Gefitinib-induced hemorrhagic cystitis and inflammatory contracted bladder in a patient with advanced lung adenocarcinoma harboring compound epidermal growth factor receptor G719S and S768I missense mutations: a case report

Background: Numerous clinical studies have established the efficacy and safety of gefitinib for treating patients with epidermal growth factor receptor (EGFR)-mutant lung cancer. Gefitinib-induced urinary system-related adverse reactions are rare but may lead to discontinuation of gefitinib. Case Description: In our report, we describe a patient with advanced lung adenocarcinoma harboring compound EGFR G719S and S768I who developed hemorrhagic cystitis and inflammatory contracted bladder during first-line gefitinib therapy. A 56-year-old male smoker, presented with chronic cough, sputum expectoration, and shortness of breath for 6 months that had worsened over the last 2 weeks, was diagnosed with T2N2MIA stage IV adenocarcinoma of the right lower lung with bilateral lung metastases. Upon detecting a compound EGFR G719S and S768I using a next-generation sequencing-based assay, the patient was administered with gefitinib (250 mg/day) as a first-line regimen. Despite achieving partial response (PR) within 6 weeks of gefitinib therapy, the patient developed several drug-related adverse reactions, including diarrhea, elevated liver enzymes, and inflammatory contracted bladder with hemorrhagic cystitis. Routine urinalysis indicated full high-power field (HPF) view of red blood cell (RBC) and 40-50 white blood cell (WBC) counts/HPF at 1.5 months of gefitinib therapy as compared with no RBC and WBC per HPF before gefitinib therapy (normal range: 0-1 RBC/HPF and 0-3 WBC/HPF). The urinary symptoms and hematuria were alleviated after discontinuation of gefitinib. Icotinib was administered without benefit and subsequently switched to afatinib as the third-line therapy. A PR was achieved; however, it only lasted for 3 months. Then the patient was lost to follow-up. Conclusions: Our case shows that gefitinib can induce hemorrhagic cystitis and contracted bladder. Clinicians must be aware that these uncommon adverse reactions affecting the urinary system could occur in patients with EGFR-mutant lung adenocarcinoma. Monitor for urinary symptoms and hematuria in this cohort of patients is essential.