Renal dysfunction and urinary disorders are the most troublesome adverse reaction to
anticancer agents such as
cisplatin (CDDP) and
ifosfamide (IFM). A number of antidotes such as
sodium thiosulfate (STS),
WR-2721,
thiourea,
diethyldithiocarbamate and
bismuth subnitrate have been tested to reduce the nephrotoxicity of CDDP. One notable method previously reported by Baba et al. and Pfeifle et al involves the i.v. administration of STS to prevent the nephrotoxicity of CDDP given locally. Since STS has been proven clinically effective in reducing such side effects, we initiated a study of STS in patients with advanced
non-small-cell lung carcinoma who were given a combination of CDDP and
vindesine (VDS) systemically. Urinary levels of
beta 2-microglobulin (BMG) and
N-acetyl-beta-D-glucosaminidase (NAG) were measured as an index of proximal tubular function. Analysis of both levels indicated that STS suppressed CDDP nephrotoxicity to a minimal level. Therefore, the present study clearly demonstrates that systemic administration of STS reduces the side effects of CDDP to a minimal level without impairing its antitumor activity and that STS treatment is applicable in a repeated
chemotherapy using CDDP alone or in combination with other
antitumor agents. Furthermore, it has been reported that
urinastatin and
fosfomycin may exert potent effects to reduce untoward nephrotoxicity of CDDP. IFM causes urinary disorders such as
hematuria, reducing its clinical usefulness,
Sodium 2-mercaptoethane sulfonate (
mesna) is the
thiol compound which binds specifically to the urinary toxic metabolites of IFM, and thereby decreases the undesirable effect of IFM on the lower urinary tract, especially on the bladder. Recently, it was reported by a Osaka
mesna study group that
mesna is useful for the prevention of IMF-induced urinary disorders. It was considered that above new treatments were required in repeating
chemotherapy which induced urogenital toxicity.