Incidence of Cyclophosphamide-induced Urotoxicity and Protective Effect of Mesna in Rheumatic Diseases

Neslihan Yilmaz; Hakan Emmungil; Sercan Gucenmez; Gulsen Ozen; Fatih Yildiz; Ayşe Balkarli; Gezmis Kimyon; Belkis Nihan Coskun; Ismail Dogan; Omer Nuri Pamuk; Sule Yasar; Gozde Yildirim Cetin; Ayten Yazici; Serpil Ergulu Esmen; Yonca Cagatay; Sema Yilmaz; Ayse Cefle; Mehmet Sayarlioglu; Timucin Kasifoglu; Omer Karadag; Yavuz Pehlivan; Ediz Dalkilic; Bunyamin Kisacik; Veli Cobankara; Eren Erken; Haner Direskeneli; Kenan Aksu; Sule Yavuz

doi:10.3899/jrheum.150065

Incidence of Cyclophosphamide-induced Urotoxicity and Protective Effect of Mesna in Rheumatic Diseases

J Rheumatol. 2015 Sep;42(9):1661-6. doi: 10.3899/jrheum.150065. Epub 2015 Jul 15.

Authors

Neslihan Yilmaz¹, Hakan Emmungil¹, Sercan Gucenmez¹, Gulsen Ozen¹, Fatih Yildiz¹, Ayşe Balkarli¹, Gezmis Kimyon¹, Belkis Nihan Coskun¹, Ismail Dogan¹, Omer Nuri Pamuk¹, Sule Yasar¹, Gozde Yildirim Cetin¹, Ayten Yazici¹, Serpil Ergulu Esmen¹, Yonca Cagatay¹, Sema Yilmaz¹, Ayse Cefle¹, Mehmet Sayarlioglu¹, Timucin Kasifoglu¹, Omer Karadag¹, Yavuz Pehlivan¹, Ediz Dalkilic¹, Bunyamin Kisacik¹, Veli Cobankara¹, Eren Erken¹, Haner Direskeneli¹, Kenan Aksu¹, Sule Yavuz¹

Affiliation

¹ From the Rheumatology Department, Faculty of Medicine, Istanbul Bilim University; Rheumatology Department, Faculty of Medicine, Marmara University, Istanbul; Rheumatology Department, Faculty of Medicine, Ege University, İzmir; Rheumatology Department, Faculty of Medicine, Cukurova University, Adana; Rheumatology Department, Faculty of Medicine, Pamukkale University, Denizli; Faculty of Medicine, Gaziantep Rheumatology University, Gaziantep; Rheumatology Department, Faculty of Medicine, Uludag University, Bursa; Rheumatology Department, Faculty of Medicine, Hacettepe University, Ankara; Rheumatology Department, Faculty of Medicine, Trakya University, Edime; Rheumatology Department, Faculty of Medicine, Eskişehir Osmangazi University, Eskişehir; Rheumatology Department, Faculty of Medicine, Kahramanmaraş Sütçüimam University, Kahramanmaraş; Rheumatology Department, Faculty of Medicine, Kocaeli University, İzmit; Rheumatology Department, Faculty of Medicine, Selçuk University, Konya, Turkey.N. Yilmaz, MD, Associate Professor, Rheumatology Department, Faculty of Medicine, Istanbul Bilim University; H. Emmungil, MD; S. Gucenmez, MD, Rheumatology Department, Faculty of Medicine, Ege University; G. Ozen, MD, Rheumatology Department, Faculty of Medicine, Marmara University; F. Yildiz, MD, Rheumatology Department, Faculty of Medicine, Cukurova University; A. Balkarli, MD, Rheumatology Department, Faculty of Medicine, Pamukkale University; G. Kimyon, MD, Faculty of Medicine, Gaziantep Rheumatology University; B.N. Coskun, MD, Rheumatology Department, Faculty of Medicine, Uludag University; I. Dogan, MD, Rheumatology Department, Faculty of Medicine, Hacettepe University; O.N. Pamuk, MD, Rheumatology Department, Faculty of Medicine, Trakya University; S. Yasar, MD, Rheumatology Department, Faculty of Medicine, Eskişehir Osmangazi University; G.Y. Cetin, MD, Rheumatology Department, Faculty of Medicine, Kahramanmaraş Sütçüimam University; A. Yazici, MD, Associate

PMID: 26178288
DOI: 10.3899/jrheum.150065

Abstract

Objective: To assess bladder toxicity of cyclophosphamide (CYC) and uroprotective effect of mesna in rheumatic diseases.

Methods: Data of 1018 patients (725 women/293 men) treated with CYC were evaluated in this retrospective study. All of the following information was obtained: the cumulative CYC dose, route of CYC administration, duration of therapy, concomitant mesna usage, and hemorrhagic cystitis. Cox proportional hazard model was used for statistics.

Results: We identified 17 patients (1.67%) with hemorrhagic cystitis and 2 patients (0.19%) with bladder cancer in 4224 patient-years. The median time for diagnosis to hemorrhagic cystitis was 10 months (4-48) and bladder cancer was 8 years (6-10.9). There were 583 patients (57.2%) who received mesna with intravenous CYC therapy. We observed similar incidence rate for hemorrhagic cystitis in both patient groups concomitantly treated with or without mesna [9/583 (1.5%) vs 8/425 (1.8%) respectively, p = 0.08]. Cumulative CYC dose (HR for 10-g increments 1.24, p < 0.001) was associated with hemorrhagic cystitis.

Conclusion: Cumulative dose was the only risk factor for hemorrhagic cystitis in patients treated with CYC. No proof was obtained for the uroprotective effect of mesna in our cohort.

Keywords: HEMORRHAGIC CYSTITIS; MESNA; RHEUMATIC DISEASES.

MeSH terms

Adult
Aged
Cyclophosphamide / adverse effects*
Cyclophosphamide / therapeutic use
Cystitis / chemically induced
Cystitis / epidemiology*
Female
Humans
Incidence
Male
Mesna / therapeutic use*
Middle Aged
Protective Agents / therapeutic use*
Rheumatic Diseases / drug therapy*
Treatment Outcome

Substances

Protective Agents
Cyclophosphamide
Mesna