Gefitinib

Abstract

Various toxicities: case report A 69-year-old man developed skin rash and multiple ulcers of the oral cavity, oesophagus, stomach and mucous membrane of the ureter, accompanied by bleeding in the form of haematemesis and haematuria during treatment with gefitinib for stage-IV lung adenocarcinoma. The man presented to hospital in January 2019 with haemoptysis and dry cough. Subsequent analyses revealed a stage-IV lung adenocarcinoma. Therefore, in February 2019, he started receiving oral gefitinib [Qilu Pharmaceutical Co., Ltd.] 250mg once daily. However, 5 months following gefitinib initiation, he was hospitalised due to haematuria and abdominal discomfort. Following admission, urinalysis revealed RBC count of 8 594.7/μL. An ultrasonogram revealed presence of kidney stone; ureteroscopy showed that the left upper ureter was surrounded by mucous membrane ulcer next to the mouth of the renal pelvis, accompanied by haemorrhage, and a stone located in the lower calyces of his right kidney. Therefore, the man underwent holmium laser lithotripsy with insertion of bilateral ureteral stents. Post-operative inspection did not reveal any tumour cells of the ureteral ulcer. Later, 3 weeks post-operatively, the ureteral stents were removed; however, the haematuria persisted. Repeat urinalysis revealed that his RBC count was over 100/μL. Further, his haemoglobin levels decreased due to bleeding from multiple ulcers. After excluding all other possibilities, the ulcers were attributed to gefitinib. However, gefitinib was continued. Forty days later, he was readmitted due to skin rash, haematemesis and acid reflux. Emergency gastroscopy confirmed the presence of multiple ulcers of the oesophagus, oral cavity and stomach along with bleeding. Urinalysis was repeated, which revealed RBC count 42 172.5/μL. Considering all these side effects of gefitinib, the treatment was discontinued, and the man started fasting, with stomach protection, appropriate skin treatment and haemostasis. He made a gradual recovery. Two weeks later, laboratory analyses revealed improvement in haematuria and haematemesis. Therefore, the man resumed oral gefitinib at a reduced dose of 125mg once daily. His digestive and urinary symptoms reappeared, though with reduced severity. He was subsequently found to have cerebral metastasis; hence, gefitinib therapy was discontinued and replaced with osimertinib [times to reaction onsets and final outcomes not stated].