer and Leukemia Group B. Intensive postremission chemotherapy in adults with acute myeloid leukemia. N Engl J Med. 1994 Oct 6;331(14):896-903. [http://www.nejm.org/doi/full/10.1056/NEJM199410063311402 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/8078551 PubMed]
| |
| − | # '''CALGB 9222:''' Moore JO, George SL, Dodge RK, Amrein PC, Powell BL, Kolitz JE, Baer MR, Davey FR, Bloomfield CD, Larson RA, Schiffer CA. Sequential multiagent chemotherapy is not superior to high-dose cytarabine alone as postremission intensification therapy for acute myeloid leukemia in adults under 60 years of age: Cancer and Leukemia Group B Study 9222. Blood. 2005 May 1;105(9):3420-7. Epub 2004 Nov 30. [http://www.bloodjournal.org/content/105/9/3420.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1895015/ link to PMC article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/15572587 PubMed]
| |
| − | # '''JALSG AML201:''' Miyawaki S, Ohtake S, Fujisawa S, Kiyoi H, Shinagawa K, Usui N, Sakura T, Miyamura K, Nakaseko C, Miyazaki Y, Fujieda A, Nagai T, Yamane T, Taniwaki M, Takahashi M, Yagasaki F, Kimura Y, Asou N, Sakamaki H, Handa H, Honda S, Ohnishi K, Naoe T, Ohno R. A randomized comparison of 4 courses of standard-dose multiagent chemotherapy versus 3 courses of high-dose cytarabine alone in postremission therapy for acute myeloid leukemia in adults: the JALSG AML201 Study. Blood. 2011 Feb 24;117(8):2366-72. Epub 2010 Dec 29. [http://www.bloodjournal.org/content/117/8/2366.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/21190996 PubMed]
| |
| − | # '''ALFA-9802:''' Thomas X, Elhamri M, Raffoux E, Renneville A, Pautas C, de Botton S, de Revel T, Reman O, Terré C, Gardin C, Chelghoum Y, Boissel N, Quesnel B, Hicheri Y, Bourhis JH, Fenaux P, Preudhomme C, Michallet M, Castaigne S, Dombret H. Comparison of high-dose cytarabine and timed-sequential chemotherapy as consolidation for younger adults with AML in first remission: the ALFA-9802 study. Blood. 2011 Aug 18;118(7):1754-62. Epub 2011 Jun 20. [http://www.bloodjournal.org/content/118/7/1754.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/21690555 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. [http://ar.iiarjournals.org/content/32/2/643.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/22287757 PubMed]
| |
| − | # '''AML2003:''' Schaich M, Parmentier S, Kramer M, Illmer T, Stölzel F, Röllig C, Thiede C, Hänel M, Schäfer-Eckart K, Aulitzky W, Einsele H, Ho AD, Serve H, Berdel WE, Mayer J, Schmitz N, Krause SW, Neubauer A, Baldus CD, Schetelig J, Bornhäuser M, Ehninger G. High-dose cytarabine consolidation with or without additional amsacrine and mitoxantrone in acute myeloid leukemia: results of the prospective randomized AML2003 trial. J Clin Oncol. 2013 Jun 10;31(17):2094-102. Epub 2013 Apr 29. [http://ascopubs.org/doi/full/10.1200/JCO.2012.46.4743 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/23630210 PubMed]
| |
| − | # '''ACCEDE:''' Stone RM, Mazzola E, Neuberg D, Allen SL, Pigneux A, Stuart RK, Wetzler M, Rizzieri D, Erba HP, Damon L, Jang JH, Tallman MS, Warzocha K, Masszi T, Sekeres MA, Egyed M, Horst HA, Selleslag D, Solomon SR, Venugopal P, Lundberg AS, Powell B. Phase III open-label randomized study of cytarabine in combination with amonafide l-malate or daunorubicin as induction therapy for patients with secondary acute myeloid leukemia. J Clin Oncol. 2015 Apr 10;33(11):1252-7. Epub 2015 Mar 2. [http://jco.ascopubs.org/content/33/11/1252.full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/25732165 PubMed]
| |
| − | # Holowiecki J, Grosicki S, Giebel S, Robak T, Kyrcz-Krzemien S, Kuliczkowski K, Skotnicki AB, Hellmann A, Sulek K, Dmoszyńska 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. J Clin Oncol. 2012 Jul 10;30(20):2441-8. Epub 2012 Apr 16. [http://jco.ascopubs.org/content/30/20/2441.full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/22508825 PubMed]
| |
| − | # '''SORAML:''' Röllig C, Serve H, Hüttmann A, Noppeney R, Müller-Tidow C, Krug U, Baldus CD, Brandts CH, Kunzmann V, Einsele H, Krämer A, Schäfer-Eckart K, Neubauer A, Burchert A, Giagounidis A, Krause SW, Mackensen A, Aulitzky W, Herbst R, Hänel M, Kiani A, Frickhofen N, Kullmer J, Kaiser U, Link H, Geer T, Reichle A, Junghanß C, Repp R, Heits F, Dürk H, Hase J, Klut IM, Illmer T, Bornhäuser M, Schaich M, Parmentier S, Görner M, Thiede C, von Bonin M, Schetelig J, Kramer M, Berdel WE, Ehninger G; Study Alliance Leukaemia. Addition of sorafenib versus placebo to standard therapy in patients aged 60 years or younger with newly diagnosed acute myeloid leukaemia (SORAML): a multicentre, phase 2, randomised controlled trial. Lancet Oncol. 2015 Dec;16(16):1691-9. Epub 2015 Nov 6. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(15)00362-9/fulltext link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/26549589 PubMed]
| |
| − | # '''COSAH C-022:''' Lee JH, Kim H, Joo YD, Lee WS, Bae SH, Zang DY, Kwon J, Kim MK, Lee J, Lee GW, Lee JH, Choi Y, Kim DY, Hur EH, Lim SN, Lee SM, Ryoo HM, Kim HJ, Hyun MS, Lee KH; Cooperative Study Group A for Hematology. Prospective randomized comparison of idarubicin and high-dose daunorubicin in induction chemotherapy for newly diagnosed acute myeloid leukemia. J Clin Oncol. 2017 Aug 20;35(24):2754-2763. Epub 2017 Jun 20. [http://ascopubs.org/doi/full/10.1200/JCO.2017.72.8618 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/28632487 PubMed]
| |
| − | | |
| − | ==IDAC {{#subobject:f5cd74|Regimen=1}}==
| |
| − | {| class="wikitable" style="float:right; margin-left: 5px;"
| |
| − | |-
| |
| − | |[[#top|back to top]]
| |
| − | |}
| |
| − | IDAC: '''<u>I</u>'''ntermediate '''<u>D</u>'''ose '''<u>A</u>'''ra-'''<u>C</u>''' (Cytarabine)
| |
| − | <br>mIDAC: '''<u>m</u>'''odified '''<u>I</u>'''ntermediate '''<u>D</u>'''ose '''<u>A</u>'''ra-'''<u>C</u>''' (Cytarabine)
| |
| − | | |
| − | ===Variant #1 {{#subobject:cbba35|Variant=1}}===
| |
| − | {| class="wikitable" style="width: 100%; text-align:center;"
| |
| − | !Study
| |
| − | ![[Levels_of_Evidence#Evidence|Evidence]]
| |
| − | !Comparator
| |
| − | ![[Levels_of_Evidence#Efficacy|Efficacy]]
| |
| − | |-
| |
| − | |[http://ar.iiarjournals.org/content/32/2/643.long Fukushima et al. 2012]
| |
| − | | style="background-color:#91cf61" |Randomized, <20 pts in this arm (E)
| |
| − | |[[#HiDAC|HDAC]]
| |
| − | | style="background-color:#ffffbf" |Seems not superior
| |
| − | |-
| |
| − | |}
| |
| − | ====Preceding treatment====
| |
| − | *BHAC-MMV
| |
| − | ====Chemotherapy====
| |
| − | *[[Cytarabine (Cytosar)]] 1000 mg/m<sup>2</sup> IV over 60 minutes Q12H on days 1 to 5 (10 total doses)
| |
| − | | |
| − | '''Two cycles'''
| |
| − | ====Subsequent treatment====
| |
| − | *A-VVV
| |
| − | | |
| − | ===Variant #2 {{#subobject:0340ec|Variant=1}}===
| |
| − | {| class="wikitable" style="width: 100%; text-align:center;"
| |
| − | !Study
| |
| − | ![[Levels_of_Evidence#Evidence|Evidence]]
| |
| − | |-
| |
| − | |[http://jco.ascopubs.org/content/33/11/1252.full Stone et al. 2015 (ACCEDE)]
| |
| − | | style="background-color:#91cf61" |Non-randomized portion of RCT
| |
| − | |-
| |
| − | |}
| |
| − | ====Preceding treatment====
| |
| − | *Amonafide & Cytarabine versus [[#7.2B3d_.28standard-dose.29|7+3d (standard-dose)]]
| |
| − | ====Chemotherapy====
| |
| − | *[[Cytarabine (Cytosar)]] 1000 mg/m<sup>2</sup> IV over 3 hours once per day on days 1, 3, 5 (3 total doses)
| |
| − | | |
| − | ===Variant #3 {{#subobject:22eda3|Variant=1}}===
| |
| − | {| class="wikitable" style="width: 100%; text-align:center;"
| |
| − | !Study
| |
| − | ![[Levels_of_Evidence#Evidence|Evidence]]
| |
| − | |-
| |
| − | |[http://www.nejm.org/doi/full/10.1056/NEJMoa0901409 Löwenberg et al. 2009 (HOVON 43 AML/SAKK 30/01)]
| |
| − | | style="background-color:#91cf61" |Non-randomized portion of RCT
| |
| − | |-
| |
| − | |}
| |
| − | ====Preceding treatment====
| |
| − | *[[#7.2B3d_.28standard-dose.29|7+3d (standard-dose)]] versus [[#7.2B3d_.28high-dose.29|7+3d (high-dose)]]
| |
| − | | |
| − | ====Chemotherapy====
| |
| − | *[[Cytarabine (Cytosar)]] 1000 mg/m<sup>2</sup> IV over 6 hours Q12H on days 1 to 6 (12 total doses)
| |
| − | | |
| − | '''One cycle'''
| |
| − | ====Subsequent treatment====
| |
| − | *Transplant eligible patients: [[#Allogeneic_hematopoietic_stem_cell_transplant|allogeneic HSCT]]
| |
| − | *Transplant ineligible patients: Gemtuzumab ozogamicin maintenance versus [[#Observation|no further treatment]]
| |
| − | | |
| − | ===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. 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. [http://www.nejm.org/doi/full/10.1056/NEJMoa0901409 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/19776405 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. [http://ar.iiarjournals.org/content/32/2/643.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/22287757 PubMed]
| |
| − | # '''ACCEDE:''' Stone RM, Mazzola E, Neuberg D, Allen SL, Pigneux A, Stuart RK, Wetzler M, Rizzieri D, Erba HP, Damon L, Jang JH, Tallman MS, Warzocha K, Masszi T, Sekeres MA, Egyed M, Horst HA, Selleslag D, Solomon SR, Venugopal P, Lundberg AS, Powell B. Phase III open-label randomized study of cytarabine in combination with amonafide l-malate or daunorubicin as induction therapy for patients with secondary acute myeloid leukemia. J Clin Oncol. 2015 Apr 10;33(11):1252-7. Epub 2015 Mar 2. [http://jco.ascopubs.org/content/33/11/1252.full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/25732165 PubMed]
| |
| − | | |
| − | =Maintenance after first-line therapy=
| |
| − | ''Note: with a few exceptions, these regimens are given as part of a non-curative line of therapy.''
| |
| − | ==Azacitidine monotherapy {{#subobject:887fd6|Regimen=1}}==
| |
| − | {| class="wikitable" style="float:right; margin-left: 5px;"
| |
| − | |-
| |
| − | |[[#top|back to top]]
| |
| − | |}
| |
| − | ===Regimen {{#subobject:482f11|Variant=1}}===
| |
| − | {| class="wikitable" style="width: 100%; text-align:center;"
| |
| − | !Study
| |
| − | ![[Levels_of_Evidence#Evidence|Evidence]]
| |
| − | |-
| |
| − | |[https://onlinelibrary.wiley.com/doi/10.1111/j.1365-2141.2010.08235.x/full Grövdal et al. 2010]
| |
| − | | style="background-color:#91cf61" |Phase II
| |
| − | |-
| |
| − | |}
| |
| − | ''Intended to be used for transformed MDS patients in remission after AML induction therapy.''
| |
| − | ====Preceding treatment====
| |
| − | *7+2d
| |
| − | ====Chemotherapy====
| |
| − | *[[Azacitidine (Vidaza)]] 60 mg/m<sup>2</sup> SC once per day 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. Epub 2010 May 20. [https://onlinelibrary.wiley.com/doi/10.1111/j.1365-2141.2010.08235.x/full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/20497178 PubMed]
| |
| − | | |
| − | ==Decitabine monotherapy {{#subobject:d8250a|Regimen=1}}==
| |
| − | {| class="wikitable" style="float:right; margin-left: 5px;"
| |
| − | |-
| |
| − | |[[#top|back to top]]
| |
| − | |}
| |
| − | | |
| − | ===Regimen {{#subobject:4726aa|Variant=1}}===
| |
| − | {| class="wikitable" style="width: 100%; text-align:center;"
| |
| − | !Study
| |
| − | ![[Levels_of_Evidence#Evidence|Evidence]]
| |
| − | |-
| |
| − | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2867720/ Blum et al. 2010]
| |
| − | | style="background-color:#91cf61" |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.''
| |
| − | ====Preceding treatment====
| |
| − | *[[#Decitabine_monotherapy|Decitabine induction]]
| |
| − | ====Chemotherapy====
| |
| − | *[[Decitabine (Dacogen)]] 20 mg/m<sup>2</sup> IV over 60 minutes 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 less than 500/uL) persisting greater than or equal to 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'''
| |
| − | | |
| − | ===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. Epub 2010 Apr 5. [http://www.pnas.org/content/107/16/7473.full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2867720/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/20368434 PubMed]
| |
| − | | |
| − | ==LoDAC {{#subobject:4c65c8|Regimen=1}}==
| |
| − | {| class="wikitable" style="float:right; margin-left: 5px;"
| |
| − | |-
| |
| − | |[[#top|back to top]]
| |
| − | |}
| |
| − | LoDAC: '''<u>Lo</u>'''w '''<u>D</u>'''ose '''<u>A</u>'''ra-'''<u>C</u>''' (cytarabine)
| |
| − | <br>LDAC: '''<u>L</u>'''ow '''<u>D</u>'''ose '''<u>A</u>'''ra-'''<u>C</u>''' (cytarabine)
| |
| − | | |
| − | ===Regimen {{#subobject:2f5aa0|Variant=1}}===
| |
| − | {| class="wikitable" style="width: 100%; text-align:center;"
| |
| − | !Study
| |
| − | ![[Levels_of_Evidence#Evidence|Evidence]]
| |
| − | !Comparator
| |
| − | ![[Levels_of_Evidence#Efficacy|Efficacy]]
| |
| − | |-
| |
| − | |[https://www.nature.com/articles/2401850 Robles et al. 2000 (ECOG E5483)]
| |
| − | | style="background-color:#1a9851" |Phase III (E)
| |
| − | |[[#Observation|Observation]]
| |
| − | | style="background-color:#d9ef8b" |Might have superior DFS
| |
| − | |-
| |
| − | |}
| |
| − | ====Preceding treatment====
| |
| − | *HiDAC, then amsacrine induction
| |
| − | ====Chemotherapy====
| |
| − | *[[Cytarabine (Cytosar)]] 10 mg/m<sup>2</sup> SC BID on days 1 to 21
| |
| − | | |
| − | '''8-week cycles'''
| |
| − | | |
| − | ===References===
| |
| − | # '''ECOG E5483:''' 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. [https://www.nature.com/articles/2401850 link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/10942228 PubMed]
| |
| − | | |
| − | ==Observation==
| |
| − | {| class="wikitable" style="float:right; margin-left: 5px;"
| |
| − | |-
| |
| − | |[[#top|back to top]]
| |
| − | |}
| |
| − | | |
| − | ===Regimen===
| |
| − | {| class="wikitable" style="width: 100%; text-align:center;"
| |
| − | !Study
| |
| − | ![[Levels_of_Evidence#Evidence|Evidence]]
| |
| − | !Comparator
| |
| − | ![[Levels_of_Evidence#Efficacy|Efficacy]]
| |
| − | |-
| |
| − | |[https://www.nature.com/articles/2401850 Robles et al. 2000 (ECOG E5483)]
| |
| − | | style="background-color:#1a9851" |Phase III (C)
| |
| − | |[[#LoDAC_2|LoDAC]]
| |
| − | | style="background-color:#fee08b" |Might have inferior DFS
| |
| − | |-
| |
| − | |}
| |
| − | ''No further antineoplastic treatment; included here because it was used as a comparator arm in this setting.''
| |
| − | ====Preceding treatment====
| |
| − | *HiDAC, then amsacrine induction
| |
| − | ===References===
| |
| − | # '''ECOG E5483:''' 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. [https://www.nature.com/articles/2401850 link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/10942228 PubMed]
| |
| − | | |
| − | ==Panobinostat monotherapy {{#subobject:ce9c31|Regimen=1}}==
| |
| − | {| class="wikitable" style="float:right; margin-left: 5px;"
| |
| − | |-
| |
| − | |[[#top|back to top]]
| |
| − | |}
| |
| − | ===Regimen {{#subobject:f4cc4b|Variant=1}}===
| |
| − | {| class="wikitable" style="width: 100%; text-align:center;"
| |
| − | !Study
| |
| − | ![[Levels_of_Evidence#Evidence|Evidence]]
| |
| − | |-
| |
| − | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4591761/ Ocio et al. 2015 (panobidara)]
| |
| − | | style="background-color:#91cf61" |Phase Ib/II
| |
| − | |-
| |
| − | |}
| |
| − | ''The panobinostat dose is the MTD in this phase Ib/II study.''
| |
| − | ====Preceding treatment====
| |
| − | *[[#7.2B3i_.26_Panobinostat|7+3i & Panobinostat]] x 2 to 3 cycles
| |
| − | ====Chemotherapy====
| |
| − | *[[Panobinostat (Farydak)]] as follows:
| |
| − | **Odd weeks: 40 mg PO once per day three days of the week
| |
| − | **Even weeks: no treatment
| |
| | | | |
| − | '''Continued indefinitely'''
| + | =Maintenance after upfront therapy= |
| − | | + | ==Midostaurin monotherapy {{#subobject:e0bb17|Regimen=1}}== |
| − | ===References=== | + | {{#subobject:9fe269|Variant=1}} |
| − | # Ocio EM, Herrera P, Olave MT, Castro N, Pérez-Simón JA, Brunet S, Oriol A, Mateo M, Sanz MÁ, López J, Montesinos P, Chillón MC, Prieto-Conde MI, Díez-Campelo M, González M, Vidriales MB, Mateos MV, San Miguel JF; PETHEMA Group. Panobinostat as part of induction and maintenance for elderly patients with newly diagnosed acute myeloid leukemia: phase Ib/II panobidara study. Haematologica. 2015 Oct;100(10):1294-300. Epub 2015 Jul 9. [http://www.haematologica.org/content/100/10/1294 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4591761/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/26160880 PubMed]
| + | {{:Midostaurin (Rydapt) maintenance therapy for acute myeloid leukemia (AML)}} |
| | | | |
| | ==Sorafenib monotherapy {{#subobject:23822e|Regimen=1}}== | | ==Sorafenib monotherapy {{#subobject:23822e|Regimen=1}}== |
| Line 2,567: |
Line 92: |
| | |[[#top|back to top]] | | |[[#top|back to top]] |
| | |} | | |} |
| − |
| |
| | ===Regimen {{#subobject:b50325|Variant=1}}=== | | ===Regimen {{#subobject:b50325|Variant=1}}=== |
| | {| class="wikitable" style="width: 100%; text-align:center;" | | {| class="wikitable" style="width: 100%; text-align:center;" |
| Line 2,573: |
Line 97: |
| | ![[Levels_of_Evidence#Evidence|Evidence]] | | ![[Levels_of_Evidence#Evidence|Evidence]] |
| | |- | | |- |
| − | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2930809/ Ravandi et al. 2010] | + | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5637402/ Uy et al. 2017 (CALGB 11001)] |
| − | | style="background-color:#91cf61" |Phase I/II | + | | style="background-color:#91cf61" |Phase II |
| | |- | | |- |
| | |} | | |} |
| | ====Preceding treatment==== | | ====Preceding treatment==== |
| − | *[[#Cytarabine.2C_Idarubicin.2C_Sorafenib|Cytarabine, Idarubicin, Sorafenib consolidation]] | + | *[[#IDAC_.26_Sorafenib|IDAC & Sorafenib consolidation]] |
| | ====Chemotherapy==== | | ====Chemotherapy==== |
| | *[[Sorafenib (Nexavar)]] 400 mg PO BID | | *[[Sorafenib (Nexavar)]] 400 mg PO BID |
| − |
| |
| − | '''Up to one year of sorafenib therapy, including consolidation course(s)'''
| |
| − |
| |
| − | ===References===
| |
| − | <!-- no pre-pub disclosed -->
| |
| − | # 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. Epub 2010 Mar 8. [http://jco.ascopubs.org/content/28/11/1856.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2930809/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/20212254 PubMed]
| |
| − | ## '''Update:''' Ravandi F, Arana Yi C, Cortes JE, Levis M, Faderl S, Garcia-Manero G, Jabbour E, Konopleva M, O'Brien S, Estrov Z, Borthakur G, Thomas D, Pierce S, Brandt M, Pratz K, Luthra R, Andreeff M, Kantarjian H. Final report of phase II study of sorafenib, cytarabine and idarubicin for initial therapy in younger patients with acute myeloid leukemia. Leukemia. 2014 Jul;28(7):1543-5. Epub 2014 Feb 3. [https://www.nature.com/leu/journal/v28/n7/full/leu201454a.html link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4091714/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/24487412 PubMed]
| |
| − |
| |
| − | ==Vorinostat monotherapy {{#subobject:df4c1|Regimen=1}}==
| |
| − | {| class="wikitable" style="float:right; margin-left: 5px;"
| |
| − | |-
| |
| − | |[[#top|back to top]]
| |
| − | |}
| |
| − |
| |
| − | ===Regimen {{#subobject:bb31d1|Variant=1}}===
| |
| − | {| class="wikitable" style="width: 100%; text-align:center;"
| |
| − | !Study
| |
| − | ![[Levels_of_Evidence#Evidence|Evidence]]
| |
| − | |-
| |
| − | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4879705/ Garcia-Manero et al. 2012]
| |
| − | | style="background-color:#91cf61" |Phase II
| |
| − | |-
| |
| − | |}
| |
| − | ====Preceding treatment====
| |
| − | *[[#Cytarabine.2C_Idarubicin.2C_Vorinostat|Cytarabine, Idarubicin, Vorinostat consolidation]]
| |
| − | ====Chemotherapy====
| |
| − | *[[Vorinostat (Zolinza)]] 200 mg PO TID on days 1 to 14
| |
| | | | |
| | '''28-day cycle for up to 12 cycles''' | | '''28-day cycle for up to 12 cycles''' |
| | | | |
| | ===References=== | | ===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. [http://jco.ascopubs.org/content/30/18/2204.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4879705/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/22585696 PubMed] | + | # '''CALGB 11001:''' Uy GL, Mandrekar SJ, Laumann K, Marcucci G, Zhao W, Levis MJ, Klepin HD, Baer MR, Powell BL, Westervelt P, DeAngelo DJ, Stock W, Sanford B, Blum WG, Bloomfield CD, Stone RM, Larson RA. A phase 2 study incorporating sorafenib into the chemotherapy for older adults with FLT3-mutated acute myeloid leukemia: CALGB 11001. Blood Adv. 2017 Jan 24;1(5):331-340. [http://www.bloodadvances.org/content/1/5/331 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5637402/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/29034366 PubMed] |
| | | | |
| | =Relapsed or refractory, salvage therapy= | | =Relapsed or refractory, salvage therapy= |
| − | ''Note: these are generally aggressive regimens intended to induce a second remission as part of a path towards pre-planned allogeneic HSCT.''
