mesna and Urinary-Bladder-Neoplasms

Topics: Antirheumatic Agents; Cyclophosphamide; Cystitis; Databases, Bibliographic; Humans; Incidence; Mesna; Protective Agents; Rheumatic Diseases; Urinary Bladder Neoplasms

We have carried out a phase II study in advanced or metastatic transitional cell carcinoma of the bladder. Eligible patients had unresectable bladder cancer, previously treated with one line of systemic chemotherapy. Treatment consisted of ifosfamide 1000 mg/sm in a 2-hour infusion for 5 consecutive days from d.1 to d.5. Mesna was administered intravenously at a 20% of the ifosfamide dosage before ifosfamide and orally at 40% after 4 and 8 hours from the ifosfamide infusion. Twenty patients entered the study and received a total of 62 cycles: the treatment resulted feasible on an outpatient basis, with mild toxicity. Only one partial response was observed. With this dose and schedule, ifosfamide appeared less effective than in a previous report at higher doses. Toxicity was acceptable.

Topics: Administration, Oral; Aged; Alopecia; Ambulatory Care; Antineoplastic Agents, Alkylating; Bone Marrow; Carcinoma, Transitional Cell; Cause of Death; Disease Progression; Drug Administration Schedule; Expectorants; Feasibility Studies; Female; Humans; Ifosfamide; Infusions, Intravenous; Lymphatic Metastasis; Male; Mesna; Middle Aged; Nausea; Neoplasm Staging; Remission Induction; Survival Rate; Urinary Bladder Neoplasms; Vomiting

Carcinoma of the bilharzial bladder, the most common cancer in Egyptian patients has been, until recently, largely treated by surgery. We have studied the activity of a series of single agents in phase II trials and identified a number of active agents. Here we report the results of a trial in which therapeutic combinations of the most active agents were administered in alternating cycles to patients who had never received chemotherapy.. The study included 30 patients with histologically proven inoperable (20), recurrent (5, 2 of whom subsequently developed metastases), or metastatic disease (5). There were 27 males and 3 females, with a median age of 48.5 years (range 29-65 years). Fourteen patients had squamous cell carcinoma, 12 had transitional cell carcinoma, 2 had adenocarcinoma, and the remaining 2 had undifferentiated carcinoma. Chemotherapy consisted of epidoxorubicin (120 mg/sqm i.v. d1) and vincristine (1.4 mg/sqm i.v., days 1 and 8) alternating with etoposide (100 mg/sqm i.v. infusion over 1 hour, days 1 to 5) and ifosfamide (1800 mg/sqm i.v. infusion over 2 hours, days 1 to 5). Mesna was given as a uroprotector at 40% of the ifosfamide dose at 0, 4, and 8 hours after the ifosfamide infusion. Courses were repeated every 3-4 weeks.. Among the 22 evaluable patients, 8 (36.5%) had a partial and one (4.5%), a complete response, giving a response rate of 46%. Three more patients had responses that were less than a partial remission, and 6 patients showed disease stabilisation on chemotherapy. Toxicities were tolerable and consisted mainly of myelosuppression. Results were further analysed in relation to pathologic subtype, disease status at the start of chemotherapy, and the delivered dose intensity. No relationship was found between any of these parameters and response to therapy.. Advanced bilharzial bladder cancer is relatively sensitive to combination chemotherapy, but complete remission and prolonged survival is rare in this subgroup of patients with advanced disease. Further studies will be needed to determine the relative efficacy of single agents and drug combinations.

