Skip to main content
SpringerLink
Log in

Histological changes in bladders of patients submitted to ifosfamide chemotherapy even with mesna prophylaxis

  • Original Article
  • Published:
Cancer Chemotherapy and Pharmacology Aims and scope Submit manuscript

Abstract

Purpose

Hemorrhagic cystitis (HC) is a limiting side effect of chemotherapy with ifosfamide (IFS). Mesna is the drug of choice for prevention of HC. In this study, we analyzed cystoscopic and histological changes present in bladders of patients using IFS with mesna prophylaxis.

Methods

Thirty-three patients selected for IFS plus three doses of mesna chemotherapy regime were assigned at random to two groups: Group I or reference group consisted of 18 patients yet untreated. Group II consisted of 15 patients in whom urinalysis and cystoscopy plus vesical biopsy were performed only 24 h after receiving the last dose of IFS. The cystoscopic and histological findings were used as parameters for evaluating the results. For the former the criterion adopted was macroscopic vesical changes in accordance with Gray’s criteria. Histological analyses were performed by evaluation method especially adapted to this study.

Results

Even under treatment with three doses of mesna, 66.7% of patients presented cystoscopic alterations and 100% showed bladder mucosa microscopic alterations such as edema, exocytosis, and hemorrhage.

Conclusions

The standard protocol used for prevention of IFS-induced HC with three doses of mesna does not completely prevent bladder damage. The histopathological criteria used in this study for observation of inflammatory events allowed staging the intensity of IFS-induced urothelial and mucosal injury.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Brade WP, Herdrich K, Varini M (1985) Ifosfamide—pharmacology, safety and therapeutic potential. Cancer Treat Rev 12:1

    Article  PubMed  CAS  Google Scholar 

  2. Brock N, Pohl J (1983) The development of mesna for regional detoxification. Cancer Treat Rev 10:33–43

    Article  PubMed  Google Scholar 

  3. Burket H (1983) Clinical overview of mesna. Cancer Treat Rev 10(Suppl A):175–181

    Article  Google Scholar 

  4. Cox PJ (1979) Cyclophosphamide cystitis—identification of acrolein as the causative agent. Biochem Pharmacol 28:2045–2049

    Article  PubMed  CAS  Google Scholar 

  5. Dechant KL, Brogden RN, Pilkington T, Faulds D (1991) Ifosfamide/Mesna. A review of its antineoplastic activity, pharmacokinetic properties and therapeutic efficacy in cancer. Drugs 42:428–467

    Article  PubMed  CAS  Google Scholar 

  6. Etlik O, Tomur A, Deveci S, Piskin I, Pekcan M (1997) Comparison of uroprotective efficacy of Mesna and HBO treatments in cyclophosphamide-induced hemorrhagic cystitis. J Urol 158:2296–2299

    Article  PubMed  CAS  Google Scholar 

  7. Foad BSI, Hess EV (1976) Urinary bladder complications with cyclophosphamide therapy. Arch Intern Med 136:616–619

    Article  PubMed  CAS  Google Scholar 

  8. Gomes TNA, Santos CC, Souza-Filho MVP, Cunha FQ, Ribeiro RA (1995) Participation of TNF-α and IL-1 in the pathogenesis of cyclophosphamide-induced hemorrhagic cystitis. Braz J Med Biol Res 28:1103–1108

    PubMed  CAS  Google Scholar 

  9. Hensley ML, Schuchter ML, Lindley C, Meropol NJ et al (1999) American Society of Clinical Oncology clinical practice guidelines for the use of chemotherapy and radiotherapy protectants. J Clin Oncol 17:3333–3355

    PubMed  CAS  Google Scholar 

  10. Higgs D, Nagy C, Einhorn LH (1989) Ifosfamide: a clinical review. Semin Oncol Nurs 5:70–77

    Article  PubMed  CAS  Google Scholar 

  11. Hu VY, Malley S, Dattilio A, Folsom SB, Zvara P, Vizzard MA (2003) COX-2 and prostanoid expression in micturition pathways after cyclophosphamide-induced cystitis in the rat. Am J Physiol Regul Integr Comp Physiol 284:574–585

    Google Scholar 

  12. Gray KJ, Engelmann UH, Johnson EH, Fishman IJ (1986) Evaluation of misoprostol cytoprotection of the bladder with cyclophosphamide (Cytoxan) therapy. J Urol 133:497–500

