Incidence of hemorrhagic cystitis after cyclophosphamide therapy with or without mesna: A cohort study and comprehensive literature review (original) (raw)
Related papers
Journal of Urology, 1997
The aim of this research was to compare the protective effects of mesna, hyperbaric oxygenation (HBO), and their combination in cyclophosphamide-induced hemorrhagic cystitis in guinea pigs. Following one dose of i.p. 21.5 mg./kg. mesna administration 20 minutes before i.p. 68.1 mg./kg. cyclophosphamide, 3 additional doses of mesna were given every three hours. A total of 8 HBO exposures, 5 of which were applied prophylactically before cyclophosphamide, were performed at 2.8 ATA for 90 minutes 2 times a day. Although mesna or HBO provided significant protection for cyclophosphamide-cystitis in animal bladders, there was also significant damage compared with controls. The combination of mesna and HBO, which act through independent mechanisms, resulted in complete protection, since mean histological scores and hematuria levels in this group were not different from controls (p >0.05). Therefore, this combination may be a useful tool in the prophylaxis and treatment of cyclophosphamide-induced hemorrhagic cystitis.
Prevention and treatment of cyclophosphamide and ifosfamide-induced hemorrhagic cystitis
Journal of Molecular Pathophysiology, 2012
Free radicals and non-radical reactive molecules as well as several cytokines (e.g. tumor necrosis factor-α and interleukin family) and transcription factors (e.g. nuclear factor-κB and activator protein-1) are now known to take part in the pathogenesis of cyclophosphamide (CP) and ifosfamide (IF) induced hemorrhagic cystitis (HC). When these molecular factors are taken into account pathogenesis of bladder toxicity can be summarized in three steps: (1) acrolein rapidly enters into the uroepithelial cells, (2) activates intracellular ROS and NO production (directly or through transcription factors) leading to peroxynitrite production, and (3) finally the elevated peroxynitrite level basically damages lipids (lipid peroxidation), proteins (protein oxidation) and DNA (strand breaks) leading to PARP activation, a DNA repair enzyme. DNA damage causes PARP overactivation, resulting in the depletion of oxidized nicotinamide adenine dinucleotide (NAD+) and adenosine triphosphate (ATP), and consequently in necrotic cell death. There is no doubt that for an effective prevention against CP-and IF-cystitis all pathophysiological mechanisms must be taken into consideration. Experimental works reporting beneficial effects of antioxidants, iNOS inhibitors, cytokine blockers or hyperbaric oxygen (HBO) treatment, against CP-and/or IF-induced HC exist in literature. In this article, we discussed the possible mechanisms and effectiveness of agents used in addition to mesna to prevent CP-and IF-cystitis. In conclusion, antioxidants, iNOS inhibitors, peroxynitrite scavengers, anti-inflammatory agents, as well as HBO therapy may be added to mesna administration in clinical trials in order to obtain the best protocol to improve quality of patients comfort
Indian Journal of Cancer, 2006
BACKGROUND: Hemorrhagic cystitis (HC) is a dose limiting side effect of cyclophosphamide (CYP). AIM: In this study, we aimed to investigate the role of amifostine in the protection of CYP-induced HC and compare its efficacy with mesna. SETTING AND DESIGN: This animal study was conducted in the Experimental Animals Breeding and Research Center of the Medical Faculty of Uludag University. MATERIALS AND METHODS: Male Wistar rats (150-200 g; 10 rats per group) were randomly assigned to four groups. Group I (control group) received no drugs, group II received CYP (200 mg/kg, i.p.) alone, group III received amifostine (200 mg/kg, i.p.) and CYP, and group IV received CYP and mesna (40 mg/kg, i.p.) immediately and 4 and 8 h after administration of CYP. Bladders of animals were assessed macroscopically and histologically 24 h later. Gross assessment for presence of edema and hemorrhage and histological evaluation of damage to the bladder were scored according to Gray's criteria. STATISTICAL ANALYSIS USED: For macroscopic and microscopic data, we used statistical evaluation by Kruskal-Wallis nonparametric analysis of variance followed by the Mann-Whitney U-test. RESULTS: All the animals in group II had evidence of HC. Significant histological damage and macroscopic changes were present in this group compared to control group (P<0.001). The median scores for bladder damage in group III and IV were significantly lower compared to group II (P<0.001). When the median scores for bladder damage of group I, III, and IV were compared, there was no significant difference among these groups. CONCLUSION: This study demonstrated the efficacy of amifostine in prevention of cyclophosphamide-induced hemorrhagic cystitis.
