title: The current role of high-dose imatinib in chronic myeloid leukemia patients, newly diagnosed or resistant to standard dose.
abstract: BACKGROUND
  The majority of patients affected by chronic myeloid leukemia (CML) are expected to obtain a favorable outcome with standard-dose imatinib. However, a third of patients do not achieve the desired effect and must be considered resistant. One of the early strategies to overcome initial resistance was the use of high doses (600 - 800 mg) of imatinib: before the advent of second-generation tyrosine kinase inhibitors, some standard-dose-resistant patients gained benefits from the use of dose-escalation imatinib. Intensification with higher doses of the drug was used in newly diagnosed patients with the aim to improve cytogenetic and molecular responses.
  
  
  METHODS
  In this article, the authors review data of several trials testing high-dose imatinib after resistance to standard dose. Literature about high-dose imatinib used front-line as single treatment or with different combinations is also examined. A literature search for relevant studies was undertaken mainly in PubMed or through published conference abstracts. The aim of this review is to summarize the efficacy and safety of this option either as front-line or as a rescue therapy in chronic-phase CML patients and to discuss the future role of this treatment modality.
  
  
  CONCLUSIONS
  Literature evidence supports the fact that high-dose imatinib can induce sustained responses in a subset of patients with cytogenetic failure or acquired resistance, but it seems less effective in patients with haematological failure or in molecular suboptimal responders. In newly diagnosed patients, high-dose imatinib produced increased response rates, which in some instances were not significant compared with standard dose.
authors: Sapienza University, Department of Human Biotechnologies and Hematology, Via Benevento 6, Rome, Italy. breccia@bce.uniroma1.it
authors: Massimo
authors: M
authors: Breccia
authors: Giuliana
authors: G
authors: Alimena
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001549:Benzamides; D002986:Clinical Trials as Topic; D019008:Drug Resistance, Neoplasm; D006801:Humans; D000068877:Imatinib Mesylate; D015466:Leukemia, Myeloid, Chronic-Phase / Q000188:drug therapy*; D010879:Piperazines / Q000008:administration & dosage* / Q000009:adverse effects; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D011743:Pyrimidines / Q000008:administration & dosage* / Q000009:adverse effects; D016032:Randomized Controlled Trials as Topic; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D000068877:Imatinib Mesylate