Study of Clinical Features of Cutaneous Side Effects Associated with ZD 1839

Abstract

Background: ZD1839 (Iressa(R)Gefitinib) is an orally active, selective epidermal growth factor (EGF) receptor tyrosine kinase inhibitor that blocks signal production pathways in cell proliferation. It is currently used in the treatment of advanced stage non-small cell lung cancer. Cutaneous side effects commonly associated with ZD 1839 treatment include acneiform eruption, dry skin and hair growth abnormalities. Cutaneous eruptions result from direct interference with functions of EGF receptor signaling in the skin. Objective: The purpose of our study was to investigate the clinical features of cutaneous side effects of ZD 1839 in Korean with literature review. We also analysed the relationship between skin rash severity, onset and objective tumor response. Method: We retrospectively reviewed medical records and the histologic materials of 23 Korean patients who had been treated with ZD 1839 at Ajou University Hospital from March 2002 to September 2003 . Results: The results are summarized as follows. 1. The most common cutaneous side effect was acneiform skin rash (56%) which is a well known complication of ZD 1839.2. Acneiform eruptions were easily controlled by oral antibiotics, such as minocycline and topical retinoid ointment. 3. The second common side effect was dry scaly skin (43%).4. We also found acute paronychia, finger tip desquamation, alopecia and intertrigo. 5. The severity of the skin rash correlated well with the treatment response of ZD 1839. 6. When the skin rash appeared within 1 week after taking ZD 1839, the skin rash was severe, and the tumor responded well to the ZD 1839. Conclusion: The results of this study suggest that acneiform eruption and dry skin are the most common cutaneous side effects of ZD 1839. The association between rash severity and onset of tumor response suggests that the rash may serve as a marker of response to ZD1839 therapy andmay be used to guide treatment to obtain optimal response. However, further prospective studies on the potentially important association between rash severity or onset and outcome of treatment with ZD 1839 are needed.