Source: professional.cancerconsultants.com
Author: staff

Researchers from the National Cancer Institute and the University of Chicago have reported that the combination of Tarceva® (erlotinib) and Avastin® (bevacizumab) is well tolerated and produces sustained responses in some patients with recurrent or metastatic squamous-cell head and neck carcinoma. The details of this study appeared in the March 2009 issue of Lancet Oncology.[1]

Tarceva is an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor. EGFRs are small proteins that are found on the surface of all cells. EGFR binds exclusively to small growth factor proteins circulating in the blood. The binding action between EGFR and growth factors stimulates biological processes within the cell to promote growth of a cell in a strictly controlled manner. However, in many cancer cells, EGFR is either abundantly over-expressed or the EGFR biological processes that normally stimulate cell growth are constantly active, leading to the uncontrolled and excessive growth of the cancer cell. Tarceva is approved by the U.S. Food and Drug Administration (FDA) for the treatment of non–small cell lung cancer and has significant activity in a variety of tumors, including hepatocellular carcinoma, pancreatic cancer, colorectal cancer, and renal cell cancer.

Avastin is a humanized monoclonal antibody that is targeted against the vascular endothelial growth factor (VEGF). Avastin is approved by the FDA for the initial treatment of advanced colorectal cancer in combination with 5-fluorouracil-based therapy and has demonstrated an improvement in survival when combined with Camptosar® (irinotecan)-based chemotherapy in the treatment of this disease. Avastin was also recently approved for the treatment of breast cancer. Avastin continues to be evaluated with different chemotherapy combinations and targeted agents, and is demonstrating impressive results in various types of cancer.

Previous studies of targeted agent therapy for head and neck cancer have shown significant activity for Erbitux® (cetuximab), which is a chimeric monoclonal antibody that binds to the outer domain of EGFR. 

The current study was a multicenter Phase I/II trial involving 10 patients in the Phase I component and 48 patients in the Phase II component of the study. All had recurrent or metastatic squamous-cell carcinoma of the head and neck and all received Tarceva and Avastin. The most common side effects were rash, diarrhea, and bleeding. Seven of the 48 patients in the Phase II component of the trial had a response, and four of these were complete. Median survival was 7.1 month, and median progression-free survival was four months. Responses were related to EGRF and VEGF tumor expression. 

Comments:
This study shows that a small but significant fraction of patients with squamous-cell head and neck cancer respond to Tarceva and Avastin. It should be possible to select appropriate patients prior to treatment based on EGRF and VEGF tumor expression.

Reference:
[1] Cohen EEW, Davis DW, Karrison TG, et al. Erlotinib and bevacizumab in patients with recurrent or metastatic squamous-cell carcinoma of the head and neck: a phase I/II study. Lancet Oncology. 2009;10:247-257.