| + | ==Midostaurin monotherapy {{#subobject:badb27|Regimen=1}}== |
| − | ==5+2d {{#subobject:df9bab|Regimen=1}}== | |
| | {| class="wikitable" style="float:right; margin-left: 5px;" | | {| class="wikitable" style="float:right; margin-left: 5px;" |
| | |- | | |- |
| | |[[#top|back to top]] | | |[[#top|back to top]] |
| | |} | | |} |
| − | ===Regimen {{#subobject:c9d569|Variant=1}}=== | + | ===Variant #1 {{#subobject:170b53|Variant=1}}=== |
| − | {| class="wikitable" style="width: 100%; text-align:center;"
| |
| − | !Study
| |
| − | ![[Levels_of_Evidence#Evidence|Evidence]]
| |
| − | |-
| |
| − | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4800702/ Zeidner et al. 2015]
| |
| − | | style="background-color:#91cf61" |Non-randomized
| |
| − | |-
| |
| − | |}
| |
| − | ====Preceding treatment====
| |
| − | *[[#7.2B3d_.28high-dose.29|7+3d (high-dose)]]
| |
| − | | |
| − | ====Chemotherapy====
| |
| − | *[[Cytarabine (Cytosar)]] 100 mg/m<sup>2</sup>/day IV continuous infusion on days 1 to 5 (total dose: 500 mg/m<sup>2</sup>)
| |
| − | *[[Daunorubicin (Cerubidine)]] 45 mg/m<sup>2</sup> IV once per day on days 1 & 2
| |
| − | | |
| − | '''5-day course'''
| |
| − | | |
| − | ===References===
| |
| − | # Zeidner JF, Foster MC, Blackford AL, Litzow MR, Morris LE, Strickland SA, Lancet JE, Bose P, Levy MY, Tibes R, Gojo I, Gocke CD, Rosner GL, Little RF, Wright JJ, Doyle LA, Smith BD, Karp JE. Randomized multicenter phase II study of flavopiridol (alvocidib), cytarabine, and mitoxantrone (FLAM) versus cytarabine/daunorubicin (7+3) in newly diagnosed acute myeloid leukemia. Haematologica. 2015 Sep;100(9):1172-9. Epub 2015 May 28. [http://www.haematologica.org/content/100/9/1172 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4800702/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/26022709 PubMed]
| |
| − | | |
| − | ==ADE (standard-dose Ara-C) {{#subobject:d16134|Regimen=1}}==
| |
| − | {| class="wikitable" style="float:right; margin-left: 5px;"
| |
| − | |-
| |
| − | |[[#top|back to top]]
| |
| − | |}
| |
| − | ADE: '''<u>A</u>'''ra-C (Cytarabine), '''<u>D</u>'''aunorubicin, '''<u>E</u>'''toposide
| |
| − | | |
| − | ===Regimen {{#subobject:a99e51|Variant=1}}===
| |
| | {| class="wikitable" style="width: 100%; text-align:center;" | | {| class="wikitable" style="width: 100%; text-align:center;" |
| | !Study | | !Study |
| | ![[Levels_of_Evidence#Evidence|Evidence]] | | ![[Levels_of_Evidence#Evidence|Evidence]] |
| | !Comparator | | !Comparator |
| − | ![[Levels_of_Evidence#Efficacy|Efficacy]]
| |
| − | |-
| |
| − | |[http://www.bloodjournal.org/content/107/12/4614.long Milligan et al. 2006 (MRC AML-HR)]
| |
| − | | style="background-color:#1a9851" |Phase III (C)
| |
| − | |FLA
| |
| − | | style="background-color:#91cf60" |Seems to have superior OS
| |
| − | |-
| |
| − | |}
| |
| − |
| |
| − | ====Chemotherapy, Course 1====
| |
| − | *[[Cytarabine (Cytosar)]] 100 mg/m<sup>2</sup> IV push Q12H on days 1 to 10 (20 total doses)
| |
| − | *[[Daunorubicin (Cerubidine)]] 50 mg/m<sup>2</sup> IV slow push once per day on days 1, 3, 5
| |
| − | *[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1 to 5
| |
| − |
| |
| − | ====Chemotherapy, Course 2====
| |
| − | *[[Cytarabine (Cytosar)]] 100 mg/m<sup>2</sup> IV push Q12H on days 1 to 8 (16 total doses)
| |
| − | *[[Daunorubicin (Cerubidine)]] 50 mg/m<sup>2</sup> IV slow push once per day on days 1, 3, 5
| |
| − | *[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1 to 5
| |
| − |
| |
| − | ===References===
| |
| − | # '''MRC AML-HR:''' 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. [http://www.bloodjournal.org/content/107/12/4614.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/16484584 PubMed]
| |
| − |
| |
| − | ==Cladribine monotherapy {{#subobject:b80308|Regimen=1}}==
| |
| − | {| class="wikitable" style="float:right; margin-left: 5px;"
| |
| − | |-
| |
| − | |[[#top|back to top]]
| |
| − | |}
| |
| − | ===Regimen {{#subobject:d51fc2|Variant=1}}===
| |
| − | {| class="wikitable" style="width: 100%; text-align:center;"
| |
| − | !Study
| |
| − | ![[Levels_of_Evidence#Evidence|Evidence]]
| |
| | |- | | |- |
| − | |[http://jco.ascopubs.org/content/10/3/364.abstract Santana et al. 1992] | + | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4135183/ Fischer et al. 2010] |
| − | | style="background-color:#91cf61" |Phase II | + | | style="background-color:#1a9851" |Randomized Phase IIB (E) |
| | + | |Midostaurin 100 mg BID |
| | |- | | |- |
| | |} | | |} |
| | ====Chemotherapy==== | | ====Chemotherapy==== |
| − | *[[Cladribine (Leustatin)]] 8.9 mg/m<sup>2</sup>/day IV continuous infusion on days 1 to 5 (total dose: 44.5 mg/m<sup>2</sup>) | + | *[[Midostaurin (Rydapt)]] 50 mg PO BID |
| | | | |
| − | ===References===
| + | '''Continued indefinitely''' |
| − | # 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. [http://jco.ascopubs.org/content/10/3/364.abstract link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/1346800 PubMed]
| |
| − | | |
| − | ==CLAG {{#subobject:702383|Regimen=1}}==
| |
| − | {| class="wikitable" style="float:right; margin-left: 5px;"
| |
| − | |-
| |
| − | |[[#top|back to top]]
| |
| − | |}
| |
| − | CLAG: '''<u>CL</u>'''adribine, '''<u>A</u>'''ra-C (Cytarabine), '''<u>G</u>'''-CSF
| |
| − | | |
| − | ===Regimen {{#subobject:12d1bb|Variant=1}}===
| |
| − | {| class="wikitable" style="width: 100%; text-align:center;"
| |
| − | !Study
| |
| − | ![[Levels_of_Evidence#Evidence|Evidence]]
| |
| − | |-
| |
| − | |[https://www.tandfonline.com/doi/full/10.3109/10428190009053545 Robak et al. 2000]
| |
| − | | style="background-color:#91cf61" |Phase II
| |
| − | |-
| |
| − | |}
| |
| − | ====Chemotherapy====
| |
| − | *[[Cladribine (Leustatin)]] 5 mg/m<sup>2</sup> IV over 2 hours once per day on days 1 to 5, '''given first'''
| |
| − | *[[Cytarabine (Cytosar)]] 2000 mg/m<sup>2</sup> IV over 4 hours once per day on days 1 to 5, '''given second, 2 hours after [[Cladribine (Leustatin)]]'''
| |
| − | *[[Filgrastim (Neupogen)]] 300 mcg SC once per day on days -1 to 5; first dose is given 24 hours before first dose of [[Cladribine (Leustatin)]]
| |
| − | | |
| − | ===References===
| |
| − | # Robak T, Wrzesień-Kuś A, Lech-Marańda E, Kowal M, Dmoszyńska 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. [https://www.tandfonline.com/doi/full/10.3109/10428190009053545 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/10975390 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. [https://www.ncbi.nlm.nih.gov/pubmed/19717379 PubMed]
| |
| − | | |
| − | ==CLAG-M {{#subobject:51b417|Regimen=1}}==
| |
| − | {| class="wikitable" style="float:right; margin-left: 5px;"
| |
| − | |-
| |
| − | |[[#top|back to top]]
| |
| − | |}
| |
| − | CLAG-M: '''<u>CL</u>'''adribine, '''<u>A</u>'''ra-C (Cytarabine), '''<u>G</u>'''-CSF, '''<u>M</u>'''itoxantrone
| |
| − | ===Regimen {{#subobject:e0b308|Variant=1}}===
| |
| − | {| class="wikitable" style="width: 100%; text-align:center;"
| |
| − | !Study
| |
| − | ![[Levels_of_Evidence#Evidence|Evidence]]
| |
| − | |-
| |
| − | |[https://onlinelibrary.wiley.com/doi/10.1111/j.1600-0609.2007.00988.x/abstract Wierzbowksa et al. 2007]
| |
| − | | style="background-color:#91cf61" |Phase II
| |
| − | |-
| |
| − | |}
| |
| − | ====Chemotherapy====
| |
| − | *[[Cladribine (Leustatin)]] 5 mg/m<sup>2</sup> IV over 2 hours once per day on days 1 to 5, '''given first'''
| |
| − | *[[Cytarabine (Cytosar)]] 2000 mg/m<sup>2</sup> IV over 4 hours once per day on days 1 to 5, '''given second, 2 hours after cladribine'''
| |
| − | *[[Filgrastim (Neupogen)]] based on WBC count:
| |
| − | **WBC count less than or equal to 20 x 10<sup>9</sup>/L: 300 mcg SC once per day on days 0 to 5; '''first dose is given 24 hours prior to chemotherapy'''
| |
| − | **WBC count greater than 20 x 10<sup>9</sup>/L: 300 mcg SC once per day on days 1 to 5, '''commenced simultaneously to cladribine'''
| |
| − | *[[Mitoxantrone (Novantrone)]] 10 mg/m<sup>2</sup> IV once per day on days 1 to 3
| |
| | | | |
| − | '''One course'''
| + | ===Variant #2 {{#subobject:2dfbf4|Variant=1}}=== |
| − | ====Subsequent treatment====
| |
| − | *Patients with PR were recommended to undergo a second course of CLAG-M.
