Steven Coutre

Publication Details

  • Results from a randomized trial of salvage chemotherapy followed by lestaurtinib for patients with FLT3 mutant AML in first relapse BLOOD Levis, M., Ravandi, F., Wang, E. S., Baer, M. R., Perl, A., Coutre, S., Erba, H., Stuart, R. K., Baccarani, M., Cripe, L. D., Tallman, M. S., Meloni, G., Godley, L. A., Langston, A. A., Amadori, S., Lewis, I. D., Nagler, A., Stone, R., Yee, K., Advani, A., Douer, D., Wiktor-Jedrzejczak, W., Juliusson, G., Litzow, M. R., Petersdorf, S., Sanz, M., Kantarjian, H. M., Sato, T., Tremmel, L., Bensen-Kennedy, D. M., Small, D., Smith, B. D. 2011; 117 (12): 3294-3301

    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 ?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.

    View details for DOI 10.1182/blood-2010-08-301796

    View details for Web of Science ID 000288848500012

    View details for PubMedID 21270442

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