Mucosal injury from targeted anti-cancer therapy

Background: With the increased use of so-called targeted anti-cancer therapies, there has been a change in toxicities that patients are experiencing. As most targeted therapies are given in conjunction with more traditional chemotherapeutic agents, toxicities of these combination therapies are also evolving. Whilst we increasingly understand the mechanisms underlying the toxicities of chemotherapy and radiotherapy, the addition of targeted treatments requires a new understanding of both toxicity and interacting mechanisms. Aims: The aims of this review (which formed the basis of an invited plenary lecture at the 2006 Annual conference of the Multinational Association of Supportive Care in Cancer) were to define targeted anti-cancer therapy, to describe its known impact on the mucosa, either alone, or in combination with chemotherapy with or without radiotherapy, and finally to provide an outline for future directions in research into mucosal injury from targeted anti-cancer therapies. Methodology: Two separate literature reviews were conducted. The combined reviews produced 700 papers of which approximately 70 were included in the review. Results: As with mucosal injury (or mucositis) in general, the studies are hampered by a lack of mucosal injury as primary endpoint, and the variable definitions and levels of reporting. The depth to which mucosal injury was studied was also inadequate. However, it is clear that the key to understanding toxicity is to understand the mechanism of action of the drug, from which it should be possible to predict the toxicities that will occur. Conclusions: With the increasing use of targeted anti-cancer therapies, mucosal injury, particularly in its manifestations of diarrhoea, and mouth ulcers, is becoming even more prominent. More publications of basic and clinical research in this area is required.