| |
| − | **Primary refractory patients achieving CR after 2nd CLAG-M: [[#HAM|HAM consolidation]]
| |
| − | *Others could receive another course of CLAG-M or [[#HAM|HAM consolidation]] per investigator discretion
| |
| − | | |
| − | ===References===
| |
| − | # Wierzbowska A, Robak T, Pluta A, Wawrzyniak E, Cebula B, Holowiecki J, Kyrcz-Krzemien S, Grosicki S, Giebel S, Skotnicki AB, Piatkowska-Jakubas B, Kuliczkowski K, Kielbinski M, Zawilska K, Kloczko 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. [https://onlinelibrary.wiley.com/doi/10.1111/j.1600-0609.2007.00988.x/abstract link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/18076637 PubMed] content property of [http://hemonc.org 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. [https://www.ncbi.nlm.nih.gov/pubmed/19717379 PubMed]
| |
| − | | |
| − | ==CLARA {{#subobject:48978a|Regimen=1}}==
| |
| − | {| class="wikitable" style="float:right; margin-left: 5px;"
| |
| − | |-
| |
| − | |[[#top|back to top]]
| |
| − | |}
| |
| − | CLARA: '''<u>CL</u>'''ofarabine and '''<u>ARA</u>'''-C (Cytarabine)
| |
| − | <br>GCLAC: '''<u>G</u>'''-CSF, '''<u>C</u>'''lofarabine, '''<u>A</u>'''ra-'''<u>C</u>''' (Cytarabine)
| |
| − | ===Regimen {{#subobject:b8a3a2|Variant=1}}===
| |
| − | {| class="wikitable" style="width: 100%; text-align:center;"
| |
| − | !Study
| |
| − | ![[Levels_of_Evidence#Evidence|Evidence]]
| |
| − | |-
| |
| − | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4834701/ Becker et al. 2011]
| |
| − | | style="background-color:#91cf61" |Phase II
| |
| − | |-
| |
| − | |}
| |
| − | ====Chemotherapy====
| |
| − | *[[Clofarabine (Clolar)]] 25 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1 to 5, given first
| |
| − | *[[Cytarabine (Cytosar)]] 2000 mg/m<sup>2</sup> IV over 4 hours once per day on days 1 to 5, given second, 4 hours after start of [[Clofarabine (Clolar)]] infusion
| |
| − | *[[Filgrastim (Neupogen)]] 5 mcg/kg SC once per day starting day -1, continuing until ANC at least 2000/uL for 2 consecutive days
| |
| − | | |
| − | '''One course with one re-induction allowed for patients with greater than 5% blasts at day 21'''
| |
| − | ====Subsequent treatment====
| |
| − | *Patients achieving CR could receive consolidation with clofarabine reduced to 20 mg/m2, and cytarabine reduced to 1000 mg/m2, up to 2 cycles
| |
| − | | |
| − | ===References===
| |
| − | # Becker PS, Kantarjian HM, Appelbaum FR, Petersdorf SH, Storer B, Pierce S, Shan J, Hendrie PC, Pagel JM, Shustov AR, Stirewalt DL, Faderl S, Harrington E, Estey EH. Clofarabine with high dose cytarabine and granulocyte colony-stimulating factor (G-CSF) priming for relapsed and refractory acute myeloid leukaemia. Br J Haematol. 2011 Oct;155(2):182-9. Epub 2011 Aug 18. [https://onlinelibrary.wiley.com/doi/10.1111/j.1365-2141.2011.08831.x/full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4834701/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/21848522 PubMed]
| |
| − | | |
| − | ==Clofarabine monotherapy {{#subobject:54a7a0|Regimen=1}}==
| |
| − | {| class="wikitable" style="float:right; margin-left: 5px;"
| |
| − | |-
| |
| − | |[[#top|back to top]]
| |
| − | |}
| |
| − | ===Regimen {{#subobject:dafe74|Variant=1}}===
| |
| − | {| class="wikitable" style="width: 100%; text-align:center;"
| |
| − | !Study
| |
| − | ![[Levels_of_Evidence#Evidence|Evidence]]
| |
| − | |-
| |
| − | |[http://www.bloodjournal.org/content/102/7/2379.long Kantarjian et al. 2003]
| |
| − | | style="background-color:#91cf61" |Phase II
| |
| − | |-
| |
| − | |}
| |
| − | ====Chemotherapy====
| |
| − | *[[Clofarabine (Clolar)]] 40 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1 to 5
| |
| − | | |
| − | '''3- to 6-week cycles'''
| |
| − | | |
| − | ===References===
| |
| − | # Kantarjian H, Gandhi V, Cortes J, Verstovsek S, Du M, Garcia-Manero G, Giles F, Faderl S, O'Brien S, Jeha S, Davis J, Shaked Z, Craig A, Keating M, Plunkett W, Freireich EJ. Phase 2 clinical and pharmacologic study of clofarabine in patients with refractory or relapsed acute leukemia. Blood. 2003 Oct 1;102(7):2379-86. Epub 2003 Jun 5. [http://www.bloodjournal.org/content/102/7/2379.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/12791647 PubMed]
| |
| − | | |
| − | ==Clofarabine & Cytarabine {{#subobject:23e3f2|Regimen=1}}==
| |
| − | {| class="wikitable" style="float:right; margin-left: 5px;"
| |
| − | |-
| |
| − | |[[#top|back to top]]
| |
| − | |}
| |
| − | ===Variant #1, 30/1000 {{#subobject:f6ada8|Variant=1}}===
| |
| − | {| class="wikitable" style="width: 100%; text-align:center;"
| |
| − | !Study
| |
| − | ![[Levels_of_Evidence#Evidence|Evidence]]
| |
| − | |-
| |
| − | |[https://www.nature.com/leu/journal/v30/n2/full/leu2015226a.html Middeke et al. 2015 (BRIDGE)]
| |
| − | | style="background-color:#91cf61" |Phase II
| |
| − | |-
| |
| − | |}
| |
| − | ====Chemotherapy====
| |
| − | *[[Clofarabine (Clolar)]] 30 mg/m<sup>2</sup> IV once per day on days 1 to 5
| |
| − | *[[Cytarabine (Cytosar)]] 1000 mg/m<sup>2</sup> IV once per day on days 1 to 5
| |
| − | | |
| − | '''At least one cycle'''
| |
| − | ====Subsequent treatment====
| |
| − | *Chemo-responsive patients: [[Transplant_conditioning_regimens#Clofarabine_.26_Melphalan|Clofarabine & melphalan, then allogeneic HSCT]]
| |
| − | | |
| − | ===Variant #2, 40/1000 {{#subobject:d95457|Variant=1}}=== | |
| | {| class="wikitable" style="width: 100%; text-align:center;" | | {| class="wikitable" style="width: 100%; text-align:center;" |
| | !Study | | !Study |
| | ![[Levels_of_Evidence#Evidence|Evidence]] | | ![[Levels_of_Evidence#Evidence|Evidence]] |
| | !Comparator | | !Comparator |
| − | ![[Levels_of_Evidence#Efficacy|Efficacy]]
| |
| | |- | | |- |
| − | |[http://www.bloodjournal.org/content/105/3/940.long Faderl et al. 2004]
| + | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4135183/ Fischer et al. 2010] |
| − | | style="background-color:#91cf61" |Phase I/II
| + | | style="background-color:#1a9851" |Randomized Phase IIB (E) |
| − | | style="background-color:#d3d3d3" |
| + | |Midostaurin 50 mg BID |
| − | | style="background-color:#d3d3d3" |
| |
| − | |-
| |
| − | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3228084/ Agura et al. 2011] | |
| − | | style="background-color:#91cf61" |Phase II
| |
| − | | style="background-color:#d3d3d3" |
| |
| − | | style="background-color:#d3d3d3" |
| |
| − | |-
| |
| − | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4874149/ Faderl et al. 2012 (CLASSIC I)]
| |
| − | | style="background-color:#1a9851" |Phase III (E) | |
| − | |[[#Cytarabine_monotherapy_2|Cytarabine]] | |
| − | | style="background-color:#1a9850" |Superior EFS
| |
| | |- | | |- |
| | |} | | |} |
| | ====Chemotherapy==== | | ====Chemotherapy==== |
| − | *[[Clofarabine (Clolar)]] 40 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1 to 5, '''given first''' | + | *[[Midostaurin (Rydapt)]] 100 mg PO BID |
| − | **Note: in Faderl et al. 2004, clofarabine was given on days 2 to 6
| |
| − | *[[Cytarabine (Cytosar)]] 1000 mg/m<sup>2</sup> IV over 2 hours once per day on days 1 to 5, '''given second, 3 to 4 hours after completion of clofarabine infusion'''
| |
| | | | |
| − | ====Supportive medications====
| + | '''Continued indefinitely''' |
| − | *Best described in Agura et al. 2011
| |
| − | *[[Dexamethasone (Decadron)]] 10 mg IV once per day
| |
| − | *[[:Category:Serotonin_5-HT3_antagonists|5-HT3 antagonists]] on each day of chemotherapy
| |
| − | *Hydration at 150 mL/m<sup>2</sup>/H "to prevent tumor lysis syndrome" during chemotherapy
| |
| − | *[[Bumetanide (Bumex)]] 2 to 4 mg IV push once to twice per day as needed to keep weight within 1 kg of patient's initial weight
| |
| − | *[[Levofloxacin (Levaquin)]] 500 mg PO/IV once per day
| |
| − | *[[Acyclovir (Zovirax)]] 500 mg IV Q12H
| |
| − | *One of the following antifungals:
| |
| − | **[[Caspofungin (Cancidas)]] 50 mg IV once per day
| |
| − | **[[Voriconazole (Vfend)]] 200 mg (route not specified) BID
| |
| − | *Parenteral nutrition allowed
| |
| − | *No routine use of growth factors
| |
| − | '''1 to 4 cycles''' | |
| − | ====Subsequent treatment====
| |
| − | *See individual papers for details
| |
| | | | |
| − | ===Variant #3, Clofarabine & LDAC {{#subobject:d4a73c|Variant=1}}=== | + | ===Variant #3 {{#subobject:c52466|Variant=1}}=== |
| | {| class="wikitable" style="width: 100%; text-align:center;" | | {| class="wikitable" style="width: 100%; text-align:center;" |
| | !Study | | !Study |
| | ![[Levels_of_Evidence#Evidence|Evidence]] | | ![[Levels_of_Evidence#Evidence|Evidence]] |
| | |- | | |- |
| − | |[https://onlinelibrary.wiley.com/doi/10.1111/bjh.13437/full Buckley et al. 2015] | + | |[http://www.bloodjournal.org/content/105/1/54.long Stone et al. 2004] |
| − | | style="background-color:#91cf61" |Phase I/II
| |
| − | |-
| |
| − | |}
| |
| − | LDAC: '''<u>L</u>'''ow-'''<u>D</u>'''ose '''<u>A</u>'''ra-'''<u>C</u>''' (Cytarabine)
| |
| − | | |
| − | ''The dose of clofarabine is the one reported as the MTD. Note that the doses of both drugs are much lower than the other variants here.''
| |
| − | ====Chemotherapy====
| |
| − | *[[Clofarabine (Clolar)]] 20 mg PO once per day on days 1 to 5
| |
| − | *[[Cytarabine (Cytosar)]] as follows (per physician choice):
| |
| − | **20 mg/m<sup>2</sup> SC BID on days 1 to 10
| |
| − | **20 mg/m<sup>2</sup> SC once per day on days 1 to 14
| |
| − | | |
| − | '''Cycle duration not explicitly defined; presumably 28 days'''
| |
| − | | |
| − | ===References===
| |
| − | # Faderl S, Gandhi V, O'Brien S, Bonate P, Cortes J, Estey E, Beran M, Wierda W, Garcia-Manero G, Ferrajoli A, Estrov Z, Giles FJ, Du M, Kwari M, Keating M, Plunkett W, Kantarjian H. Results of a phase 1-2 study of clofarabine in combination with cytarabine (ara-C) in relapsed and refractory acute leukemias. Blood. 2005 Feb 1;105(3):940-7. Epub 2004 Oct 14. [http://www.bloodjournal.org/content/105/3/940.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/15486072 PubMed]
| |
| − | # 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. Epub 2011 Jan 27. [http://theoncologist.alphamedpress.org/content/16/2/197.full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3228084/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/21273514 PubMed]
| |
| − | <!-- Presented in part at the 53rd Annual Meeting of the American Society of Clinical Oncology, Chicago, IL, June 3-7, 2011, and at the 16th Congress of the European Hematology Association, London, United Kingdom, June 9-12, 2011. -->
| |
| − | # '''CLASSIC I:''' 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. Epub 2012 May 14. [http://jco.ascopubs.org/content/30/20/2492.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4874149/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/22585697 PubMed]
| |
| − | # Buckley SA, Mawad R, Gooley TA, Becker PS, Sandhu V, Hendrie P, Scott BL, Wood BL, Walter RB, Smith K, Dean C, Estey EH, Pagel JM. A phase I/II study of oral clofarabine plus low-dose cytarabine in previously treated acute myeloid leukaemia and high-risk myelodysplastic syndrome patients at least 60 years of age. Br J Haematol. 2015 Aug;170(3):349-55. Epub 2015 Apr 8. [https://onlinelibrary.wiley.com/doi/10.1111/bjh.13437/full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/25854284 PubMed]
| |
| − | # '''BRIDGE:''' Middeke JM, Herbst R, Parmentier S, Bug G, Hänel M, Stuhler G, Schäfer-Eckart K, Rösler W, Klein S, Bethge W, Bitz U, Büttner B, Knoth H, Alakel N, Schaich M, Morgner A, Kramer M, Sockel K, von Bonin M, Stölzel F, Platzbecker U, Röllig C, Thiede C, Ehninger G, Bornhäuser M, Schetelig J. Clofarabine salvage therapy before allogeneic hematopoietic stem cell transplantation in patients with relapsed or refractory AML: results of the BRIDGE trial. Leukemia. 2016 Feb;30(2):261-7. Epub 2015 Aug 18. [https://www.nature.com/leu/journal/v30/n2/full/leu2015226a.html link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/26283567 PubMed]
| |
| − | | |
| − | ==Cytarabine monotherapy {{#subobject:b8c40b|Regimen=1}}==
| |
| − | {| class="wikitable" style="float:right; margin-left: 5px;"
| |
| − | |-
| |
| − | |[[#top|back to top]]
| |
| − | |}
| |
| − | ===Regimen {{#subobject:edda3b|Variant=1}}===
| |
| − | {| class="wikitable" style="width: 100%; text-align:center;"
| |
| − | !Study
| |
| − | ![[Levels_of_Evidence#Evidence|Evidence]]
| |
| − | !Comparator
| |
| − | ![[Levels_of_Evidence#Efficacy|Efficacy]]
| |
| − | |-
| |
| − | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4874149/ Faderl, et al. 2012 (CLASSIC I)]
| |
| − | | style="background-color:#1a9851" |Phase III (C)
| |
| − | |[[#Clofarabine_.26_Cytarabine|Clofarabine & Cytarabine]]
| |
| − | | style="background-color:#d73027" |Inferior EFS
| |
| − | |-
| |
| − | |[https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(15)00201-6/fulltext Ravandi et al. 2015 (VALOR)]
| |
| − | | style="background-color:#1a9851" |Phase III (C)
| |
| − | |Cytarabine & Vosaroxin
| |
| − | | style="background-color:#fee08b" |Might have inferior OS
| |
| − | |-
| |
| − | |}
| |
| − | ''Note: In '''CLASSIC I''', 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." In '''VALOR''', the total duration of treatment is not specified.''
