mesna and Carcinoma--Transitional-Cell

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

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

Topics: Antineoplastic Agents; Brenner Tumor; Carcinoma, Transitional Cell; Female; Humans; Ifosfamide; Mesna; Middle Aged; Ovarian Neoplasms

Topics: Adenocarcinoma; Adenoma; Animals; Bacteria; Carcinoma, Transitional Cell; Cocarcinogenesis; Colon, Sigmoid; Colostomy; Feces; Female; Humans; Mesna; Nitrates; Nitrosamines; Oxidation-Reduction; Pentosan Sulfuric Polyester; Random Allocation; Rats; Rats, Wistar; Sigmoid Neoplasms; Ureter; Ureteral Neoplasms; Urinary Bladder; Urinary Diversion

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