Lung cancer is still the most deadly cancer. Dr. Susanna V. Ulahannan and Dr. Julie R. Brahmer of Johns Hopkins University Hospital in Baltimore, Md., provided a review of new treatment options based on combinations of standard chemotherapy agents with newer antiangiogenic drugs. Ulahannan and Brahmer noted that lung cancer kills more Americans than breast, colorectal, and prostate cancers combined.
Approximately 85 percent of lung cancers are categorized as non-small cell lung cancer (NSMLC), and most patients already have advanced disease at the time of diagnosis. Standard care is a combination of two platinum-based cytotoxic agents. Adding a third agent does not provide additional benefits. A large study compared four options for the doublet of chemotherapy agents, and found the same efficacy for each doublet. The combination of carboplatin and paclitaxel produced fewer episodes of toxicity.
Most chemotherapy agents attack rapidly dividing cells in general. Antiangiogenic drugs target the growth of blood vessels into tumors. Cancers are not able to grow bigger than microscopic size without new blood vessels to nourish them. Vascular endothelial growth factor, VEGF, is a key molecule in this process.
Bevacizumab (brand name Avastin) is a monoclonal antibody that inhibits VEGF from binding to its receptors, thus interfering with the growth of new blood vessels. It was approved for use in treating non-small cell lung cancer, in combination with platinum-based chemotherapy, in 2006. Bevacizumab was also marketed for colorectal cancer, glioblastoma (brain cancer), and kidney cancer. Clinical trials cited by Ulahannan and Brahmer showed positive results overall, but only about 50 percent of patients are candidates for this treatment.
Another approach to stopping blood vessel growth is to block the VEGF receptors with small molecules called tyrosine kinase inhibitors. Several drugs in this class have been tested on non-small cell lung cancer:
1. Sorafenib (brand name Nexavar) is approved and marketed for kidney cancer and liver cancer.
2. Sunitinib (brand name Sutent) is approved and marketed for kidney cancer, gastrointestinal stromal tumors, and pancreatic neuroendocrine tumors.
3. Pazopanib (brand name Votrient) is approved for kidney cancer.
4. Vandetanib is approved for a rare type of thyroid cancer.
5. Cediranib is in development.
6. Axitinib is in development.
7. BIBF 1120 is in development.
“The availability of treatment options for patients with advanced NSCLC has expanded,” Ulahannan and Brahmer reported. However, more work is needed to see which drugs are most appropriate for each patient. “The identification of effective biomarkers will be critical,” they concluded.
Currently (June 2011) there are 3590 clinical trials for lung cancer listed at http://clinicaltrials.gov/ct2/results?term=lung+cancer.
1. Ulahannan SV et al, “Antiangiogenic agents in combination with chemotherapy in patients with advanced non-small cell lung cancer”, Cancer Investigation 2011; 29: 325-37. http://www.ncbi.nlm.nih.gov/pubmed/21469981
2. Bevacizumab (Avastin): http://www.avastin.com/avastin/patient/
3. Sorafenib (Nexavar): http://www.nexavar-us.com/scripts/pages/en/index.php?WT.mc_id=NES100022&WT.srch=1
4. Pazopanib (Votrient): http://www.cancer.gov/cancertopics/druginfo/fda-pazopanibhydrochloride
5. Vandetanib: http://www.medicinenet.com/script/main/art.asp?articlekey=142832
6. Cediranib: http://www.medscape.com/viewarticle/733403
7. Axitinib: http://www.ackc.org/kidney-cancer-information/pfizer-and-axitinib-ag-013736/
8. BIBF 1120: http://www.ncbi.nlm.nih.gov/pubmed/20465363
Reviewed June 27, 2011
Edited by Alison Stanton
Linda Fugate is a scientist and writer in Austin, Texas. She has a Ph.D. in Physics and an M.S. in Macromolecular Science and Engineering. Her background includes academic and industrial research in materials science. She currently writes song lyrics and health articles.