Effects of sodium thiosulfate in combination therapy of cis-dichlorodiammineplatinum and vindesine

Abstract

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.

Occupational exposure to antineoplastic agents and parameters for renal dysfunction

“…In patients treated with some antineoplastic agents, nephrotoxic side-effects are observed [2,3,6,8,9,12,14,15,19,30,32,33,35], The question is whether nephrotoxic effects occur in hospital workers who are occupationally ex posed to antineoplastic agents. Up to now, no such data have been published.…”

“…These parameters are widely used in occupational medicine for the detec tion of nephrotoxic effects in workers exposed to chem icals [16,35]. They are also applied clinically to control nephrotoxic side-effects of drugs such as aminoglyco sides [3] and antineoplastic agents like cisplatin [2,3,6,8,9,12,14,15,19,30,32,33,35].…”

Impact of Superselective Transarterial Infusion Therapy of High-Dose Cisplatin on Maxillary Cancer with Orbital Invasion

“…Sodium thiosulfate, which neutralizes cisplatin, enables us to administer massive cisplatin doses directly to feeding arteries of the tumor because it mitigates systemic side effects, such as myelosuppression and renal dysfunction. [19][20][21] Fortunately, none of the patients presented with leukopenia or renal dysfunction before treatment in this study, and we could safely use cisplatin in all subjects. We observed mild leukopenia in only 1 patient who received Taxotere combined with cisplatin.…”

Therapeutic efficacy of two‐route chemotherapy using cis‐diamminedichloroplatinum(II) and its antidote, sodium thiosulfate, combined with the angiotensin‐II‐induced hypertension method in a rat uterine tumor

“…We have reported the remarkable effectiveness of TRC against regionally confined tumors in laboratory animals (Taniguchi and Baba, 1982;Uozumi el al., 1983). Combination chemotherapy using DDP and STS has been safely and effectively used in the treatment of human cancers (Howell et al, 1983;Koba et al, 1983;Hirosawa et al, 1989).…”