Group Title: BMC Urology
Title: Association between gefitinib and hemorrhagic cystitis and severely contracted bladder: a case report
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Title: Association between gefitinib and hemorrhagic cystitis and severely contracted bladder: a case report
Series Title: BMC Urology
Physical Description: Archival
Language: English
Creator: Arakawa,Maki
Nakamura,Kogenta
Yamada,Yoshiaki
Rosser,Charles
Tobiume,Motoi
Saito,Hiroko
Hasegawa,Takaaki
Honda,Nobuaki
Publication Date: 2010
 Notes
Abstract: BACKGROUND: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.CASE PRESENTATION:We present a case on hemorrhagic cystitis and severaly contracted bladder in a patient with NSCLC on gefitinib.CONCLUSIONS:Further studies are needed to substantiate the association of gefitinib therapy with hemorrhagic cystitis and contracted bladder.
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General Note: M3: 10.1186/1471-2490-10-6
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Bibliographic ID: UF00099883
Volume ID: VID00001
Source Institution: University of Florida
Holding Location: University of Florida
Rights Management: Open Access: http://www.biomedcentral.com/info/about/openaccess/
Resource Identifier: issn - 1471-2490
http://www.biomedcentral.com/1471-2490/10/6

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Arakawa et al. BMC Urology 2010, 10:6
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gBMC
Urology


Association between gefitinib and hemorrhagic

cystitis and severely contracted bladder:

a case report

Maki Arakawal, Kogenta Nakamura Yoshiaki Yamada Charles J Rosser3, Motoi Tobiume Hiroko Saito',
Takaaki Hasegawa', Nobuaki Honda2


Abstract
Background: 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.
Case Presentation: We present a case on hemorrhagic cystitis and several contracted bladder in a patient with
NSCLC on gefitinib.
Conclusions: Further studies are needed to substantiate the association of gefitinib therapy with hemorrhagic
cystitis and contracted bladder.


Background
Epidermal growth factor receptor (EGFR) plays an
important role in the growth, development and pro-
gression of non small cell lung cancer (NSCLC) [1].
Gefitinib (Iressa') is an oral selective inhibitor of EGFR
tyrosine kinase that has demonstrated efficacy in ran-
domized 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 pharma-
ceutical company to the Ministry of Health, Labour
and Welfare indicated that 18 patients developed
hematuria and 16 patients were diagnosed with hemor-
rhagic 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 [4]. We report
a rare case in which microhematuria and lower urinary
tract symptoms (LUTS) led to the diagnosis of hemor-
rhagic cystitis and a severely contracted bladder in a


Correspondence' kogenaka@aichi-med-u acjp
Department of Urology, Aichi Medical University School of Medicine,
Naqakute, Aichi 480-1195, Japan


patient with NSCLC treated with gefitinib. The devel-
opment of a severely contracted bladder can greatly
impede urine storage, which can have severe effects on
quality of life, necessitating major urinary reconstruc-
tive surgery.

Case Presentation
A 56-year-old Japanese man with biopsy-proven NSCLC
was receiving active therapy with irinotecan (60 mg/m2)
and cisplatin (60 mg/m2). Previously, the patient had
had no significant genitourinary history. The combina-
tion of irinotecan and cisplatin was stopped because of
persistent neuropenic fever and severe fatigue, and oral
gefitinib (250 mg once a day) was initiated. Approxi-
mately two weeks later, severe LUTS, fever > 101.5F
and cough were noted. Urinalysis demonstrated fewer
than 5 red blood cells/high power field, no white blood
cells and no bacteria. Urine culture was negative. Spu-
tum cultures showed chlamydial pneumonia, and the
patient was started on moxifloxacin, with immediate
improvement of cough but minimal improvement of
fever, LUTS and hematuria. Over the next month, these
symptoms persisted, together with deterioration of hepa-
tic and renal function. Gefitinib therapy was halted.
Empirically, ceftazidime was initiated and fever
improved. Two weeks after stopping gefitinib, hepatic


0 2010 Arakawa et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative
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Arakawa et al. BMC Urology 2010, 10:6
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and renal function returned to normal. However, LUTS
and microscopic hematuria continued despite negative
urine cultures. The patient was referred to the Urology
Department, and thorough investigation of hematuria (i.e.,
intravenous pyelography (IVP) assessing the kidneys and
ureters and cystourethroscopy) was performed. IVP was
normal except for a contracted, thickened bladder wall
(Figure. 1). Cystourethroscopy revealed a small capacity
bladder with erythematous lesions throughout the bladder.
Because of the small capacity bladder, hydrodilation was
performed. No discrete tumors or bladder calculi were
noted. The prostatic urethra was unremarkable without
trilobar hypertrophy or a prominent median lobe. Random
bladder biopsies were obtained as well as urinary cytologi-
cal examination. Urinary cytology was negative for malig-
nancy. Histological examination of the bladder biopsies
showed areas of denuded mucosa, submucosal edema,
increased vascularity and white blood cell infiltration, indi-
cative of hemorrhagic cystitis (Figure. 2). The symptoms
improved over the ensuing four weeks.

Discussion
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


Figure 1 Intravenous pyelography showed contracted bladder.


Figure 2 Microscopic findings of bladder biopsy specimens
revealed histological changes associated with hemorrhagic
cystitis (x 10).


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.


Acknowledgements
Written consent was obtained from the patient and his family prior to
publication of this case report

Author details
'Department of Hospital Pharmacy, Aichi Medical University Hospital,
Nagakute, Aichi 480-1195, Japan Department of Urology, Aichi Medical
University School of Medicine, Nagakute, Aichi 480-1195, Japan Department
of Urology, University of Florida, Gainesville, FL, USA

Authors' contributions
MA drafted the report, and approved the final version of the manuscript YY,
MT and NH cared for the patient and approved the final version of the
manuscript HS and TH drafted the report and approved the final version of
the manuscript CR reviewed the report and approved the final version of
the manuscript KN drafted the report, cared for the patient and approved
the final version of the manuscript

Competing interests
The authors declare that they have no competing interests


Page 2 of 3







Arakawa et al. BMC Urology 2010, 10:6 Page 3 of 3
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Received: 25 June 2009
Accepted: 26 February 2010 Published: 26 February 2010

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doi:10.1186/1471-2490-10-6
Cite this article as: Arakawa et al Association between gefitinib and
hemorrhagic cystitis and severely contracted bladder: a case report.
BMC Urology 2010 10'6


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