Epidermal growth factor receptor tyrosine kinase inhibitors: Present and future role in gastrointestinal cancer treatment: A review

Background. Despite advances in conventional and targeted anticancer therapy, the prognosis remains poor for many patients with solid tumors. Ongoing research into the molecular basis of malignant disease, however, has yielded many novel agents with potential activity, including the epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). Design. This review summarizes current clinical data for EGFR-TKIs as monotherapy or in combination with 5-fluorouracil/leucovorin, irinotecan, or oxaliplatin, focusing on the rapidly developing area of colorectal, gastroesophageal, and pancreatic cancers. Results. EGFR-TKIs have limited but valuable activity as monotherapy in non-small cell lung cancer patients who have received prior anticancer treatment. The potential for application as a single agent in colorectal, gastroesophageal, and pancreatic cancers has yet to be demonstrated conclusively and deserves further investigation, especially as second- or third-line therapy. In combination with oxaliplatin-based regimens and 5-fluorouracil/leucovorin-based regimens, TKIs have shown benefits, suggesting that there may be a synergistic effect with chemotherapy. However, combinations with irinotecan-based regimens have been limited by toxicities. Conclusions. EGFR-TKIs show benefits when used in combination with chemotherapy, and the favorable toxicity profiles observed suggest that these may be of value in frail or elderly patients.