Topics: Adult; Aged; Antibiotics, Antineoplastic; Antineoplastic Agents, Alkylating; Antineoplastic Agents, Phytogenic; Antineoplastic Combined Chemotherapy Protocols; Dose-Response Relationship, Drug; Doxorubicin; Etoposide; Female; Humans; Ifosfamide; Male; Mesna; Middle Aged; Schistosomiasis; Survival Rate; Treatment Outcome; Urinary Bladder Neoplasms; Vincristine

Transitional cell carcinoma is the most common bladder cancer of dogs. Cisplatin combined with piroxicam provides superior response rates, but unacceptable rates of nephrotoxicity. Tavocept is a chemoprotectant that has mitigated cisplatin toxicity and decreased the required infusion/diuresis volume in clinical trials in humans.. We hypothesized that Tavocept would decrease diuresis volume and time and facilitate safe administration of a cisplatin/piroxicam protocol to dogs with bladder cancer. Secondary objectives were to compare response rate and survival times to an historical comparator group treated without Tavocept.. Fourteen client-owned dogs were prospectively enrolled.. Tumor volume was measured by computed tomography at days 0, 42, and 84. Dogs received combination Tavocept/cisplatin with a shortened diuresis protocol. A total of 4 doses was planned, with concurrent administration of piroxicam. Serial biochemical analyses were evaluated for azotemia.. A 90-minute infusion/diuresis time was used for all dogs. Three dogs (21%) had concurrent increases in serum creatinine (>2.0 mg/dL) and BUN (>42 mg/dL) concentrations; 2 of these dogs were isosthenuric. This frequency of nephrotoxicity is significantly less (P = 0.0406) than that of an historical control group treated without Tavocept. Overall response rate was 27%. Median survival time was comparable to historical controls (253 vs. 246 days).. Tavocept decreased the required diuresis time with cisplatin from > 6 hours to 90 minutes, while also decreasing occurrence of azotemia. Survival time was comparable, but the response rate was inferior to an historical comparator group. Further evaluation in other tumors susceptible to platinum agents is warranted.

Topics: Animals; Antineoplastic Agents; Blood Urea Nitrogen; Carcinoma, Transitional Cell; Cisplatin; Creatinine; Diuresis; Dog Diseases; Dogs; Drug Therapy, Combination; Mesna; Piroxicam; Prospective Studies; Renal Insufficiency; Treatment Outcome; Urinary Bladder Neoplasms

Batracylin (NSC-320846) is a dual inhibitor of DNA topoisomerases I and II. Batracylin advanced as an anticancer agent to Phase I clinical trials where dose limiting hemorrhagic cystitis (bladder inflammation and bleeding) was observed. To further investigate batracylin's mechanism of toxicity, studies were conducted in Fischer 344 rats. Once daily oral administration of 16 or 32 mg/kg batracylin to rats for 4 days caused overt toxicity. Abnormal clinical observations and adverse effects on clinical pathology, urinalysis, and histology indicated acute renal damage and urothelial damage and bone marrow dysfunction. Scanning electron microscopy revealed sloughing of the superficial and intermediate urothelial layers. DNA damage was evident in kidney and bone marrow as indicated by histone γ-H2AX immunofluorescence. After a single oral administration of 16 or 32 mg/kg, the majority of batracylin was converted to N-acetylbatracylin (NAB) with a half-life of 4 hr to 11 hr. Mesna (Mesnex™), a drug known to reduce the incidence of hemorrhagic cystitis induced by ifosfamide or cyclophosphamide, was administered to rats prior to batracylin, but did not alleviate batracylin-induced bladder and renal toxicity. These findings suggest that batracylin results in DNA damage-based mechanisms of toxicity and not an acrolein-based mechanism of toxicity as occurs after ifosfamide or cyclophosphamide administration.

Topics: Animals; Biomarkers, Tumor; Body Weight; Female; Glycosuria; Histones; Kidney Neoplasms; Male; Mesna; Phosphoproteins; Quinazolines; Random Allocation; Rats; Urinary Bladder Neoplasms

A 56-year-old man was admitted to our hospital for salvage chemotherapy of recurrent diffuse large B cell malignant lymphoma at clinical stage IIIb and which had been treated with 6 cycles of cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP). Computed tomography showed multiple tumors in the bladder after a cycle of ifosfamide, etoposide and mitoxantrone (MINE), but cystoscopy after the second cycle revealed a single non-papillary tumor about 1cm in diameter. After 3 cycles of MINE therapy, transurethral resection of bladder tumor was performed. At the time of the operation, the protruded lesion disappeared and there remained only a scar. Biopsy of the scar revealed malignant lymphoma infiltrated into the submucosal layer. Although the rate of the bladder involvement of malignant lymphoma reaches 3-20% in autopsy cases, it is very rare for a secondary malignant lymphoma of the urinary bladder to be diagnosed clinically. The prognosis of the secondary bladder lymphoma is much poorer than that of the primary one, because of the widespread dissemination of the disease at the time of diagnosis.

Topics: Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Cyclophosphamide; Doxorubicin; Drug Administration Schedule; Etoposide; Humans; Ifosfamide; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse; Male; Mesna; Middle Aged; Mitoxantrone; Prednisone; Urinary Bladder Neoplasms; Vincristine

Topics: Cyclophosphamide; Granulomatosis with Polyangiitis; Humans; Immunosuppressive Agents; Mesna; Protective Agents; Urinary Bladder Neoplasms

The effects of 2-mercaptoethane sulfonate (MESNA) and phenethyl and 6-phenylhexyl isothiocyanates (PEITC and PHITC) on urinary bladder tumorigenesis were investigated in Wistar rats treated with N-butyl-N-(4-hydroxybutyl)nitrosamine (BHBN). A total of 190 male rats were divided into eight groups. Animals in groups 1, 3 and 4 were administered BHBN in drinking water (0.025%) and group 2 rats were given 0.025% BHBN plus 0.05% MESNA solution for 15 weeks. Rats in groups 3 and 4 were fed a diet supplemented with PEITC or PHITC at a dose level of 0.5 micromol/g for 16 weeks starting 1 week prior to the BHBN treatment. Rats in groups 5-7 served as MESNA, PEITC or PHITC alone controls. Group 8 served as a non-treatment control. The chromatographic profile of drinking water for group 2 animals indicated no chemical interaction between BHBN and MESNA. The incidences of papillomas in the bladder and total bladder tumors including transitional cell carcinomas were significantly (P<0.01) reduced in group 2 as compared to that in group 1. The multiplicities of papillomas or total bladder tumors were significantly (P<0.01) lower in group 2 and 4 rats treated with MESNA and PHITC, respectively, than in group 1 rats. The PEITC treatment, however, did not affect the BHBN-induced bladder tumorigenesis. No bladder tumors were found in animals of groups 5-8. The results in the present study clearly indicate that both MESNA and PHITC are potent chemopreventive agents against bladder tumor development in rats induced by BHBN.

Topics: Animals; Butylhydroxybutylnitrosamine; Carcinogens; Isothiocyanates; Male; Mesna; Models, Chemical; Protective Agents; Rats; Rats, Wistar; Urinary Bladder; Urinary Bladder Neoplasms

Sodium 2-mercaptoethane sulfonate (Mesna) reacts with urotoxic metabolites of oxazaphosphorine drugs (e.g. cyclophosphamide or ifosfamide) and has been used clinically to protect against damage induced by these aggressive anti-neoplastic drugs in the kidney and lower urinary and genital tracts. Ochratoxin A (OTA) is a potent nephrotoxin in several species. In order to elucidate whether mesna has curative or preventive effects on OTA-induced renal damage or renal tumor development, we administered OTA and/or mesna to both DA and Lewis rats for their life-time and examined kidney, urethra and urinary bladder histologically. OTA induced sex- and strain-specific renal tumors. However, there was no evidence of any effect of mesna on the incidence and distribution of any type of tumor or non-neoplastic finding in the kidney in either strain or treated group. In this study, we have confirmed that mesna treatment did not show any curative or preventive effects on either OTA-induced kidney damage or renal tumor development in two different strains that have distinct metabolic characteristics.

Topics: Animals; Body Weight; Carcinogens; Female; Kidney Neoplasms; Male; Mesna; Ochratoxins; Organ Size; Protective Agents; Random Allocation; Rats; Rats, Inbred Lew; Sex Factors; Urethral Neoplasms; Urinary Bladder Neoplasms

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Carcinoma, Small Cell; Etoposide; Hematuria; Humans; Ifosfamide; Male; Mesna; Quadriplegia; Urinary Bladder Neoplasms

Urinary bladder cancers following prolonged cyclophosphamide therapy are being increasingly reported. We report a case of transitional cell carcinoma of the urinary bladder occurring 12 years after pulse intravenous therapy with cyclophosphamide for Hodgkin's disease. The mechanism of bladder carcinogenesis and the possible role of the uroprotector MESNA in preventing cyclophosphamide induced bladder cancer are discussed.

Topics: Cyclophosphamide; Hodgkin Disease; Humans; Male; Mesna; Middle Aged; Neoplasms, Second Primary; Urinary Bladder Neoplasms

Twenty rats were randomized into a vesicosigmoidostomy and an unoperated control group. In both groups the 24 hour excretion of secondary amines, nitrate, nitrite and nitrosamines was measured before and after gavage of proline and nitrate, piperazine and nitrate, N-nitrosoproline, mono-N-nitrosopiperazine. The urinary nitrosamine concentrations were not significantly different between both groups neither before nor after application of the several substances. Thirty rats were randomized into two vesicosigmoidostomy groups with and without antibiotic coverage and an unoperated control group. After ligation of distal rectum and mesosigmoid the rectosigmoids were removed. No significant concentrations of volatile nitrosamines could be measured in the rectosigmoid contents of the three groups. One hundred and twenty rats randomized into three groups following vesicosigmoidostomy received the potential nitrosamine antidotes sodium-2-mercaptoethane sulfonate or sodiumpentosan-polysulfate or acted as controls. 12/118 (10.2%) developed adenomas and 25/118 (21.2%) adenocarcinomas at the vesico-colonic anastomosis with no significant differences between the three groups concerning tumor incidence or mortality. The results show that colon carcinomas occur in a rat model for ureterosigmoidostomy without evidence for thus induced nitrosamine formation. This and the missing effect of nitrosamine antidotes suggest that other factors than nitrosation must be responsible for colon carcinogenesis following urinary diversion via intestine.

Topics: Adenocarcinoma; Adenoma; Amines; Anastomosis, Surgical; Animals; Colon, Sigmoid; Colonic Neoplasms; Feces; Female; Mesna; Nitrates; Nitrites; Nitrosamines; Pentosan Sulfuric Polyester; Rats; Rats, Inbred Strains; Rectum; Urinary Bladder Neoplasms; Urinary Diversion

This study describes the prolonged survival of male SD-rats that bear bladder carcinomas induced either with 44 mg/kg or 28 mg/kg of N-nitroso-N-butyl-N-(4-hydroxybutyl)amine (BBNOH), when daily doses of 350 mg/kg of sodium-2-mercaptoethane sulfonate (mesna) were administered concomitantly. The difference to carcinogen-treated positive controls was highly significant (P = 0.0009 and 0.0013, respectively). Tumor volumes at time of death (P less than 0.005) and frequency of metastases were also reduced in rats that received both compounds in comparison to BBNOH-treated animals.

Topics: Animals; Butylhydroxybutylnitrosamine; Male; Mercaptoethanol; Mesna; Neoplasm Metastasis; Rats; Urinary Bladder Neoplasms

Urotoxic side effects, particularly haemorrhagic cystitis, have been a limiting factor for the therapeutic use of the oxazaphosphorine cytostatics cyclophosphamide, ifosfamide and trofosfamide. The development of mesna (Uromitexan) has made it possible to carry out regional detoxification in the kidneys and the efferent urinary tract and thus to achieve clinically prophylaxis against the urotoxic side effects of oxazaphosphorines. In the body, mesna is rapidly converted to the biologically inactive disulfide form (dimesna). After glomerular filtration, dimesna is reduced by interaction with the glutathione system of the renal tubular cells and is excreted in the urine as mesna, the free thiol compound. This compound is then capable of definitively detoxifying the oxazaphosphorine metabolites in the urine. In extensive experiments on rats, it has been demonstrated that the cyclophosphamide-induced occurrence of urinary bladder tumours could be reduced or even eliminated by simultaneous administration of mesna. Detoxification by mesna enables the clinical use of higher doses and, consequently, a possible increase in therapeutic efficiency.

Topics: Animals; Biotransformation; Cyclophosphamide; DNA; Glutathione; Ifosfamide; Kidney; Leukemia, Experimental; Mercaptoethanol; Mesna; Rats; Structure-Activity Relationship; Urinary Bladder; Urinary Bladder Neoplasms

Topics: Cyclophosphamide; Drug Interactions; Humans; Ifosfamide; Infusions, Parenteral; Mercaptoethanol; Mesna; Urinary Bladder Neoplasms

The influence of sodium-2-mercaptoethanesulphonate (Mesna) on urinary bladder cancer induced by N-nitroso-N-butyl-N-(4-hydroxybutyl)amine (BBNOH) was studied in male Sprague-Dawley rats. The treatment consisted of 5 g/kg BBNOH per gavage and 63 g/kg Mesna in drinking water over a period of 39 weeks. A positive control group was given the same dose of BBNOH as the treated group. Although Mesna did not reduce the incidence of bladder carcinomas, it significantly increased the lifespan of the animals, thus suggesting a partial general protective action.

Topics: Animals; Body Weight; Butylhydroxybutylnitrosamine; Carcinogens; Drinking; Lung Neoplasms; Male; Mercaptoethanol; Mesna; Nitrosamines; Rats; Rats, Inbred Strains; Time Factors; Urinary Bladder Neoplasms

An experimental model was developed, in which urinary bladder cancer was induced by cyclophosphamide in rats, thus reproducing cyclophosphamide-induced urinary bladder carcinogenesis observed in humans. It was possible in this model to achieve a highly significant reduction of cyclophosphamide-induced urinary bladder cancer by concomitant administration of sodium 2-mercaptoethane sulfonate (mesna). A significant delay of urinary bladder carcinogenesis by administration of the uroprotective substance mesna was also observed when using butylbutanolnitrosamine for inducing urinary bladder cancer. It was thus for the first time possible to assure chemoprevention of this tumor type by administration of a specific antidote.

Topics: Animals; Carcinoma, Transitional Cell; Cyclophosphamide; Dose-Response Relationship, Drug; Female; Male; Mercaptoethanol; Mesna; Papilloma; Rats; Rats, Inbred Strains; Urinary Bladder Neoplasms

Cyclophosphamide (CP) was administered orally at a dose of 2.5 mg/kg body weight five times a week to 300 male Sprague-Dawley rats in a carcinogenicity experiment. Four groups of 50 rats were treated with two different doses of sodium 2-mercaptoethane sulfonate (mesna, Uromitexan) (single doses of 5 or 15 mg/kg body weight), or disodium 2,2'-dithio-bis-ethane sulfonate (dimesna) (single doses of 12 or 35 mg/kg body weight), and the effect on carcinogenicity by cyclophosphamide was investigated. Two groups received mesna or dimesna only, and one additional group of 100 rats served as an untreated control. Evaluation of the study after 20 months proved CP to be carcinogenic, the induced neoplasms being in a variety of organs including tumors of the urinary bladder in 30% of the rats. The additional administration of mesna and dimesna significantly reduced the bladder tumor risk, this reduction being dose-related. In the 100 rats treated with mesna or dimesna only, no evidence of a carcinogenic response or signs of other toxic effects were observed.

Topics: Animals; Cyclophosphamide; Dose-Response Relationship, Drug; Male; Mercaptoethanol; Mesna; Neoplasms, Experimental; Rats; Rats, Inbred Strains; Risk; Urinary Bladder Neoplasms

Topics: Animals; Cyclophosphamide; Male; Mercaptoethanol; Mesna; Rats; Rats, Inbred Strains; Urinary Bladder Neoplasms