title: Outpatient bendamustine and idarubicin for upfront therapy of elderly acute myeloid leukaemia/myelodysplastic syndrome: a phase I/II study using an innovative statistical design.
abstract: Combinations of agents may improve outcomes among elderly acute myeloid leukaemia (AML) and high-risk myelodysplastic syndrome (MDS) patients. We performed an adaptive phase I/II trial for newly-diagnosed AML or high-risk MDS patients aged ≥50 years using a Bayesian approach to determine whether 1 of 3 doses of bendamustine (45, 60, 75 mg/m(2) days 1-3), together with idarubicin (12 mg/m(2) days 1-2), might provide a complete response (CR) rate ≥40% with <30% grade 3-4 non-haematological toxicity. We treated 39 patients (34 AML; five MDS with >10% marrow blasts; median age 73 years). None of the three bendamustine doses in combination with idarubicin met the required CR and toxicity rates; the 75 mg/m(2) dose because of excess toxicity (two of three patients) and the 60 mg/m(2) dose because of low efficacy (CR rate 10/33), although no grade 3-4 non-haematological toxicity was seen at this dose. Median survival was 7·2 months. All patients began treatment as outpatients but hospitalization was required in 90% (35/39). Although we did not find a dose of bendamustine combined with idarubicin that would provide a CR rate of >40% with acceptable toxicity, bendamustine may have activity in AML/MDS patients, suggesting its addition to other regimens may be warranted.
authors.affiliation: Saint Louis University, Saint Louis, MO, USA.
authors.forename: Jack M
authors.initials: JM
authors.lastname: Lionberger
authors.forename: John M
authors.initials: JM
authors.lastname: Pagel
authors.forename: Vicky K
authors.initials: VK
authors.lastname: Sandhu
authors.forename: Hu
authors.initials: H
authors.lastname: Xie
authors.forename: Mazyar
authors.initials: M
authors.lastname: Shadman
authors.forename: Raya
authors.initials: R
authors.lastname: Mawad
authors.forename: Alexandra
authors.initials: A
authors.lastname: Boehm
authors.forename: Carol
authors.initials: C
authors.lastname: Dean
authors.forename: Kathleen
authors.initials: K
authors.lastname: Shannon-Dorcy
authors.forename: Bart L
authors.initials: BL
authors.lastname: Scott
authors.forename: Hans Joachim
authors.initials: HJ
authors.lastname: Deeg
authors.forename: Pamela S
authors.initials: PS
authors.lastname: Becker
authors.forename: Paul C
authors.initials: PC
authors.lastname: Hendrie
authors.forename: Roland B
authors.initials: RB
authors.lastname: Walter
authors.forename: Fabiana
authors.initials: F
authors.lastname: Ostronoff
authors.forename: Frederick R
authors.initials: FR
authors.lastname: Appelbaum
authors.forename: Elihu H
authors.initials: EH
authors.lastname: Estey
mesh_terms: D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D000069461:Bendamustine Hydrochloride; D015331:Cohort Studies; D005260:Female; D006760:Hospitalization; D006801:Humans; D015255:Idarubicin / Q000008:administration & dosage; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000188:drug therapy*; D009588:Nitrogen Mustard Compounds / Q000008:administration & dosage; D010045:Outpatients; D016896:Treatment Outcome
chemical_list: D009588:Nitrogen Mustard Compounds; D000069461:Bendamustine Hydrochloride; D015255:Idarubicin
keywords: Bayesian; acute myeloid leukaemia; bendamustine; elderly; myelodysplastic syndrome
references.citation: Clin Lymphoma Myeloma. 2008 Aug;8 Suppl 4:S128-36
references.pmid: 18952543
references.citation: J Natl Compr Canc Netw. 2012 Aug;10(8):984-1021
references.pmid: 22878824
references.citation: Semin Hematol. 2008 Jul;45(3 Suppl 2):S7-10
references.pmid: 18760709
references.citation: J Clin Oncol. 2009 Mar 20;27(9):1492-501
references.pmid: 19224851
references.citation: Blood. 2003 Jul 15;102(2):442-8
references.pmid: 12560224
references.citation: Br J Haematol. 2006 Oct;135(2):165-73
references.pmid: 16939487
references.citation: Blood. 2010 Oct 7;116(14):2420-8
references.pmid: 20538802
references.citation: Blood. 2005 Aug 15;106(4):1154-63
references.pmid: 15870183
references.citation: Leuk Lymphoma. 2007 Jun;48(6):1161-6
references.pmid: 17577779
references.citation: Stat Med. 2008 Jul 10;27(15):2802-15
references.pmid: 17948869
references.citation: Blood. 2006 May 1;107(9):3481-5
references.pmid: 16455952
references.citation: J Clin Oncol. 2003 Dec 15;21(24):4642-9
references.pmid: 14673054
references.citation: Hematology Am Soc Hematol Educ Program. 2004;:98-117
references.pmid: 15561679
references.citation: Hematology Am Soc Hematol Educ Program. 2003;:82-101
references.pmid: 14633778
references.citation: J Clin Oncol. 2011 Nov 20;29(33):4417-23
references.pmid: 21969499
references.citation: Blood. 2000 Dec 15;96(13):4075-83
references.pmid: 11110676