Premium
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
Author(s) -
Kobayashi Hiroaki,
Hasuda Keitaro,
Taniguchi Shun'Ichiro,
Baba Tsuneo
Publication year - 1991
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.2910470618
Subject(s) - nephrotoxicity , sodium thiosulfate , medicine , uterus , chemotherapy , urology , abdominal aorta , kidney , pharmacology , angiotensin ii , cisplatin , aorta , endocrinology , blood pressure , chemistry , inorganic chemistry
To enhance the therapeutic effect of conventional TRC using intra‐arterial (i.a.) DDP plus simultaneous i.v. STS, we combined the AT‐II‐induced hypertension method with TRC and evaluated its efficacy for a rat uterine tumor, using the simulation of intra‐arterial chemotherapy for human uterine tumors. During interruption of arterial blood flow by vascular manipulations, DDP plus AT‐II were injected for 10 min through the abdominal aorta in the direction of the uterus. Then STS was administered i.v. for a further 5 min and all the arterial restrictions were released. This modified TRC using AT‐II showed a much higher anti‐tumor effect than that seen in conventional TRC without AT‐II and was free from DDP‐induced renal damage. On the other hand, severe nephrotoxicity was unavoidable in the rats given the delayed i.v. administration of STS to i.a. DDP alone. The feasibility of post‐administration of STS without obvious nephrotoxicity in modified TRC was explained by transient inhibition of DDP delivery to the kidney during the AT‐II‐induced hypertension. The loss of body weight and the decrease in the number of leukocytes after this therapy were tolerable. Modified TRC showed a higher anti‐tumor effect and a lower nephrotoxicity compared with other treatments, as follows: DDP i.a. with or without AT‐II; i.v. infusion of DDP alone. Such a superior anti‐tumor effect of modified TRC consists of the following 2 factors: (i) the post‐administration of STS leading to the delayed neutralization of DDP at the tumor site; (ii) the selective enhancement of DDP delivery to the tumor tissue during AT‐II‐induced hypertension.