| |
| − | ====Chemotherapy====
| |
| − | *[[Cytarabine (Cytosar)]] 1000 mg/m<sup>2</sup> IV over 2 hours once per day on days 1 to 5
| |
| − | | |
| − | ====Supportive medications====
| |
| − | *"The use of prophylactic antibacterial, antifungal, and antiviral agents was recommended according to institutional guidelines."
| |
| − | | |
| − | '''1 to 3 cycles (see note)'''
| |
| − | | |
| − | ===References===
| |
| − | <!-- Presented in part at the 53rd Annual Meeting of the American Society of Clinical Oncology, Chicago, IL, June 3-7, 2011, and at the 16th Congress of the European Hematology Association, London, United Kingdom, June 9-12, 2011. -->
| |
| − | # 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. Epub 2012 May 14. [http://jco.ascopubs.org/content/30/20/2492.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4874149/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/22585697 PubMed]
| |
| − | # Ravandi F, Ritchie EK, Sayar H, Lancet JE, Craig MD, Vey N, Strickland SA, Schiller GJ, Jabbour E, Erba HP, Pigneux A, Horst HA, Recher C, Klimek VM, Cortes J, Roboz GJ, Odenike O, Thomas X, Havelange V, Maertens J, Derigs HG, Heuser M, Damon L, Powell BL, Gaidano G, Carella AM, Wei A, Hogge D, Craig AR, Fox JA, Ward R, Smith JA, Acton G, Mehta C, Stuart RK, Kantarjian HM. Vosaroxin plus cytarabine versus placebo plus cytarabine in patients with first relapsed or refractory acute myeloid leukaemia (VALOR): a randomised, controlled, double-blind, multinational, phase 3 study. Lancet Oncol. 2015 Sep;16(9):1025-36. Epub 2015 Jul 30.[https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(15)00201-6/fulltext link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4822512/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/26234174 PubMed]
| |
| − | | |
| − | ==Cytarabine & Mitoxantrone {{#subobject:fba448|Regimen=1}}==
| |
| − | {| class="wikitable" style="float:right; margin-left: 5px;"
| |
| − | |-
| |
| − | |[[#top|back to top]]
| |
| − | |}
| |
| − | ===Regimen {{#subobject:5bf868|Variant=1}}===
| |
| − | {| class="wikitable" style="width: 100%; text-align:center;"
| |
| − | !Study
| |
| − | ![[Levels_of_Evidence#Evidence|Evidence]]
| |
| − | |-
| |
| − | |[https://onlinelibrary.wiley.com/doi/10.1002/%28SICI%291097-0142%2820000501%2988:9%3C2037::AID-CNCR8%3E3.0.CO;2-K/full Sternberg et al. 2000]
| |
| | | style="background-color:#91cf61" |Phase II | | | style="background-color:#91cf61" |Phase II |
| | |- | | |- |
| | |} | | |} |
| | + | ''Patients were required to have a FLT3 ITD or FLT3 p.D835Y mutation.'' |
| | ====Chemotherapy==== | | ====Chemotherapy==== |
| − | *[[Cytarabine (Cytosar)]] 500 mg/m<sup>2</sup> IV over 90 minutes every 12 hours on days 1 to 6 (12 total doses) | + | *[[Midostaurin (Rydapt)]] 75 mg PO TID |
| − | *[[Mitoxantrone (Novantrone)]] 5 mg/m<sup>2</sup> IV bolus once per day on days 1 to 5
| |
| | | | |
| − | ===References===
| + | '''28-day cycles''' |
| − | # 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. [https://onlinelibrary.wiley.com/doi/10.1002/%28SICI%291097-0142%2820000501%2988:9%3C2037::AID-CNCR8%3E3.0.CO;2-K/full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/10813714 PubMed]
| |
| − | | |
| − | ==Etoposide & Mitoxantrone {{#subobject:3f0d63|Regimen=1}}==
| |
| − | {| class="wikitable" style="float:right; margin-left: 5px;"
| |
| − | |-
| |
| − | |[[#top|back to top]]
| |
| − | |}
| |
| − | ===Regimen {{#subobject:7683cc|Variant=1}}===
| |
| − | {| class="wikitable" style="width: 100%; text-align:center;"
| |
| − | !Study
| |
| − | ![[Levels_of_Evidence#Evidence|Evidence]]
| |
| − | |'''ORR'''
| |
| − | |-
| |
| − | |[http://jco.ascopubs.org/content/6/2/213.abstract Ho et al. 1988]
| |
| − | | style="background-color:#91cf61" |Phase II
| |
| − | |54%
| |
| − | |-
| |
| − | |}
| |
| − | ====Chemotherapy====
| |
| − | *[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1 to 5
| |
| − | *[[Mitoxantrone (Novantrone)]] 10 mg/m<sup>2</sup> IV over 15 minutes once per day on days 1 to 5
| |
| | | | |
| | ===References=== | | ===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. [http://jco.ascopubs.org/content/6/2/213.abstract link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/3422260 PubMed] | + | # Stone RM, DeAngelo DJ, Klimek V, Galinsky I, Estey E, Nimer SD, Grandin W, Lebwohl D, Wang Y, Cohen P, Fox EA, Neuberg D, Clark J, Gilliland DG, Griffin JD. Patients with acute myeloid leukemia and an activating mutation in FLT3 respond to a small-molecule FLT3 tyrosine kinase inhibitor, PKC412. Blood. 2005 Jan 1;105(1):54-60. Epub 2004 Sep 2. [http://www.bloodjournal.org/content/105/1/54.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/15345597 PubMed] |
| | + | <!-- Presented in part at the 45th Annual Meeting of the American Society of Hematology, December 6-9, 2003, San Diego, CA. --> |
| | + | # Fischer T, Stone RM, Deangelo DJ, Galinsky I, Estey E, Lanza C, Fox E, Ehninger G, Feldman EJ, Schiller GJ, Klimek VM, Nimer SD, Gilliland DG, Dutreix C, Huntsman-Labed A, Virkus J, Giles FJ. Phase IIB trial of oral Midostaurin (PKC412), the FMS-like tyrosine kinase 3 receptor (FLT3) and multi-targeted kinase inhibitor, in patients with acute myeloid leukemia and high-risk myelodysplastic syndrome with either wild-type or mutated FLT3. J Clin Oncol. 2010 Oct 1;28(28):4339-45. Epub 2010 Aug 23. [http://jco.ascopubs.org/content/28/28/4339.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4135183/ link to PMC article] '''contains verified protocol'''[https://www.ncbi.nlm.nih.gov/pubmed/20733134 PubMed] |
| | | | |
| − | ==FLAG {{#subobject:551761|Regimen=1}}== | + | =Relapsed or refractory, further lines of therapy= |
| | + | ==Azacitidine & Sorafenib {{#subobject:e3a8ee|Regimen=1}}== |
| | {| class="wikitable" style="float:right; margin-left: 5px;" | | {| class="wikitable" style="float:right; margin-left: 5px;" |
| | |- | | |- |
| | |[[#top|back to top]] | | |[[#top|back to top]] |
| | |} | | |} |
| − | FLAG: '''<u>FL</u>'''udarabine, '''<u>A</u>'''ra-C (Cytarabine), '''<u>G</u>'''-CSF
| |
| − | ===Variant #1, weight-based G-CSF {{#subobject:9501d2|Variant=1}}===
| |
| − | {| class="wikitable" style="width: 100%; text-align:center;"
| |
| − | !Study
| |
| − | ![[Levels_of_Evidence#Evidence|Evidence]]
| |
| − | |-
| |
| − | |[https://onlinelibrary.wiley.com/doi/10.1002/%28SICI%291096-8652%28199806%2958:2%3C105::AID-AJH3%3E3.0.CO;2-W/abstract Montillo et al. 1998]
| |
| − | | style="background-color:#91cf61" |Phase II
| |
| − | |-
| |
| − | |}
| |
| − | ====Chemotherapy====
| |
| − | *[[Fludarabine (Fludara)]] 30 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1 to 5, '''given first'''
| |
| − | *[[Cytarabine (Cytosar)]] 2000 mg/m<sup>2</sup> IV over 4 hours once per day on days 1 to 5, '''given last, 4 hours after the start of [[Fludarabine (Fludara)]]'''
| |
| − | *[[Filgrastim (Neupogen)]] or [[Lenograstim (Granocyte)]] 5 mcg/kg SC once per day 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
| |
| | | | |
| − | '''One course'''
| + | ===Regimen {{#subobject:9c1ff|Variant=1}}=== |
| − | ===Variant #2, BSA-based G-CSF {{#subobject:bdc7e4|Variant=1}}===
| |
| − | {| class="wikitable" style="width: 100%; text-align:center;"
| |
| − | !Study
| |
| − | ![[Levels_of_Evidence#Evidence|Evidence]]
| |
| − | !Comparator
| |
| − | ![[Levels_of_Evidence#Efficacy|Efficacy]]
| |
| − | |-
| |
| − | |[http://ascopubs.org/doi/full/10.1200/JCO.2012.43.7384 Kaspers et al. 2013 (I-BFM-SG 2001/01)]
| |
| − | | style="background-color:#1a9851" |Phase III (C)
| |
| − | |[[#FLAG-DNX|FLAG-DNX]]
| |
| − | | style="background-color:#fc8d59" |Seems to have inferior CR rate
| |
| − | |-
| |
| − | |}
| |
| − | ''Note: this regimen was studied in patients up to 21 years of age.''
