Massive Hematuria from the Bilateral Upper Urinary Tract in a Patient Treated for Advanced Lung Cancer with Gefitinib

Abstract

We report a case of gefitinib-induced bilateral upper urinary tract bleeding in an 82-year-old woman administered the drug daily for advanced non-small cell adenocarcinoma of the lung (T4N3M0). Hematuria is an uncommon adverse effect of gefitinib, and in most cases, the bleeding site is unknown. On the 44th day of oral gefitinib administration, the patient noted asymptomatic macroscopic bloody urine. Cystoscopy revealed bleeding from the bilateral ureteric orifices without hemorrhagic inflammation of the bladder. One week later, she was admitted complaining of severe abdominal pain, and her condition was found to be complicated by liver damage and renal dysfunction. We stopped gefitinib administration and started hydration and diuresis. Renal function and urine output soon recovered, and at the request of the patient, we restarted gefitinib, administering it every other day, which was sufficient to maintain antitumor activity and stabilize the disease. On the 41st day after restarting gefitinib, hematuria and proteinuria reappeared. We therefore stopped the gefitinib, and the patient was followed with supportive care. The patient's autopsy findings denied organic urologic diseases. Instead, the reproducibility of the hematuria from the upper urinary system strongly suggests an unexpected gefitinib-related adverse effect.

Gefitinib in Non-Small Cell Lung Carcinoma: A Case Report of an Unusual Side Effect and Complete Response in Advanced Disease

“…In our patient immediate discontinuation of gefitinib and treatment of the hemorrhagic cystitis by fluid and urine alkalizing agents prevented the occurrence of more severe kidney damage and led to the disappearance of the adverse effects, while the patient still showed a remarkable response to therapy 11 .…”

A case of gefitinib-associated membranous nephropathy in treatment for pulmonary adenocarcinoma

“…Renal dysfunction was occurred in about 1 %. Other side effects were post-renal acute renal failure due to urinary bleeding or retroperitoneal fibrosis [19]. A case of acute renal failure due to thrombotic thrombocytopenic purpura/hemolytic uremic syndrome was also reported [20].…”

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

“…Pharmacokinetic studies of gefitinib have demonstrated a urinary recovery of only <0.5%, indicating that the urinary system is only a minor route of excretion (4). Despite being generally well-tolerated, a small subset of patients have reported uncommon gefitinib-induced adverse reactions affecting the urinary system, including acute renal failure (10), hematuria (12), hemorrhagic cystitis (11,13), and inflammatory contracted bladder (11). In vitro studies have demonstrated that EGFR signaling is involved in the proliferation of urothelial cells, and gefitinib can inhibit the growth of normal urothelial cells and urothelial carcinoma cell lines (16).…”

“…At the standard recommended dose, gefitinib has a tolerable safety profile (4)(5)(6), with reported adverse reactions primarily involving the gastrointestinal system (i.e., diarrhea, nausea, vomiting), skin (i.e., rash, acne, dry skin), and liver [i.e., elevated alanine aminotransferase (ALT) and aspartate transaminase (AST)] (2,5,7). However, uncommon adverse reactions have been reported, including hematuria and hemorrhagic cystitis (8)(9)(10)(11)(12)(13)(14). Clinicians should pay more attention on monitoring for urinary symptoms and hematuria.…”