PURPOSE OF REVIEW: Imatinib was registered several years ago for the treatment of chronic-phase chronic myeloid leukemia. Because of the occurrence of resistance with imatinib, new drugs have been developed recently, two of which, nilotinib and dasatinib, are being registered for frontline therapy. However physicians may be confused as to how to treat and manage their newly diagnosed patients. The value of new scoring systems and well known surrogate markers such as cytogenetic and molecular responses as well as recent data from phase II or III trials are presented and discussed. RECENT FINDINGS: The analysis of trials comparing 400 mg of imatinib to higher doses suggests that 400 mg still seems to be the appropriate initial dose. However, doses of 800 mg could be proposed for high-risk patients or for those with slower response. Sokal and Euro scoring systems are useful and should be calculated before initiating the treatment. The achievement of early complete cytogenetic response is still a valid surrogate marker, although close molecular monitoring is also mandatory. Second-generation tyrosine kinase inhibitors have proved their efficacy by reducing the rate of progression to advanced phases. SUMMARY: Long-term follow-up of ongoing trials investigating tyrosine kinase inhibitors, alone or in combination with interferon, will assess their efficacy on overall survival.
PURPOSE OF REVIEW: Imatinib was registered several years ago for the treatment of chronic-phase chronic myeloid leukemia. Because of the occurrence of resistance with imatinib, new drugs have been developed recently, two of which, nilotinib and dasatinib, are being registered for frontline therapy. However physicians may be confused as to how to treat and manage their newly diagnosed patients. The value of new scoring systems and well known surrogate markers such as cytogenetic and molecular responses as well as recent data from phase II or III trials are presented and discussed. RECENT FINDINGS: The analysis of trials comparing 400 mg of imatinib to higher doses suggests that 400 mg still seems to be the appropriate initial dose. However, doses of 800 mg could be proposed for high-risk patients or for those with slower response. Sokal and Euro scoring systems are useful and should be calculated before initiating the treatment. The achievement of early complete cytogenetic response is still a valid surrogate marker, although close molecular monitoring is also mandatory. Second-generation tyrosine kinase inhibitors have proved their efficacy by reducing the rate of progression to advanced phases. SUMMARY: Long-term follow-up of ongoing trials investigating tyrosine kinase inhibitors, alone or in combination with interferon, will assess their efficacy on overall survival.
Authors: Frank S Ong; Kingshuk Das; Jay Wang; Hana Vakil; Jane Z Kuo; Wendell-Lamar B Blackwell; Stephen W Lim; Mark O Goodarzi; Kenneth E Bernstein; Jerome I Rotter; Wayne W Grody Journal: Expert Rev Mol Diagn Date: 2012-07 Impact factor: 5.225
Authors: Vinícius Marcondes Rezende; Ariane Julio Rivellis; Melissa Medrano Gomes; Felipe Augusto Dörr; Mafalda Megumi Yoshinaga Novaes; Luciana Nardinelli; Ariel Lais de Lima Costa; Dalton de Alencar Fisher Chamone; Israel Bendit Journal: Rev Bras Hematol Hemoter Date: 2013