Effects of a combination chemotherapy using cis-diamminedichloroplatinum (II) (DDP) and its antidote, sodium thiosulfate (STS), on metastatic lung tumour in rats were studied.
Rats were given an upper hemibody infusion (UHI) of 15 mg/kg DDP immediately after occlusion of the abdominal aorta and i.v. administration of 1581 mg/kg STS (200-fold molar ratio to DDP) 10 min later. The aortic clamp was released at approximately 11 min after the beginning of UHI when a half volume of STS solution was infused. Antitumour and side effects in this group were compared with those in the respective control groups given 5 mg/kg DDP alone by UHI or by systemic administration.
In the group given UHI of DDP (DDP-UHI) in combination with STS, there was a significantly better antitumour effect than seen in the group given DDP alone, as evaluated by the number of lung tumour nodules and survival time after inoculation of the transitional cell carcinoma into the lung. Nephrotoxicity, as assessed by increase in BUN levels, was completely avoided. Haematological toxicity effects assessed by decreases in WBC were slight but body-weight loss due to anorexia was severe.
Similar content being viewed by others
References
Baba, T., and Nishikawa, K., 1980, Effective combination of anticancer drug with its antidote for chemotherapy of hepatic metastasis.Gann,71, 157–158.
Fawcett, J. K., and Scott, J. E., 1960, A rapid and precise method for the determination of urea.Journal of Clinical Pathology,13, 156–159.
Guyton, A. C., 1981,Textbook of Medical Physiology (Philadelphia: W. B. Saunders Company), pp. 408–409.
Hellekant, C., and Svanberg, L., 1978, Bronchial artery infusion of Nlitomycin-C in advanced bronchogenic carcinoma.Acta radiologica,17, 449–462.
Howell, S. B., and Taetle, R., 1980, Effect of sodium thiosulfate oncis-diamminedichloroplatinum (II) toxicity and antitumour activity in L1210 leukemia.Cancer Treatment Reports,64, 611–616.
Inokuchi, K., Nakamura, T., Ienaga, S., Akiyoshi, T., and Ikeda, T., 1965, Intraoperative use of Mitomycin-C with spleen and bone marrow shielding technique in gastric cancer surgery.Gan no Rinsho,11, 142–150.
Ishizawa, M., Taniguchi, S., and Baba, T., 1981, Protection by sodium thiosulfate and thiourea against lethal toxicity ofcis-diamminedichloroplatinum (II) in bacteria and mice.Japanese Journal of Pharmacology,31, 883–889.
Iwamoto, Y., Kawano, T., Uozumi, J., Aoki, K., and Baba, T., 1984, “Two-route chemotherapy” using high-dose i.p. cisplatin and i.v. sodium thiosulfate, its antidote, for peritoneally disseminated cancer in mice.Cancer Treatment Reports (in the press).
Litterst, C. L., Gram, T. E., Debrick, R. L., Leroy, A. F., and Guarino, A. M., 1976, Distribution and disposition of platinum following intravenous administration ofcis-diamminedichloroplatinum (II) (NSC 119875) to dogs.Cancer Research,36, 2340–2344.
Madias, N. E., and Harrington, J. T., 1978, Platinum nephrotoxicity.American Journal of Medicine,65, 307–314.
Newman, E. V., Gilman, A., and Philips, F. S., 1946, The renal clearance of thiosulfate in man.Bulletin of Johns Hopkins Hospital,79, 229–242.
Nicholas, P. S., and Brian, B., 1960, Selective chemotherapy of the lung during unilateral pulmonary arterial occlusion with a balloon-tipped catheter. Journal of Thoracic and Cardiovascular Surgery, 40, 653–666.
Rheinlander, H. F., Miller, H. H., Moquin, R. B., and Deterling, JR, R. A., 1962, Upper hemibody infusion with alkylating agents for advanced lung cancer. Journal of Thoracic and Cardiovascular Surgery,44, 801–810.
Sagiyama, K., Uozumi, J., Aoki, K., and Baba, T., 1983, Effecacy of “two-route chemotherapy” using intra-arterial cisplatin and iv sodium thiosulfate, its antidote, in rat bladder tumour.Cancer Treatment Reports,67, 567–572.
Soderberg, JR, C. H., Colbert, M. P., and Leone, L. A., 1964, Bronchial artery infusion therapy of lung neoplasms with nitrogen mustard.Surgery,56, 897–904.
Suzuki, M., Hori, K., Abe, I., Saito, S., and Sato, H., 1981, A new approach to cancer chemotherapy: selective enhancement of tumour blood flow with angiotensin II.Journal of the National Cancer Institute,67, 663–669.
Taniguchi, S., and Baba, T., 1982, “Two-route chemotherapy” usingcis-diamminedichloroplatinum (11) and its antidote, sodium thiosulfate, for peritoneally disseminated cancer in rats.Gann,73, 475–479.
Uozumi, J., Sagiyama, K., Aoki, K., Iwamoto, Y., and Baba, T., 1983, Effectiveness of “two-route chemotherapy” using cisplatin and its antidote, sodium thiosulfate, on life span of rats bearing metastatic liver tumours,Cancer Treatment Reports,67, 1067–1074.
Von HOFF, D. D., Schilsky, R., Reichart, C. M., Reddick, R. L., Rozencweig, M., Young, R. C., and Muggia, F. M., 1979, Toxic effects of cis-dichlorodiammineplatinum (II) in man.Cancer Treatment Reports,63, 1527–1531.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Iwamoto, Y., Aoki, K., Kawano, T. et al. Upper hemibody infusion ofcis-diamminedichloroplatinum (II) followed by systemic antidote, sodium thiosulfate, for lung metastasis in rats. Clin Exp Metast 2, 261–270 (1984). https://doi.org/10.1007/BF00132933
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00132933