| |
| − | ====Chemotherapy====
| |
| − | *[[Fludarabine (Fludara)]] 30 mg/m<sup>2</sup> IV once per day on days 1 to 5, '''given second'''
| |
| − | *[[Cytarabine (Cytosar)]] 2000 mg/m<sup>2</sup> IV once per day on days 1 to 5, '''given last, 4 hours after the start of [[Fludarabine (Fludara)]]'''
| |
| − | *[[Filgrastim (Neupogen)]] 200 mcg/m<sup>2</sup> (route not specified) once per day on days 0 to 5, '''given first'''
| |
| − | | |
| − | '''Two cycles'''
| |
| − | ====Subsequent treatment====
| |
| − | *[[#CYVE_2|CYVE]] or [[#Cytarabine_.26_Thioguanine|Cytarabine & Thioguanine]] consolidation, as a bridge to [[#Allogeneic_hematopoietic_stem_cell_transplant_2|allogeneic HSCT]]
| |
| − | ===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. [https://onlinelibrary.wiley.com/doi/10.1002/%28SICI%291096-8652%28199806%2958:2%3C105::AID-AJH3%3E3.0.CO;2-W/abstract link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/9625576 PubMed]
| |
| − | # Kaspers GJ, Zimmermann M, Reinhardt D, Gibson BE, Tamminga RY, Aleinikova O, Armendariz H, Dworzak M, Ha SY, Hasle H, Hovi L, Maschan A, Bertrand Y, Leverger GG, Razzouk BI, Rizzari C, Smisek P, Smith O, Stark B, Creutzig U. Improved outcome in pediatric relapsed acute myeloid leukemia: results of a randomized trial on liposomal daunorubicin by the International BFM Study Group. J Clin Oncol. 2013 Feb 10;31(5):599-607. Epub 2013 Jan 14. [http://ascopubs.org/doi/full/10.1200/JCO.2012.43.7384 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/23319696 PubMed]
| |
| − | | |
| − | ==FLAG-DNX {{#subobject:665bd2|Regimen=1}}==
| |
| − | {| class="wikitable" style="float:right; margin-left: 5px;"
| |
| − | |-
| |
| − | |[[#top|back to top]]
| |
| − | |}
| |
| − | FLAG-DNX: '''<u>FL</u>'''udarabine, '''<u>A</u>'''ra-C (Cytarabine), '''<u>G</u>'''-CSF, '''<u>D</u>'''au'''<u>N</u>'''o'''<u>X</u>'''ome (Daunorubicin liposomal)
| |
| − | ===Regimen {{#subobject:6494d7|Variant=1}}===
| |
| − | {| class="wikitable" style="width: 100%; text-align:center;"
| |
| − | !Study
| |
| − | ![[Levels_of_Evidence#Evidence|Evidence]]
| |
| − | !Comparator
| |
| − | ![[Levels_of_Evidence#Efficacy|Efficacy]]
| |
| − | |-
| |
| − | |[http://ascopubs.org/doi/full/10.1200/JCO.2012.43.7384 Kaspers et al. 2013 (I-BFM-SG 2001/01)]
| |
| − | | style="background-color:#1a9851" |Phase III (E)
| |
| − | |[[#FLAG|FLAG]]
| |
| − | | style="background-color:#91cf60" |Seems to have superior CR rate
| |
| − | |-
| |
| − | |}
| |
| − | ''Note: this regimen was studied in patients up to 21 years of age.''
| |
| − | ====Chemotherapy====
| |
| − | *[[Fludarabine (Fludara)]] 30 mg/m<sup>2</sup> IV once per day on days 1 to 5, '''given second'''
| |
| − | *[[Cytarabine (Cytosar)]] 2000 mg/m<sup>2</sup> IV once per day on days 1 to 5, '''given last, 4 hours after the start of [[Fludarabine (Fludara)]]'''
| |
| − | *[[Filgrastim (Neupogen)]] 200 mcg/m<sup>2</sup> (route not specified) once per day on days 0 to 5, '''given first'''
| |
| − | *[[Daunorubicin liposomal (DaunoXome)]] as follows:
| |
| − | **Cycle 1: 60 mg/m<sup>2</sup> IV once per day on days 1, 3, 5, '''given third'''
| |
| − | **Cycle 2: none
| |
| − | | |
| − | '''2 cycles'''
| |
| − | ====Subsequent treatment====
| |
| − | *[[#CYVE_2|CYVE]] or [[#Cytarabine_.26_Thioguanine|Cytarabine & Thioguanine]] consolidation, as a bridge to [[#Allogeneic_hematopoietic_stem_cell_transplant_2|allogeneic HSCT]]
| |
| − | ===References===
| |
| − | # Kaspers GJ, Zimmermann M, Reinhardt D, Gibson BE, Tamminga RY, Aleinikova O, Armendariz H, Dworzak M, Ha SY, Hasle H, Hovi L, Maschan A, Bertrand Y, Leverger GG, Razzouk BI, Rizzari C, Smisek P, Smith O, Stark B, Creutzig U. Improved outcome in pediatric relapsed acute myeloid leukemia: results of a randomized trial on liposomal daunorubicin by the International BFM Study Group. J Clin Oncol. 2013 Feb 10;31(5):599-607. Epub 2013 Jan 14. [http://ascopubs.org/doi/full/10.1200/JCO.2012.43.7384 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/23319696 PubMed]
| |
| − | | |
| − | ==FLAG-Ida {{#subobject:d8c75b|Regimen=1}}==
| |
| − | {| class="wikitable" style="float:right; margin-left: 5px;"
| |
| − | |-
| |
| − | |[[#top|back to top]]
| |
| − | |}
| |
| − | FLAG-Ida: '''<u>FL</u>'''udarabine, '''<u>A</u>'''ra-C (Cytarabine), '''<u>G</u>'''-CSF (Filgrastim), '''<u>Ida</u>'''rubicin
| |
| − | ===Regimen {{#subobject:5fa1bb|Variant=1}}=== | |
| | {| class="wikitable" style="width: 100%; text-align:center;" | | {| class="wikitable" style="width: 100%; text-align:center;" |
| | !Study | | !Study |
| | ![[Levels_of_Evidence#Evidence|Evidence]] | | ![[Levels_of_Evidence#Evidence|Evidence]] |
| | |- | | |- |
| − | |[https://www.ncbi.nlm.nih.gov/pubmed/9432047 Parker et al. 1997] | + | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3674666/ Ravandi et al. 2013] |
| − | | style="background-color:#ffffbe" |Phase II, <20 patients
| |
| − | |-
| |
| − | |[https://link.springer.com/article/10.1007%2Fs00277-003-0624-2 Pastore et al. 2003]
| |
| | | style="background-color:#91cf61" |Phase II | | | style="background-color:#91cf61" |Phase II |
| | |- | | |- |
| | |} | | |} |
| | ====Chemotherapy==== | | ====Chemotherapy==== |
| − | *[[Fludarabine (Fludara)]] 30 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1 to 5, given first | + | *[[Azacitidine (Vidaza)]] 75 mg/m<sup>2</sup> SC or IV once per day on days 1 to 7 |
| − | *[[Cytarabine (Cytosar)]] 2000 mg/m<sup>2</sup> IV over 4 hours once per day on days 1 to 5, given second, 4 hours after [[Fludarabine (Fludara)]]
| + | *[[Sorafenib (Nexavar)]] 400 mg PO BID |
| − | *[[Filgrastim (Neupogen)]] 5 mcg/kg SC once per day starting on day 6, to continue until neutrophil recovery
| |
| − | *[[Idarubicin (Idamycin)]] 10 mg/m<sup>2</sup> IV once per day on days 1 to 3
| |
| − | | |
| − | ===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. [https://www.ncbi.nlm.nih.gov/pubmed/9432047 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. [https://link.springer.com/article/10.1007%2Fs00277-003-0624-2 link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/12707726 PubMed]
| |
| − | | |
| − | ==F-SHAI {{#subobject:9e1c5f|Regimen=1}}==
| |
| − | {| class="wikitable" style="float:right; margin-left: 5px;"
| |
| − | |-
| |
| − | |[[#top|back to top]]
| |
| − | |}
| |
| − | F-SHAI: '''<u>F</u>'''ludarabine, '''<u>S</u>'''equential '''<u>H</u>'''igh-dose '''<u>A</u>'''ra-C (cytarabine), '''<u>I</u>'''darubicin
| |
| − | | |
| − | ===Regimen {{#subobject:b50224|Variant=1}}===
| |
| − | {| class="wikitable" style="width: 100%; text-align:center;"
| |
| − | !Study
| |
| − | ![[Levels_of_Evidence#Evidence|Evidence]]
| |
| − | !Comparator
| |
| − | ![[Levels_of_Evidence#Efficacy|Efficacy]]
| |
| − | |-
| |
| − | |[https://www.nature.com/leu/journal/v28/n5/full/leu2013297a.html Fiegl et al. 2013]
| |
| − | | style="background-color:#1a9851" |Phase III (E)
| |
| − | |[[#SHAI|SHAI]]
| |
| − | | style="background-color:#91cf60" |Seems to have superior TTTF
| |
| − | |-
| |
| − | |}
| |
| − | ====Chemotherapy====
| |
| − | *[[Fludarabine (Fludara)]] 15 mg/m<sup>2</sup> IV BID on days 1, 2, 8, 9, '''4 hours prior to each cytarabine dose'''
| |
| − | *[[Cytarabine (Cytosar)]] 1000 mg/m<sup>2</sup> IV BID on days 1, 2, 8, 9 | |
| − | **Dose increased to 3000 mg/m<sup>2</sup> for patients 60 or younger with refractory AML or greater than or equal to 2nd relapse
| |
| − | *[[Idarubicin (Idamycin)]] 10 mg/m<sup>2</sup> IV once per day on days 3, 4, 10, 11
| |
| | | | |
| | ====Supportive medications==== | | ====Supportive medications==== |
| − | *[[:Category:Granulocyte_colony-stimulating_factors|G-CSF]] 5 mcg/kg SC once per day from day 14 until ANC greater than 1500/uL | + | * "All patients received antimicrobials, supportive care, and transfusions of blood products according to the institutional guidelines." |
| − | **Discontinued if the post-treatment bmbx had greater than 5% bone marrow blasts
| |
| − | | |
| − | '''One course'''
| |
| − | | |
| − | ===References===
| |
| − | # Fiegl M, Unterhalt M, Kern W, Braess J, Spiekermann K, Staib P, Grüneisen A, Wörmann B, Schöndube D, Serve H, Reichle A, Hentrich M, Schiel X, Sauerland C, Heinecke A, Rieger C, Beelen D, Berdel WE, Büchner T, Hiddemann W. Chemomodulation of sequential high-dose cytarabine by fludarabine in relapsed or refractory acute myeloid leukemia: a randomized trial of the AMLCG. Leukemia. 2014 May;28(5):1001-7. Epub 2013 Oct 22. [https://www.nature.com/leu/journal/v28/n5/full/leu2013297a.html link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/24150216 PubMed]
| |
| − | | |
| − | ==IAP {{#subobject:7a1294|Regimen=1}}==
| |
| − | {| class="wikitable" style="float:right; margin-left: 5px;"
| |
| − | |-
| |
| − | |[[#top|back to top]]
| |
| − | |}
| |
| − | IAP: '''<u>I</u>'''darubicin, '''<u>A</u>'''ra-C (cytarabine), '''<u>P</u>'''ravastatin
| |
| − | | |
| − | ===Regimen {{#subobject:a442bc|Variant=1}}===
| |
| − | {| class="wikitable" style="width: 100%; text-align:center;"
| |
| − | !Study
| |
| − | ![[Levels_of_Evidence#Evidence|Evidence]]
| |
| − | |-
| |
| − | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4188732/ Advani et al. 2014 (SWOG S0919)]
| |
| − | | style="background-color:#91cf61" |Phase II
| |
| − | |-
| |
| − | |}
| |
| − | ====Chemotherapy====
| |
| − | *[[Idarubicin (Idamycin)]] 12 mg/m<sup>2</sup> IV once per day on days 4 to 6
| |
| − | *[[Cytarabine (Cytosar)]] 1500 mg/m<sup>2</sup> IV once per day on days 4 to 7
| |
| − | *[[Pravastatin (Pravachol)]] 1280 mg PO once per day on days 1 to 8
| |
| − | | |
| − | '''Patients achieving a CR could receive 2 cycles of consolidation'''
| |
| − | | |
| − | ===References===
| |
| − | <!-- # '''Abstract:''' 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). [http://meetinglibrary.asco.org/content/111137-132 link to abstract] '''contains verified protocol''' -->
| |
| − | # Advani AS, McDonough S, Copelan E, Willman C, Mulford DA, List AF, Sekeres MA, Othus M, Appelbaum FR. SWOG0919: a Phase 2 study of idarubicin and cytarabine in combination with pravastatin for relapsed acute myeloid leukaemia. Br J Haematol. 2014 Oct;167(2):233-7. Epub 2014 Jul 18. [https://onlinelibrary.wiley.com/doi/10.1111/bjh.13035/full link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4188732/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/25039477 PubMed]
| |
| − | | |
| − | ==MEC {{#subobject:48e49b|Regimen=1}}==
| |
| − | {| class="wikitable" style="float:right; margin-left: 5px;"
| |
| − | |-
| |
| − | |[[#top|back to top]]
| |
| − | |}
| |
| − | MEC: '''<u>M</u>'''itoxantrone, '''<u>E</u>'''toposide, '''<u>C</u>'''ytarabine
| |
| − | | |
| − | ===Variant #1 {{#subobject:9ad362|Variant=1}}===
| |
| − | {| class="wikitable" style="width: 100%; text-align:center;"
| |
| − | !Study
| |
| − | ![[Levels_of_Evidence#Evidence|Evidence]]
| |
| − | !Comparator
| |
| − | ![[Levels_of_Evidence#Efficacy|Efficacy]]
| |
| − | |-
| |
| − | |[http://jco.ascopubs.org/content/23/18/4110.long Feldman et al. 2005]
| |
| − | | style="background-color:#1a9851" |Phase III (C)
| |
| − | |MEC & Lintuzumab
| |
| − | | style="background-color:#ffffbf" |Seems not superior
| |
| − | |-
| |
| − | |}
| |
| − | ====Chemotherapy====
| |
| − | *[[Mitoxantrone (Novantrone)]] 8 mg/m<sup>2</sup> IV once per day on days 1 to 6
| |
| − | *[[Etoposide (Vepesid)]] 80 mg/m<sup>2</sup> IV once per day on days 1 to 6
| |
| − | *[[Cytarabine (Cytosar)]] 1000 mg/m<sup>2</sup> IV once per day on days 1 to 6
| |
| − | | |
| − | ===Variant #2 {{#subobject:ac3985|Variant=1}}===
| |
| − | {| class="wikitable" style="width: 100%; text-align:center;"
| |
| − | !Study
| |
| − | ![[Levels_of_Evidence#Evidence|Evidence]]
| |
| − | |-
| |
| − | |[http://jco.ascopubs.org/content/9/7/1210.long Amadori et al. 1991]
| |
| − | | style="background-color:#91cf61" |Phase II
| |
| − | |-
| |
| − | |}
| |
| − | ====Chemotherapy====
| |
| − | *[[Mitoxantrone (Novantrone)]] 6 mg/m<sup>2</sup> IV bolus once per day on days 1 to 6
| |
| − | *[[Etoposide (Vepesid)]] 80 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1 to 6
| |
| − | *[[Cytarabine (Cytosar)]] 1000 mg/m<sup>2</sup> IV over 6 hours once per day on days 1 to 6
| |
| − | | |
| − | ===Variant #3 {{#subobject:bd7f87|Variant=1}}===
| |
| − | {| class="wikitable" style="width: 100%; text-align:center;"
| |
| − | !Study
| |
| − | ![[Levels_of_Evidence#Evidence|Evidence]]
| |
| − | |-
| |
| − | |[https://onlinelibrary.wiley.com/doi/10.1002/ajh.21857/full Kohrt et al. 2010]
| |
| − | | style="background-color:#ffffbe" |Retrospective
| |
| − | |-
| |
| − | |}
| |
| − | ====Chemotherapy====
| |
| − | *[[Mitoxantrone (Novantrone)]] 8 mg/m<sup>2</sup> IV push once per day on days 1 to 5, '''given third'''
| |
| − | *[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV over 2 hours once per day on days 1 to 5, '''given first'''
| |
| − | *[[Cytarabine (Cytosar)]] 1000 mg/m<sup>2</sup> IV once per day 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. [http://jco.ascopubs.org/content/9/7/1210.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/2045861 PubMed]
| |
| − | # '''Retrospective:''' 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. [https://onlinelibrary.wiley.com/doi/10.1002/ajh.21857/full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/20872554 PubMed]
| |
| − | # Feldman EJ, Brandwein J, Stone R, Kalaycio M, Moore J, O'Connor J, Wedel N, Roboz GJ, Miller C, Chopra R, Jurcic JC, Brown R, Ehmann WC, Schulman P, Frankel SR, De Angelo D, Scheinberg D. Phase III randomized multicenter study of a humanized anti-CD33 monoclonal antibody, lintuzumab, in combination with chemotherapy, versus chemotherapy alone in patients with refractory or first-relapsed acute myeloid leukemia. J Clin Oncol. 2005 Jun 20;23(18):4110-6. [http://jco.ascopubs.org/content/23/18/4110.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/15961759 PubMed]
| |
| − | | |
| − | ==SHAI {{#subobject:6f1931|Regimen=1}}==
| |
| − | {| class="wikitable" style="float:right; margin-left: 5px;"
| |
| − | |-
| |
| − | |[[#top|back to top]]
| |
| − | |}
| |
| − | SHAI: '''<u>S</u>'''equential '''<u>H</u>'''igh-dose '''<u>A</u>'''ra-C (Cytarabine), '''<u>I</u>'''darubicin
| |
| − | | |
| − | ===Regimen {{#subobject:2b40b3|Variant=1}}===
| |
| − | {| class="wikitable" style="width: 100%; text-align:center;"
| |
| − | !Study
| |
| − | ![[Levels_of_Evidence#Evidence|Evidence]]
| |
| − | !Comparator
| |
| − | ![[Levels_of_Evidence#Efficacy|Efficacy]]
| |
| − | |-
| |
| − | |[https://www.nature.com/leu/journal/v28/n5/full/leu2013297a.html Fiegl et al. 2013]
| |
| − | | style="background-color:#1a9851" |Phase III (C)
| |
| − | |[[#F-SHAI|F-SHAI]]
| |
| − | | style="background-color:#fc8d59" |Seems to have inferior TTTF
| |
| − | |-
| |
| − | |}
| |
| − | ====Chemotherapy====
| |
| − | *[[Cytarabine (Cytosar)]] 1000 mg/m<sup>2</sup> IV BID on days 1, 2, 8, 9
| |
| − | **Dose increased to 3000 mg/m<sup>2</sup> for patients 60 or younger with refractory AML or greater than or equal to 2nd relapse
| |
| − | *[[Idarubicin (Idamycin)]] 10 mg/m<sup>2</sup> IV once per day on days 3, 4, 10, 11
| |
| | | | |
| − | '''One course''' | + | '''4 to 8 week cycles at treating physician's discretion''' |
| − | | |
| − | ===References===
| |
| − | # Fiegl M, Unterhalt M, Kern W, Braess J, Spiekermann K, Staib P, Grüneisen A, Wörmann B, Schöndube D, Serve H, Reichle A, Hentrich M, Schiel X, Sauerland C, Heinecke A, Rieger C, Beelen D, Berdel WE, Büchner T, Hiddemann W. Chemomodulation of sequential high-dose cytarabine by fludarabine in relapsed or refractory acute myeloid leukemia: a randomized trial of the AMLCG. Leukemia. 2014 May;28(5):1001-7. Epub 2013 Oct 22. [https://www.nature.com/leu/journal/v28/n5/full/leu2013297a.html link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/24150216 PubMed]
| |
| − | | |
| − | =Consolidation after salvage therapy=
| |
| − | ==Allogeneic hematopoietic stem cell transplant==
| |
| − | {| class="wikitable" style="float:right; margin-left: 5px;"
| |
| − | |-
| |
| − | |[[#top|back to top]]
| |
| − | |}
| |
| − | To be completed.
| |
| − | | |
| − | ==Cytarabine & Thioguanine {{#subobject:3c38bc|Regimen=1}}==
| |
| − | {| class="wikitable" style="float:right; margin-left: 5px;"
| |
| − | |-
| |
| − | |[[#top|back to top]]
| |
| − | |}
| |
| − | ===Regimen {{#subobject:f2728e|Variant=1}}===
| |
| − | {| class="wikitable" style="width: 100%; text-align:center;"
| |
| − | !Study
| |
| − | ![[Levels_of_Evidence#Evidence|Evidence]]
| |
| − | |-
| |
| − | |[http://ascopubs.org/doi/full/10.1200/JCO.2012.43.7384 Kaspers et al. 2013 (I-BFM-SG 2001/01)]
| |
| − | | style="background-color:#91cf61" |Non-randomized portion of RCT
| |
| − | |-
| |
| − | |}
| |
| − | ''Note: this regimen was studied in patients up to 21 years of age, and was intended for use when the time to transplant would be relatively short or for patients in "poor condition".''
| |
| − | ====Preceding treatment====
| |
| − | *[[#FLAG|FLAG]] versus [[#FLAG-DNX|FLAG-DNX]]
| |
| − | ====Chemotherapy====
| |
| − | *[[Cytarabine (Cytosar)]] 75 mg/m<sup>2</sup> SC once per day on days 1 to 4, every other week
| |
| − | *[[Thioguanine (Tabloid)]] 100 mg/m<sup>2</sup> PO once per day for up to 4 weeks maximum
| |
| − | ====Subsequent treatment====
| |
| − | *[[#Allogeneic_hematopoietic_stem_cell_transplant_2|allogeneic HSCT]]
| |
| − | ===References===
| |
| − | # Kaspers GJ, Zimmermann M, Reinhardt D, Gibson BE, Tamminga RY, Aleinikova O, Armendariz H, Dworzak M, Ha SY, Hasle H, Hovi L, Maschan A, Bertrand Y, Leverger GG, Razzouk BI, Rizzari C, Smisek P, Smith O, Stark B, Creutzig U. Improved outcome in pediatric relapsed acute myeloid leukemia: results of a randomized trial on liposomal daunorubicin by the International BFM Study Group. J Clin Oncol. 2013 Feb 10;31(5):599-607. Epub 2013 Jan 14. [http://ascopubs.org/doi/full/10.1200/JCO.2012.43.7384 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/23319696 PubMed]
| |
| − | | |
| − | ==CYVE {{#subobject:4bd791|Regimen=1}}==
| |
| − | {| class="wikitable" style="float:right; margin-left: 5px;"
| |
| − | |-
| |
| − | |[[#top|back to top]]
| |
| − | |}
| |
| − | CYVE: '''<u>CY</u>'''tarabine & '''<u>VE</u>'''pesid (Etoposide)
| |
| − | ===Regimen {{#subobject:a16529|Variant=1}}===
| |
| − | {| class="wikitable" style="width: 100%; text-align:center;"
| |
| − | !Study
| |
| − | ![[Levels_of_Evidence#Evidence|Evidence]]
| |
| − | |-
| |
| − | |[http://ascopubs.org/doi/full/10.1200/JCO.2012.43.7384 Kaspers et al. 2013 (I-BFM-SG 2001/01)]
| |
| − | | style="background-color:#91cf61" |Non-randomized portion of RCT
| |
| − | |-
| |
| − | |}
| |
| − | ''Note: this regimen was studied in patients up to 21 years of age. It is unclear if the course is repeated more than once.''
| |
| − | ====Preceding treatment====
| |
| − | *[[#FLAG|FLAG]] versus [[#FLAG-DNX|FLAG-DNX]]
| |
| − | ====Chemotherapy====
| |
| − | *[[Cytarabine (Cytosar)]] 500 mg/m<sup>2</sup>/day IV continuous infusion on days 1 to 4 (total dose: 2000 mg/m<sup>2</sup>)
| |
| − | *[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV BID on days 1 to 4
| |
| − | ====Subsequent treatment====
| |
| − | *[[#Allogeneic_hematopoietic_stem_cell_transplant_2|allogeneic HSCT]]
| |
| − | ===References===
| |
| − | # Kaspers GJ, Zimmermann M, Reinhardt D, Gibson BE, Tamminga RY, Aleinikova O, Armendariz H, Dworzak M, Ha SY, Hasle H, Hovi L, Maschan A, Bertrand Y, Leverger GG, Razzouk BI, Rizzari C, Smisek P, Smith O, Stark B, Creutzig U. Improved outcome in pediatric relapsed acute myeloid leukemia: results of a randomized trial on liposomal daunorubicin by the International BFM Study Group. J Clin Oncol. 2013 Feb 10;31(5):599-607. Epub 2013 Jan 14. [http://ascopubs.org/doi/full/10.1200/JCO.2012.43.7384 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/23319696 PubMed]
| |
| − | | |
| − | =Relapsed or refractory, subsequent lines of therapy=
| |
| − | ''Note: these regimens are generally intended to delay progression of disease and are of non-curative intent.''
