Nilotinib as frontline and second-line therapy in chronic myeloid leukemia: open questions.

Abstract

Nilotinib is a second generation ABL tyrosine kinase inhibitor (TKI) that exerts major anti-leukemic effects in newly diagnosed patients with chronic myeloid leukemia (CML) as well as in most patients with imatinib-resistant CML. In freshly diagnosed patients, the anti-leukemic activity of nilotinib exceeds the efficacy of imatinib, and although long-term data for nilotinib are not available yet, the drug has recently been approved for firstline treatment of chronic phase CML in various countries. Still however, several questions concerning the optimal dose, follow-up parameters, long-term safety, and patient selection remain open. Likewise, it remains uncertain whether both Sokal low-risk and high-risk patients should receive nilotinib as frontline therapy in the future. Another question is whether nilotinib can completely eradicate CML in a subset of patients. Furthermore, it remains unclear whether and what comorbidity must be regarded as relative or absolute contra-indication for this TKI. To discuss these issues, the Austrian CML Working Group organized a series of meetings in 2010. In the current article, the outcomes from these discussions are summarized and presented together with recommendations for frontline use of TKIs in various groups of patients with CML. These recommendations should assist in daily practice as well as in the preparation and conduct of clinical trials.

• Authors: Peter Valent, Günther Gastl, Klaus Geissler, Richard Greil, Oliver Hantschel, Alois Lang, Werner Linkesch, Thomas Lion, Andreas L Petzer, Elisabeth Pittermann, Lisa Pleyer, Josef Thaler, Dominik Wolf
• Journal: Critical reviews in oncology/hematology (Crit Rev Oncol Hematol) Vol. 82 Issue 3 Pg. 370-7 (Jun 2012) ISSN: 1879-0461 [Electronic] Netherlands
• PMID: 21903413 (Publication Type: Journal Article, Review)
• Copyright: Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Chemical References

• Antineoplastic Agents
• Benzamides
• Piperazines
• Protein Kinase Inhibitors
• Pyrimidines
• Imatinib Mesylate
• Protein-Tyrosine Kinases
• Fusion Proteins, bcr-abl
• nilotinib

Topics

• Antineoplastic Agents (administration & dosage, therapeutic use)
• Benzamides
• Cerebrovascular Disorders (drug therapy, epidemiology, pathology)
• Clinical Trials as Topic
• Comorbidity
• Contraindications
• Diabetes Mellitus (drug therapy, epidemiology, pathology)
• Drug Administration Schedule
• Fusion Proteins, bcr-abl (antagonists & inhibitors, metabolism)
• Humans
• Imatinib Mesylate
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive (drug therapy, epidemiology, pathology)
• Patient Selection
• Piperazines (administration & dosage, therapeutic use)
• Practice Guidelines as Topic
• Protein Kinase Inhibitors (administration & dosage, therapeutic use)
• Protein-Tyrosine Kinases (antagonists & inhibitors, metabolism)
• Pyrimidines (administration & dosage, therapeutic use)
• Treatment Outcome