Phase 2 clinical trial of 5-azacitidine, valproic acid, and alltrans retinoic acid in patients with high-risk acute myeloid leukemia or myelodysplastic syndrome

Oncotarget

Volumn 1, Issue 1, 2010, Pages 34-42

  Raffoux, Emmanuel ^a   Cras, Audrey ^b   Recher, Christian ^c   Boëlle, Pierre Yves ^d   de Labarthe, Adrienne ^a   Turlure, Pascal ^e   Marolleau, Jean Pierre ^f   Reman, Oumedaly ^g   Gardin, Claude ^h   Victor, Maud ^b   Maury, Sébastien ⁱ   Rousselot, Philippe ^j   Malfuson, Jean Valère ^k   Maarek, Odile ^a   Daniel, Marie Thérèse ^a   Fenaux, Pierre ^h   Degos, Laurent ^a   Chomienne, Christine ^b   Chevret, Sylvie ^a   Dombret, Hervé ^a  

^a SAINT LOUIS HOSPITAL   (France)

^b UNIVERSITÉ PARIS DIDEROT   (France)

^c CHU PURPAN   (France)

^d HÔPITAL SAINT ANTOINE   (France)

^e DUPUYTREN UNIVERSITY HOSPITAL   (France)

^f AMIENS UNIVERSITY HOSPITAL   (France)

^g CAEN UNIVERSITY HOSPITAL   (France)

^h AVICENNE HOSPITAL   (France)

ⁱ HENRI MONDOR HOSPITAL   (France)

^j Département d'Hématologie   (France)

^k PERCY MILITARY HOSPITAL   (France)

more..

Author keywords

Acute myeloid leukemia; ATRA; Azacitidine; FZD9 methylation; Valproic acid

Indexed keywords

AZACITIDINE; RETINOIC ACID; VALPROIC ACID; ANTICONVULSIVE AGENT; ANTINEOPLASTIC AGENT; DNA;

ACUTE MYELOBLASTIC LEUKEMIA; ADULT; AGED; ALOX12 GENE; ARTICLE; ASPERGILLOSIS; BLEEDING; CALCA GENE; CANCER GROWTH; CANCER RECURRENCE; CANCER RISK; COHORT ANALYSIS; CONFUSION; CONSTIPATION; CONTROLLED STUDY; DEMETHYLATION; DRUG EFFICACY; DRUG SAFETY; DRUG TOLERABILITY; EPIGENETICS; FATIGUE; FEMALE; FZD9 GENE; GENE; GENETIC ASSOCIATION; HPN GENE; HUMAN; IN VITRO STUDY; IN VIVO STUDY; INFECTION; INJECTION SITE REACTION; KARYOTYPE; MAJOR CLINICAL STUDY; MALE; MUCOSAL DRYNESS; MULTIPLE CYCLE TREATMENT; MYELODYSPLASTIC SYNDROME; NAUSEA; OVERALL SURVIVAL; PHASE 2 CLINICAL TRIAL; PNEUMONIA; PROSPECTIVE STUDY; SEPTICEMIA; SOMNOLENCE; SUBCUTANEOUS PUNCTURE SITE REACTION; TREATMENT RESPONSE; VOMITING; ACUTE GRANULOCYTIC LEUKEMIA; CLINICAL TRIAL; DNA METHYLATION; GENETICS; MIDDLE AGED; MULTICENTER STUDY; POLYMERASE CHAIN REACTION; SURVIVAL RATE; TREATMENT OUTCOME;

AGED; AGED, 80 AND OVER; ANTICONVULSANTS; ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS; AZACITIDINE; DNA METHYLATION; DNA, NEOPLASM; EPIGENOMICS; FEMALE; HUMANS; LEUKEMIA, MYELOID, ACUTE; MALE; MIDDLE AGED; MYELODYSPLASTIC SYNDROMES; POLYMERASE CHAIN REACTION; SURVIVAL RATE; TREATMENT OUTCOME; TRETINOIN; VALPROIC ACID;

EID: 84855487228     PISSN: None     EISSN: 19492553     Source Type: Journal    
DOI: 10.18632/oncotarget.106     Document Type: Article

References (25)

