Evaluation of in vivo antineoplastic effects of rapamycin in patients with chemotherapy-refractory AML.
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.
Boehm
Alexandra
A
Department of Internal Medicine I, Division of Hematology & Hemostaseology, Medical University of Vienna, Austria.
Mayerhofer
Matthias
M
Herndlhofer
Susanne
S
Knoebl
Paul
P
Sillaber
Christian
C
Sperr
Wolfgang R
WR
Jaeger
Ulrich
U
Valent
Peter
P
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
D000903:Antibiotics, Antineoplastic; D000970:Antineoplastic Agents; D020123:Sirolimus; D006918:Hydroxyurea