Low‐Dose Cyclophosphamide Associated with Hemorrhagic Cystitis in a Breast Cancer Patient
The Breast …, 2011
Hemorrhagic cystitis is a known complication of high-dose cyclophosphamide treatment, generally occurring at doses greater than 100 g. There are few reports of hemorrhagic cystitis occurring with low-dose cyclophosphamide therapy, and this complication has not been described in breast cancer patients. We present a case of a patient with stage IIB breast cancer who developed clinical, radiographic, and pathologic evidence of hemorrhagic cystitis after a single 600 mg ⁄ m 2 dose of cyclophosphamide. Three subsequent cycles of cyclophosphamide with the addition of IV hydration and MESNA were given without complication, and the patient's urologic symptoms resolved. Repeat cystoscopy demonstrated pathologic resolution of the cystitis. We review the literature regarding proposed mechanisms of hemorrhagic cystitis, and discuss the applicability of these hypotheses in our patient. n
Bone marrow transplantation, 2015
Hemorrhagic cystitis (HC) secondary to Cyclophosphamide (CTX) is seen in 5-25% of cases who underwent hematopoietic stem cell transplantation (HSCT), in which acrolein is the major causative agent. 1 Late HC was reported in up to 58% of patients receiving myeloablative conditioning for haplo-identical and cord blood HSCT. 1 MESNA (2-mercaptoethanesulfonic acid) has a sulfhydryl group that can combine with acrolein and deactivate it. 2-4 The instruction recommends injection of MESNA rapidly, intermittently at the intervals of 0, 4 and 8 h after CTX, with the dose of 150% of the daily dosage of CTX. However, traditional treatments could not provide efficient protection of the bladder. Irrespective of the increasing dosage of MESNA administration, it is hard to maintain an effective concentration for 10-12 h post infusion. We tried to prove whether continuous IV MESNA could decrease the incidence of HC in HSCT or not.
The Journal of Rheumatology, 2015
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...
Use of dexamethasone with mesna for the prevention of ifosfamide-induced hemorrhagic cystitis
International Journal of Urology, 2003
Aim : Hemorrhagic cystitis (HC) is a limiting side-effect of chemotherapy with ifosfamide (IFS). In the study presented here, we investigated the use of dexamethasone in combination with mesna for the prevention of IFS-induced HC. Methods : Male Wistar rats (150-200 g; 6 rats per group) were treated with saline or mesna 5 min (i.p.) before and 2 and 6 h after (v.o.) administration of IFS. One, two or three doses of mesna were replaced with dexamethasone alone or with dexamethasone plus mesna. Cystitis was evaluated 24 h after its induction by the changes in bladder wet weight and by macroscopic and microscopic analysis. Results : The replacement of the last dose or the last two doses of mesna with dexamethasone reduced the increase in bladder wet weight induced by IFS by 84.79% and 89.13%, respectively. In addition, it almost abolished the macroscopic and microscopic alterations induced by IFS. Moreover, the addition of dexamethasone to the last two doses of mesna was more efficient than three doses of mesna alone when evaluated microscopically. Conclusion : Dexamethasone in combination with mesna was efficient in blocking IFS-induced HC. However, the replacement of last two doses of mesna with saline or all of the mesna doses with dexamethasone did not prevent HC.
The Journal of Urology, 2001
Purpose: Hyperbaric oxygen therapy and mesna have been successfully used for hemorrhagic cystitis. We defined the protective effects of hyperbaric oxygen and mesna in further cyclophosphamide induced hemorrhagic cystitis in guinea pigs. Materials and Methods: A total of 48 male guinea pigs were divided into 6 groups. All groups received 2 doses of 68.1 mg./kg. cyclophosphamide intraperitoneally at the same time intervals but group 1 served as controls. Group 2 received cyclophosphamide only, group 3 received hyperbaric oxygen treatment (2.8 ATA for 90 minutes twice daily) before and the day after further cyclophosphamide, group 4 received 21.5 mg./kg. mesna intraperitoneally only with further cyclophosphamide, group 5 received hyperbaric oxygen and mesna with further cyclophosphamide, and group 6 received hyperbaric oxygen before initial cyclophosphamide, between the 2 doses and after the further dose of cyclophosphamide, and mesna on the days of cyclophosphamide. Results: Although mesna alone provided protection against cyclophosphamide induced cystitis in animal bladders, there was also significant damage compared with controls. When the uroprotective efficacy of mesna was supported with hyperbaric oxygen, bladder protection was promoted since mean histological scores and hematuria levels in this group did not differ from those in controls. Conclusions: According to this animal study using hyperbaric oxygen as adjuvant therapy in humans may be a better tool than mesna alone for the prophylaxis and treatment of cyclophosphamide induced hemorrhagic cystitis.