1. Herman JG, Baylin SB. Mechanisms of disease: gene silencing in cancer in association with promoter hypermethylation. N Engl J Med 2003; 349:2042-2054.
2. Silverman LR, Demakos EP, Peterson BL, Kornblith AB, Holland JC, Odchimar-Reissig R, Stone RM, Nelson D, Powell BL, DeCastro CM, Ellerton J, Larson RA, Schiffer CA, Holland JF. Randomized controlled trial of azacitidine in patients with the myelodysplastic syndrome: a study of the cancer and leukemia group B. J Clin Oncol 2002;20:2429- 2440.
3. Sudan N, Rossetti JM, Shadduck RK, Latsko J, Lech JA, Kaplan RB, Kennedy M, Gryn JF, Faroun Y, Lister J. Treatment of acute myelogenous leukemia with outpatient azacitidine. Cancer 2006;107:1839-1843.
4. Cashen AF, Schiller GJ, O'Donnell MR, Larsen JS, Baranwal A, DiPersio JF. Preliminary results of a multicenter Phase II trial of 5-day decitabine as front-line therapy for elderly patients with acute myeloid leukemia. Blood 2008 (ASH Meeting Abstracts);112:560.
5. Lübbert M, Schmid M, Rüter B, Germing U, Rethwisch V, Ganser A, Platzbecker U, Galm O, Brugger W, Wijermans PW, Schmoor C, Döhner H. Continued treatment with an outpatient maintenance schedule of decitabine in older AML patients ineligible for induction chemotherapy: results of the Phase II multicenter trial. Blood 2008 (ASH Meeting Abstracts);112:2965.
6. Blum W, Klisovic R, Liu S,Garzon R, Kefauver C, Liu Z, Mickle J, Devine H, Devine S, Grever MR, Chan K, Villalona-Calero M, Byrd JC, Marcucci G. Preliminary results of a Phase II study of low dose decitabine as a single agent in older patients (age=60) with previously untreated acute myeloid leukemia. Blood 2008 (ASH Meeting Abstracts);112:2957.
7. Al-Hali HK. The safety and efficacy of azacitidine in patients with newly-diagnosed and refractory/relapsed AML not eligible for or resistant to chemotherapy: a multicenter Phase I/II study of the East German Haematology and Oncology Study Group (OSHO). Haematologica 2009 (EHA Meeting Abstracts);94:343.
8. Fenaux P, Mufti GJ, Hellstrom-Lindberg E, Santini V, Finelli C, Giagounidis A, Schoch R, Gattermann N, Sanz G, List A, Gore SD, Seymour JF, Bennett JM, Byrd J, Backstrom J, Zimmerman L, McKenzie D, Beach C, Silverman LR; International Vidaza High-Risk MDS Survival Study Group. Efficacy of azacitidine compared with that of conventional care regimens in the treatment of higher-risk myelodysplastic syndromes: a randomized open-label Phase III study. Lancet Oncol 2009 ;10 :223-232.
9. Fenaux P, Mufti GJ, Hellström-Lindberg E, Santini V, Gattermann N, Germing U, Sanz G, List AF, Gore S, Seymour JF, Dombret H, Backstrom J, Zimmerman L, McKenzie D, Beach CL, Silverman LR. Azacitidine improves overall survival in WHO acute myeloid leukemia in elderly patients with low bone marrow blast count. J Clin Oncol. 2010 ;28:562-569.
10. Kitaruma K, Hoshi S, Koike M, Kiyoi H, Saito H, Naoe T. Histone deacetylase inhibitor but not arsenic trioxide differentiates acute promyelocytic leukaemia cells with t(11;17) in combination with all-trans retinoic acid. Br J Haematol 2000;108:696-702.
11. Warrell RP Jr, He LZ, Richon V, Calleja E, Pandolfi PP. Therapeutic targeting of transcription in acute promyelocytic leukemia by use of an inhibitor of histone deacetylase. J Nat Cancer Inst 1998;90:1621-1625.
12. Phiel CJ, Zhang F, Huang EY, Guenther MG, Lazar MA, Klein PS. Histone deacetylase is a direct target of valproic acid, a potent anticonvulsant, mood stabilizer, and teratogen. J Biol Chem 2001;276:36734-36741.