| |
| − | | |
| − | ==Azacitidine monotherapy {{#subobject:531b70|Regimen=1}}==
| |
| − | {| class="wikitable" style="float:right; margin-left: 5px;"
| |
| − | |-
| |
| − | |[[#top|back to top]]
| |
| − | |}
| |
| − | ===Regimen {{#subobject:39f96a|Variant=1}}===
| |
| − | {| class="wikitable" style="width: 100%; text-align:center;"
| |
| − | !Study
| |
| − | ![[Levels_of_Evidence#Evidence|Evidence]]
| |
| − | |-
| |
| − | |[http://www.bloodjournal.org/content/116/19/3735.long Thepot et al. 2010]
| |
| − | | style="background-color:#91cf61" |Phase II
| |
| − | |-
| |
| − | |}
| |
| − | ====Chemotherapy====
| |
| − | *[[Azacitidine (Vidaza)]] 75 mg/m<sup>2</sup> SC once per day on days 1 to 7
| |
| − | | |
| − | '''28-day cycle for at least 4 to 6 cycles'''
| |
| | | | |
| | ===References=== | | ===References=== |
| | <!-- no pre-pub disclosed --> | | <!-- no pre-pub disclosed --> |
| − | # 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. [http://www.bloodjournal.org/content/116/19/3735.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/20664061 PubMed] | + | # 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. Epub 2013 Apr 23. [http://www.bloodjournal.org/content/121/23/4655.full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3674666/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/23613521 PubMed] |
| − | | |
| − | ==Azacitidine, Vorinostat, Gemtuzumab ozogamicin {{#subobject:go18ee|Regimen=1}}==
| |
| − | {| class="wikitable" style="float:right; margin-left: 5px;"
| |
| − | |-
| |
| − | |[[#top|back to top]]
| |
| − | |}
| |
| − | ===Regimen {{#subobject:9cgo2f|Variant=1}}===
| |
| − | {| class="wikitable" style="width: 100%; text-align:center;"
| |
| − | !Study
| |
| − | ![[Levels_of_Evidence#Evidence|Evidence]]
| |
| − | |-
| |
| − | |[http://www.haematologica.org/content/99/1/54.full Walter et al. 2013]
| |
| − | | style="background-color:#91cf61" |Phase I/II
| |
| − | |-
| |
| − | |}
| |
| − | ''This is the MTD used in the phase II portion, which was tested on 43 patients.''
| |
| − | ====Chemotherapy====
| |
| − | *[[Azacitidine (Vidaza)]] 75 mg/m<sup>2</sup> SC or IV once per day on days 1 to 7
| |
| − | *[[Vorinostat (Zolinza)]] 400 mg PO once per day on days 1 to 9
| |
| − | *[[Gemtuzumab ozogamicin (Mylotarg)]] 3 mg/m<sup>2</sup> IV once on days 4 & 8
| |
| − | | |
| − | '''Up to 6 cycles based on response; cycle length not specified beyond 2nd cycle'''
| |
| − | | |
| − | ===References===
| |
| − | # Walter RB, Medeiros BC, Gardner KM, Orlowski KF, Gallegos L, Scott BL, Hendrie PC, Estey EH. Gemtuzumab ozogamicin in combination with vorinostat and azacitidine in older patients with relapsed or refractory acute myeloid leukemia: a phase 1/2 study. Haematologica. 2014 Jan;99(1):54-9. Epub 2013 Oct 18. [http://www.haematologica.org/content/99/1/54.full link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24142996/ link to PMC article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/24142996 PubMed]
| |
| − | | |
| − | ==Ruxolitinib monotherapy {{#subobject:ad5c7c|Regimen=1}}==
| |
| − | {| class="wikitable" style="float:right; margin-left: 5px;"
| |
| − | |-
| |
| − | |[[#top|back to top]]
| |
| − | |}
| |
| − | | |
| − | ===Regimen {{#subobject:596d8b|Variant=1}}===
| |
| − | {| class="wikitable" style="width: 100%; text-align:center;"
| |
| − | !Study
| |
| − | ![[Levels_of_Evidence#Evidence|Evidence]]
| |
| − | |-
| |
| − | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4081383/ Eghtedar et al. 2012]
| |
| − | | style="background-color:#91cf61" |Phase II
| |
| − | |-
| |
| − | |}
| |
| − | ====Chemotherapy====
| |
| − | *[[Ruxolitinib (Jakafi)]] 25 mg PO BID
| |
| − | | |
| − | '''28-day cycles'''
| |
| − | | |
| − | ''Patients with progression were allowed to increase the dose to 50 mg PO BID''
| |
| − | | |
| − | ===References===
| |
| − | <!-- This study was presented in part at the American Society of Hematology annual meeting, December 2010, Orlando, FL. -->
| |
| − | # Eghtedar A, Verstovsek S, Estrov Z, Burger J, Cortes J, Bivins C, Faderl S, Ferrajoli A, Borthakur G, George S, Scherle PA, Newton RC, Kantarjian HM, Ravandi F. Phase 2 study of the JAK kinase inhibitor ruxolitinib in patients with refractory leukemias, including postmyeloproliferative neoplasm acute myeloid leukemia. Blood. 2012 May 17;119(20):4614-8. Epub 2012 Mar 15. [http://www.bloodjournal.org/content/119/20/4614.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4081383/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/22422826 PubMed]
| |
| − | | |
| − | =Response criteria=
| |
| − | ==NCI-sponsored workshop on definitions of diagnosis and response in acute myeloid leukemia (1990)==
| |
| − | # Cheson BD, Cassileth PA, Head DR, Schiffer CA, Bennett JM, Bloomfield CD, Brunning R, Gale RP, Grever MR, Keating MJ, et al. Report of the National Cancer Institute-sponsored workshop on definitions of diagnosis and response in acute myeloid leukemia. J Clin Oncol. 1990 May;8(5):813-9. Review. [http://jco.ascopubs.org/content/8/5/813.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/2185339 PubMed]
| |
| − | | |
| − | ==Revised International Working Group recommendations (2003)==
| |
| − | # Cheson BD, Bennett JM, Kopecky KJ, Büchner T, Willman CL, Estey EH, Schiffer CA, Doehner H, Tallman MS, Lister TA, Lo-Coco F, Willemze R, Biondi A, Hiddemann W, Larson RA, Löwenberg B, Sanz MA, Head DR, Ohno R, Bloomfield CD; International Working Group for Diagnosis, Standardization of Response Criteria, Treatment Outcomes, and Reporting Standards for Therapeutic Trials in Acute Myeloid Leukemia. Revised recommendations of the International Working Group for Diagnosis, Standardization of Response Criteria, Treatment Outcomes, and Reporting Standards for Therapeutic Trials in Acute Myeloid Leukemia. J Clin Oncol. 2003 Dec 15;21(24):4642-9. Erratum in: J Clin Oncol. 2004 Feb 1;22(3):576. LoCocco, Francesco [corrected to Lo-Coco, Francesco]. [http://jco.ascopubs.org/content/21/24/4642.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/14673054 PubMed]
| |
| − | | |
| − | =Prognosis=
| |
| − | | |
| − | ==Prognostic Index for Adult Patients With Acute Myeloid Leukemia in First Relapse (2005)==
| |
| − | {| class="wikitable" style="float:right; margin-left: 5px;"
| |
| − | |-
| |
| − | |[[#top|back to top]]
| |
| − | |}
| |
| − | | |
| − | *Relapse-free interval from first complete remission
| |
| − | **Greater than 18 months (0 points)
| |
| − | **7 to 18 months ('''3 points''')
| |
| − | **Less than or equal to 6 months ('''5 points''')
| |
| − | *Cytogenetics at diagnosis
| |
| − | **t(16;16) or inv(16) with or without additional cytogenetic abnormalities (0 points)
| |
| − | **t(8;21) with or without additional cytogenetic abnormalities ('''3 points''')
| |
| − | **Normal, intermediate, unfavorable, or unknown cytogenetics ('''5 points''')
| |
| − | *Age at time of first relapse
| |
| − | **Less than or equal to 35 years (0 points)
| |
| − | **36 to 45 years ('''1 point''')
| |
| − | **Greater than 45 years ('''2 points''')
| |
| − | *Stem cell transplantation performed before first relapse
| |
| − | **No (0 points)
| |
| − | **Yes, autologous or allogeneic ('''2 points''')
| |
| − | | |
| − | Risk stratification:
| |
| − | *'''1 to 6 points''': Favorable risk (1-year OS of 70%; 5-year OS of 46%)
| |
| − | *'''7 to 9 points''': Intermediate risk (1-year OS of 49%; 5-year OS of 18%)
| |
| − | *'''10 to 14 points''': Poor risk (1-year OS of 16%; 5-year OS of 4%)
| |
| − | | |
| − | ===References===
| |
| − | # Breems DA, Van Putten WL, Huijgens PC, Ossenkoppele GJ, Verhoef GE, Verdonck LF, Vellenga E, De Greef GE, Jacky E, Van der Lelie J, Boogaerts MA, Löwenberg B. Prognostic index for adult patients with acute myeloid leukemia in first relapse. J Clin Oncol. 2005 Mar 20;23(9):1969-78. Epub 2005 Jan 4. [http://jco.ascopubs.org/content/23/9/1969.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/15632409 PubMed]
| |
| − | | |
| − | ==Prognosis in cytogenetically normal AML==
| |
| − | # ''Seminal paper comparing the mutational status of NPM1, FLT3, CEBPA, MLL, and NRAS with clinical outcome:'' Schlenk RF, Döhner K, Krauter J, Fröhling S, Corbacioglu A, Bullinger L, Habdank M, Späth D, Morgan M, Benner A, Schlegelberger B, Heil G, Ganser A, Döhner H; German-Austrian Acute Myeloid Leukemia Study Group. Mutations and treatment outcome in cytogenetically normal acute myeloid leukemia. N Engl J Med. 2008 May 1;358(18):1909-18. [http://www.nejm.org/doi/full/10.1056/NEJMoa074306 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/18450602 PubMed]
| |
| − | | |
| − | =Investigational agents=
| |
| | | | |
| | + | = Investigational agents = |
| | ''These are drugs under study with at least some promising results for this disease.'' | | ''These are drugs under study with at least some promising results for this disease.'' |
| − | *[[Alvocidib (Flavopiridol)]]
| + | * [[Gilteritinib (ASP2215)]] |
| − | *[[Gilteritinib (ASP2215)]] | + | * [[Quizartinib (AC220)]] |
| − | *[[Vadastuximab talirine (SGN-CD33A)]] | |
| − | *[[Vosaroxin (SNS 595)]]
| |
| − | | |
| − | =Additional information=
| |
| − | | |
| − | ==Antifungal prophylaxis==
| |
| − | # Halpern AB, Lyman GH, Walsh TJ, Kontoyiannis DP, Walter RB. Primary antifungal prophylaxis during curative-intent therapy for acute myeloid leukemia. Blood. 2015 Dec 24;126(26):2790-7. Epub 2015 Oct 26. Review. [http://www.bloodjournal.org/content/126/26/2790.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4692139/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/26504183 PubMed]
| |
| − | | |
| | [[Category:Acute myeloid leukemia regimens]] | | [[Category:Acute myeloid leukemia regimens]] |
| − | [[Category:Disease-specific pages]] | + | [[Category:Biomarker-specific pages]] |
| | [[Category:Acute leukemias]] | | [[Category:Acute leukemias]] |
