title: Cloretazine (VNP40101M), a novel sulfonylhydrazine alkylating agent, in patients age 60 years or older with previously untreated acute myeloid leukemia.
abstract: OBJECTIVE
  Cloretazine (VNP40101M) is a sulfonylhydrazine alkylating agent with significant antileukemia activity. A multicenter phase II study of cloretazine was conducted in patients 60 years of age or older with previously untreated acute myeloid leukemia (AML) or high-risk myelodysplastic syndrome (MDS).
  
  
  METHODS
  Cloretazine 600 mg/m2 was administered as a single intravenous infusion. Patients were stratified by age, performance score, cytogenetic risk category, type of AML, and comorbidity.
  
  
  RESULTS
  One hundred four patients, median age 72 years (range, 60 to 84 years), were treated on study. Performance status was 2 in 31 patients (30%) and no patient had a favorable karyotype. Forty-seven patients (45%) had cardiac disease, 25 patients (24%) had hepatic disease, and 19 patients (18%) had pulmonary disease, defined as per the Hematopoietic Cell Transplantation-Specific Comorbidity Index, at study entry. The overall response rate was 32%, with 29 patients (28%) achieving complete response (CR) and four patients (4%) achieving CR with incomplete platelet recovery. Response rates in 44 de novo AML patients, 45 secondary AML patients, and 15 high-risk MDS patients were 50%, 11%, and 40%, respectively. Response by cytogenetic risk category was 39% in 56 patients with intermediate cytogenetic risk and 24% in 46 patients with unfavorable cytogenetic risk. Nineteen (18%) patients died within 30 days of receiving cloretazine therapy. Median overall survival was 94 days, with a 1-year survival of 14%; the median duration of survival was 147 days, with a 1-year survival of 28% for those who achieved CR.
  
  
  CONCLUSIONS
  Cloretazine has significant activity and modest extramedullary toxicity in elderly patients with AML or high-risk MDS. Response rates remain consistent despite increasing age and comorbidity.
authors.affiliation: The University of Texas M.D. Anderson Cancer Center, Department of Leukemia, Houston, TX 77030, USA. frankgiles@aol.com
authors.forename: Francis
authors.initials: F
authors.lastname: Giles
authors.forename: David
authors.initials: D
authors.lastname: Rizzieri
authors.forename: Judith
authors.initials: J
authors.lastname: Karp
authors.forename: Norbert
authors.initials: N
authors.lastname: Vey
authors.forename: Farhad
authors.initials: F
authors.lastname: Ravandi
authors.forename: Stefan
authors.initials: S
authors.lastname: Faderl
authors.forename: Khuda Dad
authors.initials: KD
authors.lastname: Khan
authors.forename: Gregor
authors.initials: G
authors.lastname: Verhoef
authors.forename: Pierre
authors.initials: P
authors.lastname: Wijermans
authors.forename: Anjali
authors.initials: A
authors.lastname: Advani
authors.forename: Gail
authors.initials: G
authors.lastname: Roboz
authors.forename: Hagop
authors.initials: H
authors.lastname: Kantarjian
authors.forename: Syed Fazl Ali
authors.initials: SF
authors.lastname: Bilgrami
authors.forename: Augustin
authors.initials: A
authors.lastname: Ferrant
authors.forename: Simon M G J
authors.initials: SM
authors.lastname: Daenen
authors.forename: Verena
authors.initials: V
authors.lastname: Karsten
authors.forename: Ann
authors.initials: A
authors.lastname: Cahill
authors.forename: Maher
authors.initials: M
authors.lastname: Albitar
authors.forename: Ghulam
authors.initials: G
authors.lastname: Mufti
authors.forename: Susan
authors.initials: S
authors.lastname: O'Brien
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D018906:Antineoplastic Agents, Alkylating / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D006834:Hydrazines / Q000009:adverse effects / Q000627:therapeutic use*; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D008956:Models, Chemical; D011379:Prognosis; D012074:Remission Induction; D012306:Risk; D013449:Sulfonamides / Q000009:adverse effects / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D018906:Antineoplastic Agents, Alkylating; D006834:Hydrazines; D013449:Sulfonamides; C483604:laromustine