Systemic Therapy for Colorectal Cancer - Continued (page 2 of 2)

Bevacizumab (Anti-VEGF, Avastin)
This investigational, genetically engineered, humanized
monoclonal antibody against vascular endothelial growth factor (VEGF) inhibits tumor angiogenesis. A randomized clinical trial in patients with colorectal cancer — reported at the 2003 ASCO meeting8 — demonstrated a significant improvement in tumor response rates and prolongation of survival when bevacizumab was added to the IFL regimen. Other studies combining this agent with FOLFOX are under way. The National Surgical Adjuvant Breast and Bowel Project (NSABP) plans to investigate whether the addition of bevacizumab to cytotoxic chemotherapy will increase the cure rates for patients with stage II and III colon cancer when given as postoperative adjuvant therapy. This new clinical trial is planned to begin patient accrual later this year.

Erbitux (Monoclonal antibody C-225)
This investigational, genetically engineered, humanized monoclonal antibody directed at the epidermal growth factor receptor (EGFR) has shown activity when given alone or in combination with irinotecan as second- line treatment for patients with advanced colorectal cancer.9

Summary
There have been recent advances in the systemic therapy of colorectal cancer that have significantly improved patient outcomes. Today, 40 to 50 percent of patients with metastatic colon cancer will respond to combination chemotherapy with median survival in the 20- month range. The risk of tumor relapse can also be reduced by about 40 percent with the use of postoperative chemotherapy for patients with high-risk tumors. Genetically engineered monoclonal antibodies have shown great promise, and a variety of other targeted therapies is under investigation.

References
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8. Hurwitz, H., et al: “Bevacizumab (a monoclonal antibody to vascular
endothelial growth factor) prolongs survival in first-line colorectal
cancer (CRC): Results of a phase III trial of bevacizumab in combination
with bolus IFL (irinotecan, 5-fluorouracil, leucovorin) as first-line
therapy in subjects with metastatic CRC.” Proceedings of the
American Society of Clinical Oncology, Abstract 3545, 2003.
9. Cunningham, D., et al: “Cetuximab (C225) alone or in combination
with irinotecan (CPT-11) in patients with epidermal growth factor
receptor (EGFR) positive, irinotecan-refractory metastatic colorectal
cancer (MCRC).” Proceedings of the American Society of Clinical
Oncology, Abstract 1012, 2003.