13. Kuendgen A, Strupp C, Aivado M, Bernhardt A, Hildebrandt B, Haas R, Germing U, Gattermann N. Treatment of myelodysplastic syndromes with valproic acid alone or in combination with all-trans retinoic acid. Blood 2004;104:1266-1269.
14. Raffoux E, Chaibi P, Dombret H, Degos L. Valproic acid and all-trans retinoic acid for the treatment of elderly patients with acute myeloid leukemia. Haematologica 2005;90:986- 988.
15. Greenberg P, Cox C, LeBeau MM, Fenaux P, Morel P, Sanz G, Vallespi T, Hamblin T, Oscier D, Ohyashiki K, Toyama K, Aul C, Mufti G, Bennett J. International scoring system for evaluating prognosis in myelodysplastic syndromes. Blood 1997;89:2079-2088.
16. Cheson BD, Bennett JM, Kopecky KJ, Bûchner T, William 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.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;21:4642- 4649.
17. Cheson BD, Greenberg PL, Bennett JM, Lowenberg B, Wijermans PW, Nimer SD, Pinto A, Beran M, de Witte TM, Stone RM, Mittelman M, Sanz GF, Gore SD, Schiffer CA, Kantarjian H. Clinical application and proposal for modification of the International Working Group (IWG) response criteria in myelodysplasia. Blood 2006;108:419-425.
18. Soriano AO, Yang H, Faderl S, Estrov Z, Giles F, Ravandi F, Cortes J, Wierda WG, Ouzounian S, Quezada A, Pierce S, Estey EH, Issa JP, Kantarjian HM, Garcia-Manero G. Safety and clinical activity of the combination of 5-azacitidine, valproic acid, and all-trans retinoic acid in patients with acute myeloid leukemia and myelodysplastic syndrome. Blood 2007;110:2302-2308.
19. Craddock C, Goardon N, Griffiths M, Siddique S, Cavenagh J, Vyas P. 5' azacitidine in combination with valproic acid induces complete remissions in patients with high risk acute myeloid leukaemia but does not eradicate clonal leukaemic stem/progenitor cells. Haematologica 2009 (EHA Meeting Abstracts);94:429.
20. 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, 108: 3271-3279.
21. Yang H, Hoshino K, Sanchez-Gonzalez B, Kantarjian H, Garcia-Manero G. Antileukemia activity of the combination of 5-aza-2'-deoxycytidine with valproic acid. Leukemia Research 2005;29:739-748.
22. Issa JP, Castoro R, Ravandi-Kashani F, Faderl S, Huang X, Estey E, Borthakur G, Morris G, Garcia-Manero G, Kantarjian H. Randomized Phase II study of combined epigenetic therapy: decitabine vs. decitabine and valproic acid in MDS and AML. Blood 2008 (ASH Annual Meeting Abstracts);112:228.
23. Silverman LR, Verma A, Odchimar-Reissig R, LeBlanc A, Najfeld V, Gabrilove J, Isola L, Espinoza_Delgado I, Zwiebel J. A phase I trial of epigenetic modulators vorinostat, in combination with azacitidine (azaC) in patients with the myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML): a study of the New York Cancer Consortium. Blood (ASH Annual Meeting Abstracts);112:3656.
24. Fandy TE, Herman JG, Kerns P, Jiemjit A, Sugar EA, Choi SH, Yang AS, Aucott T, Dauses T, Odchimar-Reissig R, Licht J, McConnell MJ, Nasrallah C, Kim MK, Zhang W, Sun Y, Murgo A, Espinoza-Delgado I, Oteiza K, Owoeye I, Silverman LR, Gore SD, Carraway HE. Early epigenetic changes and DNA damage do not predict clinical response in an overlapping schedule of 5-azacitidine and entinostat in patients with myeloid malignancies. Blood 2009;114:3448-3458.
25. Jiang Y, Dunbar A, Gondek L.P, Mohan S, Rataul M, O'Keefe C, Sekeres M, Saunthararajah Y, Maciejewski JP.Aberrant DNA methylation is a dominant mechanism in MDS progression to AML. Blood 2009;113:1315-1325.