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Various toxicities: case report A 73-year-old man developed rash, diarrhoea and paronychia following treatment with afatinib for lung adenocarcinoma. He also developed drug resistance during treatment with afatinib and icotinib for lung adenocarcinoma. The man presented with cough with phlegm and tightness in his chest. His medical history was significant for hypertension, coronary artery disease and resection of rectal carcinoma. Based on further investigations, he was diagnosed with stage IV lung adenocarcinoma. High-throughput sequencing of the initial pleural fluid specimen displayed EGFR exon 18 G724S (57.5%) and exon 20 S768I (60.5%) mutations. He was treated with three cycles carboplatin and pemetrexed leading to partial response. He experienced weak loss of appetite [aetiology not stated]. Carboplatin and pemetrexed were discontinued. Thereafter, he started receiving oral icotinib 125mg three times a day. After a month, progressive disease was noted. Therefore, his icotinib therapy was switched to oral afatinib 40mg daily. Partial response was noted after three months of afatinib therapy. However, he developed moderate diarrhoea, mild rash and mild paronychia secondary to afatinib therapy [time to reaction onsets and outcomes not stated]. The man’s afatinib dose was decreased to 30mg daily. After six months of afatinib therapy, CT scan revealed increase in size of the right lower lobe nodules indicative of progressive disease. Afatinib was discontinued. A high-throughput gene testing of peripheral blood showed EGFR exon 18 G724S (20.67%), exon 20 S768I (20.11%), and novel 790M (5.01%) mutation. Thereafter, he was initiated on osimertinib 80mg daily. However, 15 days after the treatment, he developed heavy coughing. CT scan revealed disease progression. It was concluded that, development of drug resistance to afatinib and icotinib was related to the development of T790M mutation during the treatment. Thereater, he was initiated on combined treatment with osimertinib and afatinib 30g daily. After 15 days, complete remission of cough was observed. CT scan revealed stable condition. However, a re-examination displayed progression of the disease along with development of liver metastases. He was then treated with anlotinib. Thereafter, CT scan and tumour marker evaluation revealed stable condition. Zhang C, et al. Response to tyrosine kinase inhibitors in lung adenocarcinoma with the rare epidermal growth factor receptor mutation S768I and G724S: A case report and 803508363 literature review. Thoracic Cancer 11: 2743-2748, No. 9, Sep 2020. Available from: URL: http://doi.org/10.1111/1759-7714.13606

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Reactions 17 Oct 2020 No. 1826