Efficacy of two-route chemotherapy using cis-diamminedichloroplatinum(II) and its antidote, sodium thiosulfate, in combination with angiotensin II for rat liver tumor.
To improve the therapeutic effects of conventional TRC using i.a. CDDP plus simultaneous i.v. STS in a rat liver tumor, we made use of the AT-II-induced hypertension method, in combination with TRC. The decrease in tumor area (-15%), measured 8 days after the TRC using CDDP 12 mg/kg i.a. plus i.v. post-administration (5 min later) of STS 1,264 mg/kg, was much greater than that (+ 13%) seen in the conventional TRC, but BUN level was elevated (44.9 mg/dl). AT-II (15 micrograms/kg) administered i.a. simultaneously with CDDP normalized the BUN level (20.3 mg/dl) and further decreased (-15% to -31%) the tumor area (modified TRC). The modified TRC also exhibited a higher anti-tumor effect than did CDDP 3 mg/kg with AT-II i.a. (5%) at a similar BUN level (22.2 mg/dl). Loss of body weight, decrease in WBC count and changes in serum transaminases of rats treated with the modified TRC were tolerable. The improved therapeutic effect of the modified TRC was explained as follows: during AT-II-induced hypertension, (I) CDDP delivery to the tumor was increased by 150% and (2) CDDP delivery to the kidney was decreased by 35%. The latter effect of AT-II made feasible the post-administration of STS to CDDP.
Department of Experimental Cell Research, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan.
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K
Hasuda
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Kobayashi
K
K
Aoki
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S
Taniguchi
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T
Baba
D000804:Angiotensin II / Q000008:administration & dosage*; D000818:Animals; D000931:Antidotes / Q000008:administration & dosage*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D002945:Cisplatin / Q000008:administration & dosage*; D005260:Female; D008114:Liver Neoplasms, Experimental / Q000188:drug therapy*; D010984:Platinum / Q000032:analysis; D051381:Rats; D011919:Rats, Inbred Strains; D013885:Thiosulfates / Q000008:administration & dosage*
D000931:Antidotes; D013885:Thiosulfates; D000804:Angiotensin II; D010984:Platinum; C017717:sodium thiosulfate; D002945:Cisplatin