title: Phase I-II study of bendamustine in patients with acute leukemia and high risk myelodysplastic syndrome.
abstract: A phase I-II study of bendamustine fractionated twice daily schedule for 4 days identified 75 mg/m(2) intravenously(IV) twice daily for 4 days as a phase II study schedule.
  
  
  BACKGROUND
  Alkylating agents have shown activity in leukemia. Bendamustine, an active alkylating agent in lymphoma and chronic lymphocytic leukemia, was given in a fractionated twice daily schedule for 4 days to patients with acute leukemia and myelodysplastic syndrome (MDS) to define the dose-limiting toxicities (DLT) and maximum tolerated dose (MTD).
  
  
  METHODS
  Adults with refractory acute leukemia or high-risk MDS were treated with bendamustine at a starting dose of 50 mg/m(2) IV over 1-2 hours twice daily for 4 days. Dose escalations were by 25 mg/m(2) in the 1st 3 levels. The study used the 3 + 3 design.
  
  
  RESULTS
  A total of 25 patients were treated. Their median age was 57 years; the median salvage number was 3. Grade 2 creatinine elevations were observed in 1 of 6 patients at the 50 mg/m(2) dose, in 2 of 13 patients at the 75 mg/m(2) dose, and in 3 of 6 patients at the 100 mg/m(2) dose. This was considered significant, even though DLT was not reached. One patient achieved marrow complete remission. Significant reductions of marrow blasts (50% or more) were observed in 6 of 25 patients (24%).
  
  
  CONCLUSIONS
  Bendamustine fractionated dose level of 100 mg/m(2) IV twice daily for 4 days (800 mg/m(2) per course) was associated with Grade 2 renal toxicity. The proposed phase II schedule is 75 mg/m(2) IV twice daily for 4 days. Future studies should evaluate this schedule in less heavily treated patients.
authors.affiliation: The Department of Leukemia, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Christelle
authors.initials: C
authors.lastname: Chacar
authors.forename: Elias
authors.initials: E
authors.lastname: Jabbour
authors.forename: Farhad
authors.initials: F
authors.lastname: Ravandi
authors.forename: Gautam
authors.initials: G
authors.lastname: Borthakur
authors.forename: Tapan
authors.initials: T
authors.lastname: Kadia
authors.forename: Zeev
authors.initials: Z
authors.lastname: Estrov
authors.forename: Mary Beth
authors.initials: MB
authors.lastname: Rios
authors.forename: Jorge
authors.initials: J
authors.lastname: Cortes
authors.forename: Hagop
authors.initials: H
authors.lastname: Kantarjian
mesh_terms: D000208:Acute Disease; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000069461:Bendamustine Hydrochloride; D005260:Female; D006801:Humans; D007938:Leukemia / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000188:drug therapy*; D009588:Nitrogen Mustard Compounds / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D018906:Antineoplastic Agents, Alkylating; D009588:Nitrogen Mustard Compounds; D000069461:Bendamustine Hydrochloride