Association between gefitinib and hemorrhagic cystitis and severely contracted bladder: a case report
© Arakawa et al; licensee BioMed Central Ltd. 2010
Received: 25 June 2009
Accepted: 26 February 2010
Published: 26 February 2010
Gefitinib remains an excellent treatment option for patients with a variety of cancers, including non small cell lung cancer (NSCLC). However, clinicians must be aware of the potential of gefitinib to cause an inflammatory reaction in the skin, lungs and bladder.
We present a case on hemorrhagic cystitis and severaly contracted bladder in a patient with NSCLC on gefitinib.
Further studies are needed to substantiate the association of gefitinib therapy with hemorrhagic cystitis and contracted bladder.
Epidermal growth factor receptor (EGFR) plays an important role in the growth, development and progression of non small cell lung cancer (NSCLC) . Gefitinib (Iressa®) is an oral selective inhibitor of EGFR tyrosine kinase that has demonstrated efficacy in randomized double-blind phase III trials of the treatment of advanced NSCLC [2, 3]. The side effect profile of gefitinib is quite acceptable, with diarrhea and skin rash, the most commonly reported side effects [2, 3]. However, in addition to these main adverse events in Japan up to November 2008, a report by the pharmaceutical company to the Ministry of Health, Labour and Welfare indicated that 18 patients developed hematuria and 16 patients were diagnosed with hemorrhagic cystitis, which were induced by gefitinib, although the mechanism remains unclear. There is a report that severe hemorrhagic cystitis due to gefitinib was observed in only one of 25 patients . We report a rare case in which microhematuria and lower urinary tract symptoms (LUTS) led to the diagnosis of hemorrhagic cystitis and a severely contracted bladder in a patient with NSCLC treated with gefitinib. The development of a severely contracted bladder can greatly impede urine storage, which can have severe effects on quality of life, necessitating major urinary reconstructive surgery.
Known causes of hemorrhagic cystitis include severe urinary tract infection, pelvic irradiation and alkylating anticancer agents. This report describes a case of hemorrhagic cystitis and a severely contracted bladder associated with gefitinib therapy. Our patient had no risk factors for the development of hemorrhagic cystitis and contracted bladder.
It is feasible that gefitinib therapy alone induced these inflammatory changes within the bladder, or it may have exacerbated non-bacterial cystitis presenting as LUTS and microscopic hematuria in this case of hemorrhagic cystitis and severely contracted bladder.
Hemorrhagic cystitis and the development of a severely contracted bladder have been related to lack of awareness of the risk of these side effects and belated discontinuation of gefitinib.
Gefitinib remains an excellent treatment option for patients with a variety of cancers. However, clinicians must be aware of the potential of gefitinib to cause hemorrhagic cystitis and contracted bladder, and thus must monitor for LUTS and hematuria in this cohort of patients. Further studies are needed to substantiate the association of gefitinib therapy with hemorrhagic cystitis and contracted bladder.
Written consent was obtained from the patient and his family prior to publication of this case report.
- Fontanini G, Vignati S, Bigini D, Mussi A, Lucchi H, Angeletti CA, Pingitore R, Pepe S, Basolo F, Bevilacqua G: Epidermal growth factor receptor (EGFR) expression in non-small cell lung carcinomas correlates with metastatic involvement of hilar and mediastinal lymph nodes in the squamous subtype. Eur J Cancer. 1995, 31A: 178-183. 10.1016/0959-8049(93)00421-M.View ArticlePubMedGoogle Scholar
- Kim ES, Hirsh V, Mok T, Socinski MA, Gervais R, Wu YL, Li LY, Watkins CL, Sellers MV, Lowe ES, Sun Y, Liao ML, Osterlind K, Reck M, Armour AA, Shepherd FA, Lippman SM, Douillard JY: Gefitinib versus docetaxel in previously treated non-small-cell lung cancer (INTEREST): a randomised phase III trial. Lancet. 2008, 372 (9652): 1809-1818. 10.1016/S0140-6736(08)61758-4.View ArticlePubMedGoogle Scholar
- Maruyama R, Nishiwaki Y, Tamura T, Yamamoto N, Tsuboi M, Nakagawa K, Shinkai T, Negoro S, Imamura F, Eguchi K, Takeda K, Inoue A, Tomii K, Harada M, Masuda N, Jiang H, Itoh Y, Ichinose Y, Saijo N, Fukuoka M: Phase III study, V-15-32, of gefitinib versus docetaxel in previously treated Japanese patients with non-small-cell lung cancer. J Clin Oncol. 2008, 26 (26): 4244-52. 10.1200/JCO.2007.15.0185.View ArticlePubMedGoogle Scholar
- Argiris A, Mittal N: Gefitinib as first-line, compassionate use therapy in patients with advanced non-small-cell lung cancer. Lung Cancer. 2004, 43 (3): 317-322. 10.1016/j.lungcan.2003.10.010.View ArticlePubMedGoogle Scholar
- The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2490/10/6/prepub