Dermatologic adverse events to targeted therapies in lower GI cancers: clinical presentation and management

Rapid advances in drug discovery and the regulatory approval of a number of novel anticancer agents during the past decade pose unique challenges to the oncology community. While the benefits of such therapies receive most attention, adverse events (AEs), especially those pertaining to subspecialties (e.g., dermatology), often are underemphasized. To ensure best clinical outcomes, it would be important to bridge the gap between approval of a new drug and devising effective management strategies for the AEs. With the incorporation of targeted therapies to the treatment paradigm of gastrointestinal malignancies, there has been a significant rise in dermatologic AEs among those treated. In addition to significantly affecting patients' quality of life, these AEs represent a growing problem and are relatively unfamiliar to many oncologists. The issue is further complicated by the lack of evidence-based management guidelines for such AEs in the oncology setting, the "generalizing" of terminology (e.g., rash) for some AEs, as well as an insufficient number of oncodermatologists for assistance with their management. It is important for the oncologist to gain familiarity with the most common, manageable and predictable AEs. Their identification is usually based on medical history, clinical features, and full-body skin examination (FBSE) and at times by obtaining a skin biopsy to aid in diagnosis. Although efforts are underway, presently, there is a paucity of biomarkers (e.g., serologic, genetic) to predict dermatologic AEs. Management often requires a multifaceted approach and includes topical, systemic, surgical, and physical (e.g., cryotherapy) modalities of treatment. Unfortunately, very few clinical trials have focused on this aspect of supportive care; therefore, most data on management derives from anecdotal data. Patients should be encouraged to actively report skin problems, while oncologists should play a vital role in addressing these AEs in their patients. Lastly, further research at the molecular and cellular level may assist in the elucidation of the mechanisms underlying these AEs and their clinical correlates, paving way for the design of effective therapies in this subset of patients.