    Google Scholar 

  13. Katz A, Epelman S, Anelli A et al (1995) A prospective randomized evaluation of three schedules of mesna administration in patients receiving an ifosfamide-containing chemotherapy regimen: sustained efficiency and simplified administration. J Cancer Res Clin Oncol 121:128–131

    Article  PubMed  CAS  Google Scholar 

  14. Mace JR, Keohan ML, Bernardy H, Junge K, Niebch G et al (2003) Crossover randomized comparison of intravenous versus intravenous/oral mesna in soft tissue sarcoma treated with high-dose ifosfamide. Clin Cancer Res 9:5829–5834

    PubMed  CAS  Google Scholar 

  15. Morais MM, Belarmino-Filho JN, Brito GAC, Ribeiro RA (1999) Pharmacological and histopathological study of cyclophosphamide-induced hemorrhagic cystitis—comparison of the effects of dexamethasone and Mesna. Braz J Med Biol Res 32:1211–1215

    Article  PubMed  CAS  Google Scholar 

  16. Pyeritz R, Droller MJ, Bender WL, Saral R (1978) An approach to control of massive hemorrhage in cyclophosphamide-induced cystitis by intravenous vasopressin: a case report. J Urol 120:253–254

    PubMed  CAS  Google Scholar 

  17. Ratliff TR, Willians RD (1998) Hemorrhagic cystitis, chemotherapy, and bladder toxicity. J Urol 159:1044

    Article  PubMed  CAS  Google Scholar 

  18. Ribeiro RA, Freitas HC, Campos MC et al (2002) Tumor necrosis factor-α and interleukin-1β mediate the production of nitric oxide involved in the pathogenesis of ifosfamide induced hemorrhagic cystitis in mice. J Urol 150:2229–2234

    Google Scholar 

  19. Shepherd JD, Pringle LE, Barnett MJ, Klingemann HG, Reece DE, Phillips GL (1991) Mesna versus hyperhydration for the prevention of cyclophosphamide-induced hemorrhagic cystitis in bone marrow transplantation. J Clin Oncol 11:2016–2020

    Google Scholar 

  20. Souza-Filho MVP, Lima MVA, Pompeu MML, Ballejo G, Cunha FQ, Ribeiro RA (1997) Involvement of nitric oxide in the pathogenesis of cyclophosphamide-induced hemorrhagic cystitis. Am J Pathol 150:247–256

    CAS  Google Scholar 

  21. Theman H, Oberdorf E, Brock N, Pohl J (1987) Electron microscopic investigations of cyclophosphamide-induced lesions of the urinary bladder of the rat and their prevention by mesna. Urol Int 42:37–43

    Article  Google Scholar 

  22. Vieira MM, Brito GA, Belarmino-Filho JN, Macedo FY, Nery EA, Cunha FQ, Ribeiro RA (2003) Use of dexamethasone with mesna for the prevention of ifosfamide-induced hemorrhagic cystitis. Int J Urol 10(11):595–602

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Surgery, Division of Urology, Cancer Institute of Ceará, Fortaleza, Brazil

    Marcos Venício Alves Lima

  2. Department of Pathology, Cancer Institute of Ceará, Fortaleza, Brazil

    Francisco Valdeci Ferreira

  3. Department of Physiology and Pharmacology, Faculty of Medicine, Universidade Federal do Ceará, Fortaleza, Brazil

    Francisco Yuri Bulcão Macedo & Ronaldo Albuquerque Ribeiro

  4. Department of Morphology, Faculty of Medicine, Universidade Federal do Ceará, Fortaleza, Brazil

    Gerly Anne de Castro Brito

  5. Department of Clinical Oncology, Cancer Institute of Ceará, Fortaleza, Brazil

    Ronaldo Albuquerque Ribeiro

  6. Centro de Biomedicina, Faculdade de Medicina, Universidade Federal do Ceará, Rua Cel. Nunes de Melo, 1315, Caixa Postal 3229, 60430-270, Fortaleza, CE, Brazil

    Ronaldo Albuquerque Ribeiro

Authors
  1. Marcos Venício Alves Lima
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Francisco Valdeci Ferreira
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Francisco Yuri Bulcão Macedo
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Gerly Anne de Castro Brito
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ronaldo Albuquerque Ribeiro
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ronaldo Albuquerque Ribeiro.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lima, M.V.A., Ferreira, F.V., Macedo, F.Y.B. et al. Histological changes in bladders of patients submitted to ifosfamide chemotherapy even with mesna prophylaxis. Cancer Chemother Pharmacol 59, 643–650 (2007). https://doi.org/10.1007/s00280-006-0307-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00280-006-0307-5

Keywords

Search

Navigation