Fundamental studies on intravesical instillation of cis-diamminedichloroplatinum for treatment of urinary bladder tumors. I: On the effects of intravesical instillation of cis-diamminedichloroplatinum in normal beagle dogs

DDPの膀胱内注入による局所・全身的毒性をBeagle犬および雑種成犬において検討した.1) DDPの膀胱内注入により血漿プラチナ濃度は3時間, 48時間の貯留では有意な上昇はみられなかった.注入前後の血液一般検査および血液化学検査においても, DDPの貯留内注入に起因すると考えられる変化は認められなかった.2) DDPの膀胱内注入によりイヌの膀胱組織内のプラチナ濃度は有意に上昇したが, 膀胱粘膜上皮および膀胱壁の肉眼的病理組織学的所見においては, 3時間の貯留では対照とした生理食塩水の貯留に比較して, その変化に差異は認められず, 48時間の貯留でもその対照群と比較して, やや粘膜浮腫や粘膜下出血が高度であったが, 潰瘍形成や粘膜の壊死・脱落は認められず, DDP膀胱内注入による局所の毒性はほとんどない.3) DDPの膀胱内注入による局所的および全身的毒性は低く, 膀胱腫瘍に対する直接抗腫瘍作用が確認されれば, DDPは膀胱内注入療法に有用な薬剤のひとつになりえる
Cis-Diamminedichloroplatinum (II) (DDP) is one of the most effective agents in the treatments of advanced bladder cancer, but little is known of its local and systemic toxicity when it is instilled intravesically. The objectives of this experiment were to study the local and systemic toxicity of intravesical DDP in order to know whether intravesical DDP is applicable for prophylaxis and/or definitive treatment of superficial bladder cancers. Six female Beagle dogs were used for the 48-hour retention study and 2 mongrel dogs were used for the 3-hour study. Plasma and bladder platinum concentration were measured following intravesical DDP, and also histopathological examination, urinalysis, complete blood count and blood chemistry were performed in order to know the toxicity of intravesical DDP. Plasma platinum concentration was not elevated significantly and no remarkable changes were observed in blood examinations after intravesical DDP. Bladder tissue platinum concentration was significantly elevated up to 16.96 micrograms/g . wet after 3 hours DDP retention and 4.02 +/- 2.8 micrograms/g . wet after 48 hours retention in dogs. At present, intravesical instillation of DDP seems to have minimum local toxicity and no systemic toxicity, but further study is necessary for long term topical instillation of DDP.