Cutaneous adverse events of epidermal growth factor receptor inhibitors: A retrospective review of 99 cases.

Background: Previous reports regarding the cutaneous adverse events of epidermal growth factor receptor inhibitors are mostly limited to small case reports and case series, mainly involving Caucasian patients. Aims: We describe the trends in the clinical presentation of Asian patients who had cutaneous adverse events induced by epidermal growth factor receptor inhibitors and to explore the relationship between skin adverse events and tumor response. Methods: From 2006 to 2010, medical records of Thai patients with non‑small cell lung cancer receiving epidermal growth factor receptor inhibitors were retrieved and analyzed. Results: In all, 99 patients were reviewed and analyzed. Erlotinib and gefitinib were commenced in 75 (75.8%) and 24 (24.2%) patients, respectively. Cutaneous adverse events occurred in 43 (57.3%) patients receiving erlotinib and in 15 (62.5%) patients receiving gefitinib. The most common adverse event was xerosis (52.5%). Less common adverse events included papulo-pustular eruption (27.3%), erythematous maculopapular rash (11.1%), mucositis (6.7%), paronychia (5.1%), and trichomegaly (2%). Elderly patients had a higher occurrence of xerosis. The presence of cutaneous adverse events was significantly higher in subjects who had a tumor response. Limitations: The limitations of study include its retrospective nature, and the initial screening of cutaneous adverse events was done by non‑dermatologists. Conclusions: Cutaneous adverse events due to epidermal growth factor receptor inhibitors are not uncommon in the Asian population. We found a positive correlation between the occurrences of cutaneou adverse events and tumor response supporting the view that they are surrogate markers for therapeutic response.

Cutaneous Adverse Reactions Associated with Epidermal Growth Factor Receptor Inhibitors / 대한피부과학회지

BACKGROUND: Cutaneous adverse reactions are often observed during chemotherapy with epidermal growth factor receptor (EGFR) inhibitors including papulopustular eruptions, xerosis and paronychia. OBJECTIVE: To investigate and compare the cutaneous adverse reactions induced by EGFR inhibitors including erlotinib, gefitinib and cetuximab which have commonly been used as chemotherapeutic agents in Korea. METHODS: We reviewed cutaneous adverse effects through the medical records and clinical photographs of 43 Korean patients who had been treated with erlotinib, gefitinib or cetuximab at Pusan Paik Hospital between June 2003 and January 2010. RESULTS: Papulopustular eruptions occurred in 28 patients (65.1%); they were easily controlled by topical benzoyl peroxide, clindamycin and a retinoid, or by oral minocycline and tetracycline. There were no significant differences in incidence, duration and severity grades of papulopustular eruptions among EGFR inhibitors. In contrast to previous studies, the frequency and severity of papulopustular eruptions were not significantly correlated with treatment responses to EGFR inhibitors. Xerosis appeared in 14 patients (41%), and was easily controlled by topical emollients and steroids, and by systemic steroids and antihistamines. Paronychia occurred in 8 patients (18.6%) and were controlled by conservative treatments. CONCLUSION: Papulopustular eruptions, xerosis and paronychia are common cutaneous adverse reactions associated with EGFR inhibitors and there are no significant differences in adverse cutaneous reactions among EGFR inhibitors. As these cutaneous adverse reactions are relatively easily controlled with treatment, it will be helpful to detect and treat these adverse reactions early, including reassuring the patients, which should increase compliance of patients during treatment with EGFR inhibitors.

Clinical Features of the Cutaneous Adverse Events Induced by Combination Chemotherapy that Includes Cetuximab (Erbitux(R)) / 대한피부과학회지

BACKGROUND: Epidermal growth factor receptor (EGFR) inhibitors are associated with cutaneous adverse events, including papulopustular eruption, xerosis, paronychia, hair abnormality and mucositis. In particular, acneiform eruptions might serve as the visible markers of anti-tumor activity and the therapeutic efficacy of EGFR inhibitors. OBJECTIVE: Our aims are to investigate the common cutaneous adverse events induced by cetuximab, which is one of the EGFR inhibitors approved by the US Food and Drug Administration, and to analyze whether the presence and severity of papulopustular eruptions have a correlation with the tumor response. METHODS: We retrospectively reviewed the medical records and clinical photographs of 114 Korean patients who had been treated with cetuximab at Asan Medical Center from September 2004 to March 2007. Results: Papulopustular eruptions occurred in 100 patients (87.7%) and this usually happened 10 days after starting chemotherapy. There was a tendency that the better the tumor responded to the chemotherapeutic agents including cetuximab, the more severe were the papulopustular eruptions. The papulopustular eruptions prominently improved after the treatment with topical agents such as benzoyl peroxide, metronidazole, clindamycin and retinoid, and with systemic agents such as minocycline and tetracycline, and there was no adverse event induced by this treatment for papulopustular eruptions. Xerosis appeared in 67 patients (58.8%), and there was a tendency that the more severe papulopustular eruptions were, the more frequently xerosis occurred. Paronychia occurred in 8 patients (7.0%). CONCLUSION: Although the cutaneous adverse events are burdensome to the patients, they might serve as visible markers of the anti-tumor activity and therapeutic efficacy of cetuximab and they can be easily and safely controlled with many topical and systemic agents. Therefore, it is important for dermatologists to properly treat these cutaneous adverse events and to reassure the patient to continue with the cetuximab treatment.