抗癌剤膀胱内注入療法の基礎的,臨床的研究

Abstract

1) 1971～1979年末までに神戸大学医学部附属病院泌尿器科を受診した膀胱腫瘍患者のうち, 保存的手術後にMMC膀胱内注入療法をおこなった79症例と術後無治療32例の再発の有無を検討した.注入群の非再発率は1年75.9%, 5年63.6%である.術後無治療群の非再発率1年60.7%, 5年47.4%と比較すると注入群の非再発率が高かった.初発腫瘍と再発腫瘍を比較した場合は初発腫瘍に, 乳頭状と非乳頭状腫瘍を比較した場合は乳頭状腫瘍に, 単発性腫瘍と多発性腫瘍の場合は単発性腫瘍に, それぞれ予防効果が高く認められた.2)家兎膀胱粘膜の抗癌剤透過性に関する実験結果は, FT-207の透過率が良好で4時間値11.1%, ついでBLM 8.2%, MMC 2.7%であった.膀胱粘膜の透過性に変化を与えるとされる薬剤との併用実験では, Hyaluronidaseが抗癌剤の透過性を促進させうる薬剤であった.3) MMCとHyaluronidase併用による膀胱内注入療法は副作用も少なく, 膀胱腫瘍の術後再発予防として有用な治療法と考えられる

Intravesical instillation therapy of Mitomycin C (MMC) was attempted in 79 cases with the aim of prophylaxis against recurrence of bladder cancer after surgery. 20 ml saline solution containing 10 mg MMC was instilled into the bladder and retained for 2 hours once every week for a total of 10 instillation. The tumor free-rate of this treatment was 75. 9 % after I year, 69.5% after 2 years and 63.6% after 5 years, and the tumor-free rate of 32 cases without chemoprophylaxis was 60.7% after I year, 57% after 2 years and 47.4% after 5 years. The shape, multiplicity and pathological growth pattern of the cancer was clinically of "high risk" recurrence. On the basis of our observations, this prophylactic instillation therapy with MMC is concluded to be nseful for preventing the recurrence of bladder cancer after removal. Transport of anticancer agents (FT-207, BLM, MMC) through the rabbit's vesical mucosa and the effect of dimethylsulfoxide (DMSO), urokinase and hyaluronidase combined with anticancer to permeability were studied. The vesical mucosa was placed tightly between two syringes and transportion of anticancer material from one chamber to the other was investigated. In decreasing order, 11.1% of FT-207, 8.2% of BLM, and 2.7% of MMC, were transported within 4 hours. The permeability was not influenced by combination with urokinase or DMSO, but increased with hyaluronidase. The prevention of recurrence of bladder cancer was attempted in 13 cases by means of combined intravesical instillation of MMC and hyaluronidase. No recurrence was found for the postoperative 6~14 month period and slight miction pain was found in 2 out of 13 cases receiving the combined instillation therapy. I have concluded that this treatment is safe and useful for preventing the recurrence of bladder cancer.