Effects of sodium thiosulfate in combination therapy of cis-dichlorodiammineplatinum and vindesine.
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.
Hirosawa
A
A
Department of Clinical Pathology, Nippon Medical School, Tokyo, Japan.
Niitani
H
H
Hayashibara
K
K
Tsuboi
E
E
D000230:Adenocarcinoma / Q000188:drug therapy / Q000503:physiopathology; D000931:Antidotes / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000503:physiopathology; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000503:physiopathology; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D002986:Clinical Trials as Topic; D006801:Humans; D007668:Kidney / Q000187:drug effects / Q000503:physiopathology; D008175:Lung Neoplasms / Q000188:drug therapy / Q000503:physiopathology; D010984:Platinum / Q000032:analysis; D011897:Random Allocation; D013885:Thiosulfates / Q000627:therapeutic use*; D013997:Time Factors; D014751:Vindesine / Q000008:administration & dosage / Q000009:adverse effects
D000931:Antidotes; D013885:Thiosulfates; D010984:Platinum; C017717:sodium thiosulfate; D002945:Cisplatin; D014751:Vindesine