Intravesical therapy of pirarubicin (THP) against bladder cancer: Penetration of THP into bladder cancer tissue and its prophylactic effect against intravesical recurrence of bladder cancer after transurethral resection

• Published in: Japanese Journal of Chemotherapy Vol. 50; no. 4; pp. 227 - 231
• Main Authors: Hayashi Norihiro, Wada Teturo, Abe Kazuhiro, Hatano Takashi, Kiyota Hiroshi, Oishi Yukihiko
• Format: Journal Article
• