title: Evaluation of in vivo antineoplastic effects of rapamycin in patients with chemotherapy-refractory AML.
abstract: BACKGROUND
  The mammalian target of rapamycin (mTOR) has recently been identified as a potential target in acute myeloid leukemia (AML).
  
  
  METHODS
  We treated 5 patients with chemotherapy-refractory AML with the mTOR-inhibitor rapamycin at 2mg per os daily for 14 days, with dose adjustment allowed to reach a target serum rapamycin concentration of 10-20 ng/mL. Four of five patients received additional hydroxyurea at constant dose during treatment with rapamycin.
  
  
  RESULTS
  Two patients achieved a leukocyte response, in one of them, a prolonged response was seen. In the other patients, blast counts remained stable or increased during rapamycin therapy. We did not observe severe hematologic or non-hematologic side effects of rapamycin.
  
  
  CONCLUSIONS
  Rapamycin at 2mg per day acts mildly cytoreductive in a subgroup of patients with refractory AML. Higher doses and drug combinations may be required to obtain long lasting anti-leukemic effects in these patients.
authors.affiliation: Department of Internal Medicine I, Division of Hematology & Hemostaseology, Medical University of Vienna, Austria.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Boehm
authors.forename: Matthias
authors.initials: M
authors.lastname: Mayerhofer
authors.forename: Susanne
authors.initials: S
authors.lastname: Herndlhofer
authors.forename: Paul
authors.initials: P
authors.lastname: Knoebl
authors.forename: Christian
authors.initials: C
authors.lastname: Sillaber
authors.forename: Wolfgang R
authors.initials: WR
authors.lastname: Sperr
authors.forename: Ulrich
authors.initials: U
authors.lastname: Jaeger
authors.forename: Peter
authors.initials: P
authors.lastname: Valent
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols; D005260:Female; D006801:Humans; D006918:Hydroxyurea / Q000008:administration & dosage / Q000627:therapeutic use; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy*; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D020123:Sirolimus / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000903:Antibiotics, Antineoplastic; D000970:Antineoplastic Agents; D020123:Sirolimus; D006918:Hydroxyurea