Head and Neck Cancer Molecular Targeted Therapy
Novel therapies for head and neck cancer include agents that target the HER family, PARP, AKT pathway, SRC-family, MET and COX pathways as well as therapies that specifically target angiogenesis.
Erbitux and vectibix are EGFR inhibitors (epidermal growth factor inhibitors) that have shown great efficacy combined with chemotherapy in the neoadjuvant as well as in metastatic disease. The major side effect of the EGFR inhibitors is a skin with a rash which also correlates with the efficacy of the drug the worse the rash the better the response. The company that manufactures this drug provides patients with soaps and lotions for prevention. At times it is necessary to prescribe antibiotics like doxycicline.
Zalutumamab is the most recent EGFR inhibitor and is a monoclonal antibody that is fully human compared to the previous two, which means that the likelihood of hypersensitivity is low. This molecule has shown good results in heavily pre-treated patients, and again the major side effect is a rash.
The VEGF-R inhibitors (vascular endothelial growth factor receptor) like bevacizumab showed that the antiangiogenic therapy combined with radiation and chemotherapy improved disease free survival and overall survival in locally advanced head and neck cancers without bleeding complications.
Vandetanib also is an antiangiogenic targeting the tyrosine kinase activity of VEGFR has shown radio sensitizing activity. Hypertension is a common side effect from antiangiogenic therapy. Bleeding is a much less common side effect, but these drugs should be avoided in patients with a history of gastrointestinal bleeding.
Ongoing trials are currently testing the efficacy of drugs that target the M-TOR pathway like temsirolimus which appear to have a synergistic effect when used in combination with radiation or chemotherapy. The drug is intravenous on a weekly basis but is extremely well tolerated.
Sorafenib and sunitinib are multikinase inhibitors that target the intracellular activity of VEGF-R. These drugs have shown very promising activity in Phase I and II trials for head and neck cancers. Currently sorafenib and sunitinib are in phase III trials, the great advantage of these drugs for patients is that they are in a pill form and are very well tolerated by people of all ages.
The therapeutic options are increasing rapidly giving more effective and less toxic options based on specific pathways over expressed by the tumors.