M Wasif Saif1. 1. Yale University School of Medicine, New Haven, CT, USA. wasif.saif@yale.edu
Abstract
BACKGROUND: Pancreatic cancer remains a major therapeutic challenge largely characterized by chemotherapy-refractory disease and poor responses to currently available treatments. Pivotal studies of combination chemotherapeutic agents with gemcitabine showed that responses may exceed single-agent gemcitabine, but with added toxicities. The EGFR is known to be overexpressed in pancreatic cancer and data suggest that the presence of EGFR is associated with a poor prognosis. OBJECTIVE: To analyze the current data on erlotinib and compare against other agents targeting against the EGFR pathway in pancreatic cancer. METHODS: PubMed, Ovid, Cochran and the American Society of Clinical Oncology abstract database were searched using the terms 'erlotinib', 'EGFR', 'cetuximab', 'gemcitabine', 'fluorouracil', 'capecitabine' and 'pancreatic cancer' to identify relevant studies. Only studies using erlotinib in pancreatic cancer patients were reviewed and analyzed. CONCLUSIONS: The combination of gemcitabine and erlotinib is the first combination therapy to demonstrate survival benefits in pancreatic cancer in a Phase III study albeit a modest one. Increased understanding of the EGFR pathway may permit the use of other targeted agents to either augment therapeutic efficacy or circumvent resistance. It is warranted to develop strategies to truly target our therapy with the EGFR agents by identifying those patients who are most likely to derive benefit and achieve meaningful responses.
BACKGROUND:Pancreatic cancer remains a major therapeutic challenge largely characterized by chemotherapy-refractory disease and poor responses to currently available treatments. Pivotal studies of combination chemotherapeutic agents with gemcitabine showed that responses may exceed single-agent gemcitabine, but with added toxicities. The EGFR is known to be overexpressed in pancreatic cancer and data suggest that the presence of EGFR is associated with a poor prognosis. OBJECTIVE: To analyze the current data on erlotinib and compare against other agents targeting against the EGFR pathway in pancreatic cancer. METHODS: PubMed, Ovid, Cochran and the American Society of Clinical Oncology abstract database were searched using the terms 'erlotinib', 'EGFR', 'cetuximab', 'gemcitabine', 'fluorouracil', 'capecitabine' and 'pancreatic cancer' to identify relevant studies. Only studies using erlotinib in pancreatic cancerpatients were reviewed and analyzed. CONCLUSIONS: The combination of gemcitabine and erlotinib is the first combination therapy to demonstrate survival benefits in pancreatic cancer in a Phase III study albeit a modest one. Increased understanding of the EGFR pathway may permit the use of other targeted agents to either augment therapeutic efficacy or circumvent resistance. It is warranted to develop strategies to truly target our therapy with the EGFR agents by identifying those patients who are most likely to derive benefit and achieve meaningful responses.