Appearance of 4 Degree Rash While Treating Advanced Lung Cancer with Icotinib – Whether to Stop the Drug: A Case Report

Skin and skin adnexa toxicities are the most common side effects associated with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). Previous research showed that the rash appeared, and the severity of EGFR-TKIs may be a marker of clinical benefit. In this context, we report a 75-year-old man with advanced lung cancer who on receiving icotinib developed severe adverse reactions, 4 degree rash (NCI-CTC AE version 4.0 common toxicity grading standards grade), and refused to stop taking the drug; but with the anti-infection and symptomatic nursing, the patient recovered, the rash disappeared, and the patient received a better prognosis. Thus, we would like to emphasize the importance of deciding whether to stop the drug when patients developed adverse reactions of 3-4 degree rash. © 2020 Jie Lin. Hosting by Science Repository. All rights reserved.


Introduction
Icotinib is a first-generation EGFR-TKI developed by Zhejiang Beta Pharma in China, which is the first small molecular targeted drugs and has gained international recognition [1]. The main adverse reactions of icotinib are rash and diarrhea; the incidence of adverse events and the severity of rash were lower than gefitinib and erlotinib [2][3][4][5]. In terms of efficacy, icotinib and gefitinib are equivalent, but icotinib has a better security [6]. Therefore, for patients with EGFR mutation and the elderly who cannot tolerate chemotherapy, icotinib is more appropriate [3]. We report a 75-year-old man with advanced lung cancer who received icotinib, developed severe adverse reactions, and refused to stop taking the drug, but through anti-infection the rash disappeared and the patient received a better prognosis.

Case Report
The patient, a 75-year-old male with "recurrent cough, sputum for more than 30 years, and then increased with left chest pain more than 4 months" was admitted. The chest computed tomography (CT) scan showed: left lower lobe mass shadow, more likely to consider the surrounding lung cancer, bilateral middle volume of pleural effusion; bone scan showed multiple metastatic bone lesions. He underwent a bilateral pleural effusion puncture drainage operation, and the cytology test showed malignant tumor cells. We could not further clarify the pathological type of lung cancer because the patient refused further pathological examination. Through the combination of tumor markers detection and clinical manifestations, he was considered to be diagnosed with lung adenocarcinoma and clinically staged as cT2aN0M1b, stage IV. So, this patient was given "bevacizumab 100mg and cisplatin 30mg and normal saline 20ml" pleural perfusion chemotherapy 2 times. Blood tests found mutations in EGFR; so, the patient received 125 mg oral icotinib in tablet form three times per day to maintain. This study was conducted in accordance with the declaration of Helsinki. This study was conducted with approval from the Ethics Committee of The Second Affiliated Hospital of Kunming Medical University. Written informed consent was obtained from all participants.
But the patient's face began to develop red papules after taking icotinib for 7 days, which were considered the side effects of drugs, but he did not receive any special treatment. Since then, the rash was significantly increased, fused into masses, canker scab, accompanied by purulent secretions (Figures 1A1 & 1A2). We recommended that patient stops taking icotinib, but he refused, worrying about rapid recurrence and metastasis. The abscess on the face of the patient was cut open and drained in surgery. The biopsy of the bump showed squamous epithelium hyperplasia, with atypical hyperplasia, chronic inflammation of the dermis and abscess formation ( Figures 1B1 & 1B2). After 2 weeks of anti-infection treatment, the patient's skin rash wound secretion decreased, and the granulation rate was slow ( Figures 1C1 & 1C2). Twenty days later, CT revealed tumor regression; the curative effect was evaluated as partial remission (PR) (Figures 2A & 2B). Two months later ( Figures 2C1 & 2C2), and three months later ( Figures 2D1 & 2D2), a PR was also confirmed in the chest CT scan. However, four months later, the CT scan revealed that the tumor grew larger, the efficacy was evaluated as progressive disease (PD) (Figures 2E1 & 2E2). After medication for more than 7 months, a PD was confirmed in the chest CT scan ( Figures 2F1 & 2F2). In addition, the tumor markers of patient were significantly decreased (Table 1).

Discussion
EGFR-TKIs inhibitor development has shown great superiority in the treatment of lung cancer, but it also brings a variety of skin toxicity [7]. Previous studies confirm that the presence and severity of rash may be a sign of clinical benefit for EGFR-TKIs, which can predict the risk of disease progression [8][9][10]. Thus, icotinib for the treatment of advanced non-small cell lung cancer and skin rash may be a good prognostic factor.
We report that this patient's face developed 4 degree rash after taking icotinib. According to evidence of withdrawal of adverse reactions to icotinib, it is generally recommended that patients stop taking the drug, but this patient refused to stop taking icotinib; but with active symptomatic treatments, the left temporal mass disappeared [11]. The PFS of this patient was 4.7 months and the OS was 8.0 months, which was similar to the results of ICOGEN studies [6]. And this patient's tumor markers CEA, CA125 decreased significantly, and the tumor was also significantly reduced.
In conclusion, icotinib for the treatment of advanced non-small cell lung cancer can be used as a choice, and the rash may be a good prognostic sign. Clinical workers need to further explore whether targeted therapy should be discontinued when severe adverse skin reactions occur. A large number of clinical trials are needed for that.