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Temsirolimus, an mTOR inhibitor, in combination with lower-dose clofarabine as salvage therapy for older patients with acute myeloid leukaemia: results of a phase II GIMEMA study (AML-1107).
- Source :
-
British journal of haematology [Br J Haematol] 2012 Jan; Vol. 156 (2), pp. 205-12. Date of Electronic Publication: 2011 Nov 15. - Publication Year :
- 2012
-
Abstract
- The mammalian target of rapamycin (mTOR) signalling pathway has emerged as an important therapeutic target for acute myeloid leukaemia (AML). This study assessed the combination of temsirolimus, an mTOR inhibitor, and lower-dose clofarabine as salvage therapy in older patients with AML. Induction consisted of clofarabine 20mg/m(2) on days 1-5 and temsirolimus 25mg (flat dose) on days 1, 8 and 15. Patients achieving complete remission with (CR) or without (CRi) full haematological recovery could receive monthly temsirolimus maintenance. In 53 evaluable patients, the overall remission rate (ORR) was 21% (8% CR, 13% CRi). Median disease-free survival was 3·5months, and median overall survival was 4months (9·1months for responders). The most common non-haematological severe adverse events included infection (48%), febrile neutropenia (34%) and transaminitis (11%). The 30-d all-cause induction mortality was 13%. Laboratory data from 25 patients demonstrated that a >50%in vivo inhibition of S6 ribosomal protein phosphorylation was highly correlated with response rate (75% with inhibition versus 0% without inhibition; P=0·0001), suggesting that targeting the mTOR pathway is clinically relevant. The acceptable safety profile and the predictive value of target inhibition encourage further investigation of this novel regimen.<br /> (© 2011 Blackwell Publishing Ltd.)
- Subjects :
- Adenine Nucleotides administration & dosage
Adenine Nucleotides adverse effects
Age Factors
Aged
Antineoplastic Combined Chemotherapy Protocols adverse effects
Arabinonucleosides administration & dosage
Arabinonucleosides adverse effects
Clofarabine
Disease-Free Survival
Female
Humans
Male
Middle Aged
Sirolimus administration & dosage
Sirolimus adverse effects
Sirolimus analogs & derivatives
TOR Serine-Threonine Kinases antagonists & inhibitors
Antineoplastic Combined Chemotherapy Protocols therapeutic use
Leukemia, Myeloid, Acute drug therapy
Salvage Therapy methods
Subjects
Details
- Language :
- English
- ISSN :
- 1365-2141
- Volume :
- 156
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- British journal of haematology
- Publication Type :
- Academic Journal
- Accession number :
- 22082314
- Full Text :
- https://doi.org/10.1111/j.1365-2141.2011.08940.x