The effects of
sodium thiosulfate (STS) were studied in patients who received a combination
therapy of cis-
dichlorodiammineplatinum (CDDP) and
vindesine. In this study, 61 patients with
non-small-cell lung carcinoma were randomized to receive either CDDP and
vindesine (both given i.v.) with i.v. STS [30 patients, STS(+) group] or CDDP and
vindesine without STS [31 patients, STS(-) group]. In the STS(+) group, 16 patients who showed an improvement (reduction in
tumor size or relief of symptoms) after the first course received the second STS(+) treatment, and 15 patients in the STS(-) group who showed an improvement after the first course received the second STS(-) treatment. 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. Serum BMG, blood
urea nitrogen (BUN), and total as well as 24-h
creatinine clearance levels were measured as an index of glomerular function. There were no significant differences in these levels between the STS(+) and STS(-) groups. The urinary recoveries of total
platinum 24 h after CDDP administration were 29% and 21% in the STS(+) and STS(-) groups, respectively. The mean plasma concentrations of total
platinum at 24 h after CDDP administration were 2.24 and 2.70 micrograms/ml in the STS(+) and STS(-) groups, respectively. There were no significant differences in the response rates of the STS(+) and STS(-) groups at a fixed dose of 100 mg/m2 CDDP. 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.