| 1. |
|
|
| 2. |
- Levis, Mark, et al.
(författare)
-
Results from a randomized trial of salvage chemotherapy followed by lestaurtinib for patients with FLT3 mutant AML in first relapse
- 2011
-
Ingår i: Blood. - : American Society of Hematology. - 1528-0020 .- 0006-4971. ; 117:12, s. 3294-3301
-
Tidskriftsartikel (refereegranskat)abstract
- In a randomized trial of therapy for FMS-like tyrosine kinase-3 (FLT3) mutant acute myeloid leukemia in first relapse, 224 patients received chemotherapy alone or followed by 80 mg of the FLT3 inhibitor lestaurtinib twice daily. Endpoints included complete remission or complete remission with incomplete platelet recovery (CR/CRp), overall survival, safety, and tolerability. Correlative studies included pharmacokinetics and analysis of in vivo FLT3 inhibition. There were 29 patients with CR/CRp in the lestaurtinib arm and 23 in the control arm (26% vs 21%; P = .35), and no difference in overall survival between the 2 arms. There was evidence of toxicity in the lestaurtinib-treated patients, particularly those with plasma levels in excess of 20 mu M. In the lestaurtinib arm, FLT3 inhibition was highly correlated with remission rate, but target inhibition on day 15 was achieved in only 58% of patients receiving lestaurtinib. Given that such a small proportion of patients on this trial achieved sustained FLT3 inhibition in vivo, any conclusions regarding the efficacy of combining FLT3 inhibition with chemotherapy are limited. Overall, lestaurtinib treatment after chemotherapy did not increase response rates or prolong survival of patients with FLT3 mutant acute myeloid leukemia in first relapse. This study is registered at www.clinicaltrials.gov as #NCT00079482. (Blood. 2011;117(12): 3294-3301)
|
|
| 3. |
- Ottmann, Oliver, et al.
(författare)
-
Dasatinib induces rapid hematologic and cytogenetic responses in adult patients with Philadelphia chromosome-positive acute lymphoblastic leukemia with resistance or intolerance to imatinib : interim results of a phase 2 study
- 2007
-
Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 110:7, s. 2309-2315
-
Tidskriftsartikel (refereegranskat)abstract
- Patients with Philadelphia (Ph) chromosome-positive acute lymphoblastic leukemia (ALL) have a rapid disease course and a poor prognosis. Dasatinib, a novel, oral, multitargeted kinase inhibitor of BCR-ABL and SRC family kinases, has previously induced responses in patients with imatinib-resistant or -intolerant Ph-positive ALL. We present the interim results of a phase 2 study designed to further assess the efficacy, safety, and tolerability of dasatinib 140 mg in this patient population (n = 36). With a minimum follow-up of 8 months, treatment with dasatinib resulted in substantial hematologic and cytogenetic response rates. Major hematologic responses were achieved in 42% (15/36) of patients, 67% of whom remained progression-free. Complete cytogenetic responses were attained by 58% (21/36) of patients. The presence of BCR-ABL mutations conferring imatinib resistance did not preclude a response to dasatinib. Dasatinib was also tolerable, with 6% (2/36) of patients discontinuing therapy as a result of study-drug toxicity. Most adverse events (AEs) were grade 1 or 2; febrile neutropenia was the most frequent severe AE, but this and other cytopenias were manageable with dose reduction. Dasatinib represents a safe and effective treatment option and an important therapeutic advance for patients with Ph-positive ALL. This trial was registered at www.clinicaltrials.gov as #CA180015.
|
|
