Vascular endothelial growth factor receptor tyrosine kinase inhibitors in non-small cell lung cancer: a review of recent clinical trials.
Non-small cell lung cancer (NSCLC) remains the leading cause of cancer-related mortality in the United States. Therapeutic agents that target the underlying biology of this disease are necessary to improve outcomes. Angiogenesis plays a central role in NSCLC tumor growth and metastases. The vascular endothelial growth factor pathway (VEGF) as a therapeutic target was recently validated in NSCLC. Since then, a multitude of early phase clinical trials that incorporate the use of angiogenesis inhibitors, either as single agents or in combination with cytotoxic chemotherapy, have been conducted in advanced, refractory NSCLC. This article reviews these clinical trials with attention to toxicity, efficacy, and direction of further study. The data from these trials suggest that optimal use of anti-angiogenic agents in NSCLC is more likely in combination with standard cytotoxic agents, however the most effective combination with the least toxicity is yet to be determined.
Lee
Carrie B
CB
Multidisciplinary Thoracic Oncology Program, Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599-7305, USA.
Socinski
Mark A
MA
D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001557:Benzenesulfonates / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D002986:Clinical Trials as Topic; D006801:Humans; D007211:Indoles / Q000627:therapeutic use; D009389:Neovascularization, Pathologic / Q000188:drug therapy*; D009536:Niacinamide / Q000031:analogs & derivatives / Q000627:therapeutic use; D009841:Oligonucleotides; D010671:Phenylurea Compounds; D010793:Phthalazines / Q000627:therapeutic use; D010880:Piperidines / Q000627:therapeutic use; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D011725:Pyridines / Q000627:therapeutic use; D011758:Pyrroles; D011799:Quinazolines / Q000627:therapeutic use; D040262:Receptors, Vascular Endothelial Growth Factor / Q000187:drug effects; D000077157:Sorafenib; D000077210:Sunitinib; D016896:Treatment Outcome
D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D001557:Benzenesulfonates; D007211:Indoles; D009841:Oligonucleotides; D010671:Phenylurea Compounds; D010793:Phthalazines; D010880:Piperidines; D011725:Pyridines; D011758:Pyrroles; D011799:Quinazolines; D009536:Niacinamide; C404768:vatalanib; D000077157:Sorafenib; D011505:Protein-Tyrosine Kinases; D040262:Receptors, Vascular Endothelial Growth Factor; C519562:imetelstat; C500926:cediranib; D000077210:Sunitinib; C452423:vandetanib