Chemotherapy side effects and EGFRIs

ADVERSE EFFECTS OF CANCER THERAPY: PREVENTION IS BETTER THAN CURE.
V. A. Preda1, J. R. Sullivan1
1Dermatology, Liverpool Hospital, University of New South Wales, Sydney, Australia
Biological treatments, such as the epidermal growth factor receptor (EGFR) inhibitors, are increasingly being used in a range of tumor types including head and neck, colon, breast, ovarian and brain. At least for cetuximab, a monoclonal EGFR inhibitor, it has been shown to have synergistic benefits when used in conjunction with radiotherapy.
In contrast to the traditional chemotherapy agents with systemic side effects, these agents have an evolving profile of adverse mucocutaneous reactions. The most common side effect of the EGFR inhibitors is an acne-like eruption, which in the setting of combination radiotherapy can be superimposed on radiation dermatitis. Changes occurring later on include paronychia, dry atrophic cracked, fissured, fragile, telangectatic skin, nail and hair changes, staphylococcal colonization which can have superimposed infection. These changes show similarities to the cutaneous toxicities seen in retinoid therapy, immunosuppression and immune reconstitution, a number of inflammatory/infective dermatoses and irritant skin reactions. The potentially treatment-limiting impact of these cutaneous toxicities associated with EGFR inhibitors warrants review of the side effect management, rather than purely reactionary post-chemoradiotherapy management.
The majority of the literature pertaining to the management of these side effects refers to the European population. By virtue of our geography and ethnic background, the Australian SCCHN population is a unique group for EGFR inhibitor therapy, differing considerably from the European population. The interplay between traditional oncology therapies, the EGFR inhibitor along with geographical considerations (hot humid versus cold dry climate, high verus low ultraviolet exposure), patient factors (dysplastic and inflammatory skin disease, ethnicity) and cancer related factors is likely to explain the great variation in reaction severity seen between patients and requires further study.
Pre-emptive measures, in conjunction with ongoing good skin care regimes may decrease severity of both the mucocutaneous side effects of the EGFR inhibitors and radiotherapy. Guidelines should be based on global experience and drug safety lessons learnt from cutaneous drug reactions with similar features and time frames. Review is also warranted for greater understanding of the diverse skin substrates in patients receiving radiotherapy and EGFR inhibitors, as this becomes the mainstay of therapy in the future.

References: 1. Bonner JA, Harari PM, Giralt T et al. Radiotherapy plus cetuximab for squamous cell carcinoma of the head and neck. N Engl J Med 2006;354:567-78
2. Lacouture ME. Mechanisms of cutaneous toxicities to EGFR inhibitors. Nat Rev Cancer 2006;6:803-11.
3. Budach W, Bölke E, Homey B. Severe cutaneous reaction during radiation therapy with concurrent cutuximab. N Engl J Med 2007; 357: 514-515