The tyrosine kinase inhibitor cediranib for non-small cell lung cancer and other thoracic malignancies.
Cediranib (AZD2171; Recentin, AstraZeneca, Wilmington, Delaware) is a once-daily oral tyrosine kinase inhibitor that targets vascular endothelial growth factor receptors 1, 2, and 3, c-KIT, and platelet-derived growth factor receptors. In preclinical testing it inhibits tumor angiogenesis and inhibits tumor growth in a wide range of tumor models. Phase 1 studies show cediranib to be generally well tolerated as monotherapy at doses of 45 mg/d or less, with a pharmacokinetic profile that supports once-daily oral administration and toxic effects consistent with those seen in other agents that target the vascular endothelial growth factor pathway. Encouraging results from phase 1 studies as monotherapy or in combination with chemotherapy have prompted further investigation in several thoracic malignancies, including ongoing trials in malignant mesothelioma, small cell lung cancer, and an ongoing phase 2/3 trial in non-small cell lung cancer (NSCLC) in combination with chemotherapy. The NSCLC trials include patients with squamous cell histologic features and treated brain metastases, populations for which bevacizumab is currently not indicated. These trials will determine whether cediranib will join the growing armamentarium of therapeutic options for thoracic malignancies and broaden the number of patients with NSCLC who could potentially benefit from antiangiogenic therapy.
Nikolinakos
Petros
P
Department of Thoracic/Head and Neck Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas 77030-4009, USA. jheymach@mdanderson.org
Heymach
John V
JV
D000284:Administration, Oral; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage*; D000818:Animals; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000556:secondary; D017321:Clinical Trials, Phase I as Topic; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008297:Male; D009367:Neoplasm Staging; D011379:Prognosis; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D011799:Quinazolines / Q000008:administration & dosage* / Q000009:adverse effects; D018570:Risk Assessment; D016019:Survival Analysis; D013899:Thoracic Neoplasms / Q000188:drug therapy / Q000401:mortality / Q000473:pathology; D007211:Indoles
D020533:Angiogenesis Inhibitors; D011505:Protein-Tyrosine Kinases; D011799:Quinazolines; C500926:cediranib; D007211:Indoles