Efficacy of imatinib dose escalation in patients with chronic myeloid leukemia in chronic phase
Hagop M Kantarjian, Richard A Larson, Francois Guilhot, Stephen G O'Brien, Manisha Mone, Marc Rudoltz, Tillmann Krahnke, Jorge Cortes, Brian J Druker, International Randomized Study of Interferon and STI571 (IRIS) Investigators, S Durant, A Schwarer, D Joske, J Seymour, A Grigg, D Ma, C Arthur, K Bradstock, D Joshua, A Louwagi, P Martiat, A Bosly, C Shistok, J Lipton, D Forrest, I Walker, D C Roy, M Rubinger, I Bence-Bruckler, D Stewart, M Kovacs, A R Turner, H Birgens, O Bjerrum, T Facon, J L Harousseau, M Tulliez, A Guerci, D Blaise, F Maloisel, M Michallet, R Andreesen, C Nerl, M Freund, N Gattermann, G Ehninger, M Deininger, O Ottmann, C Peschel, S Fruehauf, A Neubauer, P le Coutre, W Aulitzky, R Fanin, G Rosti, F Mandelli, M Lazzarino, E Morra, A Carella, M Petrini, F Nobile, V Liso, F Ferrara, V Rizzoli, G Fiortoni, G Martinelli, G Ossenkoppele, P Browett, T Gedde-Dahl, J M Tangen, I Dahl, J Odrizoala, J C Hernandez Boulda, J L Steegman, C Canizo, J Diaz, A Grenena, M N Fernandez, L Stenke, C Paul, M Bjoreman, C Malm, H Wadenvik, P G Nilsson, I Turesson, U Hess, M Solenthaler, R E Clark, A R Green, T L Holyoake, G S Lucas, G Smith, D W Milligan, S J Rule, A K Burnett, R Moroose, M Wetzler, J Bearden, S Cataland, I Robinowitz, B Meisenberg, K Thompson, S Graziano, P Emanuel, H Gross, P Cobb, R Bhatia, S Dakhil, D Irwin, B Issell, S Pavletic, P Kuebler, E Layhe, P Butra, J Glass, J Moore, B Grant, H Neill, R Herzig, H Burris, B Petersen, M Kalaycio, D Stirewalt, W Samlowski, E Berman, S Limentani, T Seay, T Shea, L Akard, G Smith, P Becker, S Devine, R Hart, R Veith, J Wade, M Brunvad, L Kalman, D Strickland, M Shurafa, A Bashey, R Shadduck, H Safah, M Rubenstein, R Collins, A Keller, M Tallman, A Pecora, M Agha, H Homes, R Guidice, V Santini, Hagop M Kantarjian, Richard A Larson, Francois Guilhot, Stephen G O'Brien, Manisha Mone, Marc Rudoltz, Tillmann Krahnke, Jorge Cortes, Brian J Druker, International Randomized Study of Interferon and STI571 (IRIS) Investigators, S Durant, A Schwarer, D Joske, J Seymour, A Grigg, D Ma, C Arthur, K Bradstock, D Joshua, A Louwagi, P Martiat, A Bosly, C Shistok, J Lipton, D Forrest, I Walker, D C Roy, M Rubinger, I Bence-Bruckler, D Stewart, M Kovacs, A R Turner, H Birgens, O Bjerrum, T Facon, J L Harousseau, M Tulliez, A Guerci, D Blaise, F Maloisel, M Michallet, R Andreesen, C Nerl, M Freund, N Gattermann, G Ehninger, M Deininger, O Ottmann, C Peschel, S Fruehauf, A Neubauer, P le Coutre, W Aulitzky, R Fanin, G Rosti, F Mandelli, M Lazzarino, E Morra, A Carella, M Petrini, F Nobile, V Liso, F Ferrara, V Rizzoli, G Fiortoni, G Martinelli, G Ossenkoppele, P Browett, T Gedde-Dahl, J M Tangen, I Dahl, J Odrizoala, J C Hernandez Boulda, J L Steegman, C Canizo, J Diaz, A Grenena, M N Fernandez, L Stenke, C Paul, M Bjoreman, C Malm, H Wadenvik, P G Nilsson, I Turesson, U Hess, M Solenthaler, R E Clark, A R Green, T L Holyoake, G S Lucas, G Smith, D W Milligan, S J Rule, A K Burnett, R Moroose, M Wetzler, J Bearden, S Cataland, I Robinowitz, B Meisenberg, K Thompson, S Graziano, P Emanuel, H Gross, P Cobb, R Bhatia, S Dakhil, D Irwin, B Issell, S Pavletic, P Kuebler, E Layhe, P Butra, J Glass, J Moore, B Grant, H Neill, R Herzig, H Burris, B Petersen, M Kalaycio, D Stirewalt, W Samlowski, E Berman, S Limentani, T Seay, T Shea, L Akard, G Smith, P Becker, S Devine, R Hart, R Veith, J Wade, M Brunvad, L Kalman, D Strickland, M Shurafa, A Bashey, R Shadduck, H Safah, M Rubenstein, R Collins, A Keller, M Tallman, A Pecora, M Agha, H Homes, R Guidice, V Santini
Abstract
Background: Imatinib mesylate given orally at a daily dose of 400 mg is the standard of care as initial therapy for patients with chronic myeloid leukemia (CML) in chronic phase (CML-CP). Treatment guidelines propose dose escalation based on clinical assessments of disease response.
Methods: Response and survival were analyzed in a cohort of patients (n = 106) with newly diagnosed CML-CP who were enrolled on the International Randomized Study of Interferon and STI571 (IRIS) trial, who began treatment with imatinib at a dose of 400 mg daily, and who subsequently underwent dose escalation to either 600 mg or 800 mg daily. Reasons for dose escalation were evaluated retrospectively based on 2 sets of criteria: the IRIS protocol-defined criteria (n = 39 patients) and the European LeukemiaNet (ELN) recommendations (n = 48 patients).
Results: Among all 106 patients who underwent dose escalation, the rates of freedom from progression to accelerated phase or blast phase and overall survival were 89% and 84% at 3 years after dose increase, respectively. A cytogenetic response was obtained in 42% of patients who had their dose escalated based on protocol criteria and in 38% of patients who had their dose escalated according to the ELN recommendations.
Conclusions: The results from this retrospective analysis supported imatinib dose escalation as an appropriate initial option for patients with CML-CP who were experiencing suboptimal cytogenetic response or resistance.
Trial registration: ClinicalTrials.gov NCT00006343.
(c) 2008 American Cancer Society.
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Source: PubMed