Therapy interfering with EGFR activation in patients with cancers of oesophagus, stomach, pancreas, liver and bile ducts

Abstract

Prognosis of patients with advanced cancers of the upper digestive tract remains dismal, despite significant improvements in diagnostic and surgical techniques in recent years. In part, it may be attributed to the considerable resistance to the standard cytotoxic treatment. Thus, there is ongoing extensive search for so called “targeted therapies” that are aimed at specific molecular abnormalities in cancer cells. Epidermal growth factor receptor (EGFR) intracellular signaling transduction pathways may constitute such targets. Importantly, molecular abnormalities related to above mentioned signaling pathways are frequently encountered in upper digestive tract neoplasms. To date, based on positive phase III clinical trials results, two novel drugs were introduced to clinical practice, e.g. trastuzumab (first line treatment of advanced gastric cancer) and erlotinib (first line treatment of advanced pancreatic cancer). However, there are significant differences in biology and pathogenesis of upper digestive tract cancers that make formulation of general treatment recommendations in this patient population impossible. It seems that in the future the indications for specific targeted therapy will be based on individual patients’ profile of molecular abnormalities in cancer cells. Moreover, it will require identification of predictive and prognostic factors enabling clinicians to select a group of patients who will derive most significant benefits from specific therapies. It should be noticed that prospective assessment of various predictive and prognostic factors was incorporated in protocols of many phase III clinical trials that were completed in recent years. However, final results of majority of these analyses are not available yet. EGFR may be the target for small molecule tyrosine kinase inhibitors or monoclonal antibodies. In this paper we present a review of the results of clinical trials assessing targeted therapy interfering with EGFR in patients with upper digestive tract cancers that were reported in recent years.
Onkol. Prak. Klin. 2011; 7, 4: 183–196