Angiogenesis inhibition in the treatment of lung cancer.
Antiangiogenic therapy has emerged as an important concept in the treatment of solid tumors, including non-small cell lung cancer (NSCLC). Vascular endothelial growth factor (VEGF) represents an important therapeutic target, as it is the primary mediator of angiogenesis and is induced by multiple tumor-relevant stimuli. The anti-VEGF monoclonal antibody bevacizumab has demonstrated a significant clinical benefit in patients with non-squamous cell NSCLC in a randomized phase III trial. The addition of bevacizumab to chemotherapy with paclitaxel plus carboplatin provided a significant survival benefit over chemotherapy alone. Bevacizumab is associated with an increased risk of severe bleeding; thus, patients should be carefully selected for bevacizumab treatment. Hypertension is also seen with bevacizumab but can be managed with antihypertensive agents. Ongoing studies are evaluating bevacizumab in other NSCLC settings and are attempting to identify predictive factors for responses to bevacizumab. Antiangiogenic approaches other than bevacizumab are also being investigated, including several small-molecule tyrosine kinase inhibitors that have demonstrated activity in small studies. In some cases, combination therapy with different targeted agents may provide the most comprehensive treatment approach. In a randomized phase II study, bevacizumab in combination with the epidermal growth factor receptor inhibitor erlotinib demonstrated efficacy similar to chemotherapy plus bevacizumab. Ongoing studies are continuing to investigate new agents and identify the patients most likely to benefit from antiangiogenic therapy.
Vokes
Everett
E
University of Chicago, Chicago, IL, USA.
Herbst
Roy
R
Sandler
Alan
A
D020533:Angiogenesis Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D000068258:Bevacizumab; D016190:Carboplatin / Q000008:administration & dosage / Q000009:adverse effects; D002289:Carcinoma, Non-Small-Cell Lung / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D017326:Clinical Trials, Phase III as Topic; D018572:Disease-Free Survival; D000069347:Erlotinib Hydrochloride; D006470:Hemorrhage / Q000139:chemically induced / Q000401:mortality; D006801:Humans; D008175:Lung Neoplasms / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D009389:Neovascularization, Pathologic / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D011799:Quinazolines / Q000009:adverse effects / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D012307:Risk Factors; D015996:Survival Rate; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors
D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab; D016190:Carboplatin; D000069347:Erlotinib Hydrochloride; D017239:Paclitaxel