mesna and Renal-Insufficiency

The purpose of this study was to make evidence-based recommendations regarding the mode, dosage and schedule of delivery of concomitant mesna (sodium-2-mercaptoethanesulfonate) to protect against ifosfamide-induced uroepithelial toxicity. A critical review of the literature from 1966 to 1996 was undertaken on mesna administration via the intravenous, oral, or combined modality routes. Outcome measures of urinary symptoms and macrohematuria were emphasized, since these endpoints of urotoxicity are most clinically relevant. The quality of evidence obtained from published clinical research was evaluated based on guidelines developed by the Canadian Task Force on the Periodic Health Examination. Recommendations are now made according to the strength of available evidence on the proper usage of mesna as a protective agent against ifosfamide-induced urotoxicity. There is good evidence that the use of mesna significantly reduces urinary symptoms of dysuria and frequency, as well as the incidences of macrohematuria and microhematuria, when administered concurrently with any dosage of ifosfamide regardless of tumor site. Mesna, given intravenously or orally, is superior to standard prophylaxis with vigorous hydration and alkalinization of urine. A commonly used schedule of intravenous mesna involves a dose equal to 60% of the total ifosfamide dose, divided into three aliquots and administered at 0 h, 4 h and 8 h after ifosfamide. Combined oral and intravenous mesna delivered in some tested schedules is equivalent to intravenous mesna alone, but the optimal schedule and dosage of combined formulation have not yet been established. There is fair indirect but no direct evidence that oral mesna alone is equivalent to intravenous mesna or combined modality use. Further research issues, such as patient compliance with oral mesna and other routes of mesna delivery, are discussed. Ongoing study in the appropriate use of mesna is needed to maximize its value as a uroprotective agent in the clinical setting.

Topics: Antineoplastic Agents, Alkylating; Drug Administration Schedule; Humans; Ifosfamide; Kidney; Mesna; Renal Insufficiency

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