Placebo-controlled double-blind comparative study on the preventive efficacy of mesna against ifosfamide-induced urinary disorders

Abstract

In order to evaluate the preventive efficacy, safety and usefulness of mesna (Sodium 2-mercaptoethane sulfonate) against ifosfamide-induced urinary disorders, a placebo-controlled double-blind comparative study was performed. Ifosfamide was administered by intravenous drip infusion at a daily dose of 2 g/m2 for 5 consecutive days, and mesna was intravenously administered at 20% of the ifosfamide dose, three times daily for 5 consecutive days. The results obtained are as follows. (a) Of 101 accrued patients, 91 patients were evaluated consisting of 45 for the mesna group and 46 for the placebo group. There was no intergroup difference in the number of the evaluated cases and patient characteristics. (b) Micturition pain and feeling of residual urine graded as moderate or severe were not observed for the mesna group, but were observed for the placebo group with incidences of 19.6% (9/46) for micturition pain and 15.2% (7/46) for feeling of residual urine; the intergroup differences in the appearance of these urinary symptoms were statistically significant (P = 0.0003 for micturition pain; P = 0.0009 for feeling of residual urine). The incidence of hematuria graded as moderate or severe was 6.7% (3/45) in the mesna group, which was significantly lower than the 32.6% (15/46) in the placebo group (P = 0.0008). (c) No side-effect attributable to mesna was observed. (d) A judgment of "useful" was obtained in 80.0% (36/45) of the patients treated with mesna, which was significantly higher than the 34.8% (16/46) of the patients treated with placebo (P = near 0). On the basis of the above results, we conclude that the preventive efficacy, safety and usefulness of mesna against ifosfamide-induced urinary disorders have been well demonstrated in this study.

Use of mesna to prevent ifosfamide-induced urotoxicity

“…In the clinical setting, the possible interaction of mesna with the antiproliferative action of ifosfamide can be assessed by studying ifosfamide-induced myelosuppression with and without mesna. Fukuoka et al [60] demonstrated similar hematological toxicities from ifosfamide whether it was given with mesna or with placebo. Furthermore, no significant difference in tumor response was observed (Pp0.7898).…”

“…Phase III trials of intravenous mesna versus placebo/no treatment There are at least three randomized studies in the literature comparing the preventive efficacy of mesna and/ of placebo/no treatment for ifosfamide-induced urotoxicity [60][61][62]. The best evidence comes from a placebocontrolled, double-blind study by Fukuoka et al [60], in which 101 patients with advanced primary or secondary lung cancer being treated by single-agent ifosfamide therapy were randomly assigned to mesna or placebo.…”

“…The best evidence comes from a placebocontrolled, double-blind study by Fukuoka et al [60], in which 101 patients with advanced primary or secondary lung cancer being treated by single-agent ifosfamide therapy were randomly assigned to mesna or placebo. Of the 101 patients enrolled in the study, 91 were available for data analysis, 10 were excluded because of poor performance status, pre-existent hematuria, and/ or ifosfamide discontinuation due to non-urinary related side effects.…”

Reactive Carbonyl Species Scavengers—Novel Therapeutic Approaches for Chronic Diseases

“…An initial trial in 1986 showed that co-administration of MESNA with ifosfamide to patients with advanced non-small cell lung cancer significantly reduced ifosfamide-induced hemorrhagic cystitis [72]. A subsequent placebo-controlled, double-blind study showed that co-administration of MESNA with ifosfamide markedly reduced micturition pain and hematuria compared to placebo [73]. MESNA administration to patients receiving cyclophosphamide prior to bone marrow transplant also reduced overall rates of hematuria, discomfort and bladder spasms, and urinary tract infections [74].…”

U.S. Food and Drug Administration Drug Approval Summaries: Imatinib Mesylate, Mesna Tablets, and Zoledronic Acid

“…Mesnex ® (Baxter Healthcare Corporation) is indicated as a prophylactic agent to reduce the incidence of ifosfamide-394 FDA Approval of Imatinib, Mesna, and Zoledronic Acid Food and Drug Administration (FDA) approved mesna tablets as a prophylactic agent to reduce the incidence of ifosfamideinduced hemorrhagic cystitis [15][16][17][18]. Mesna for i.v.…”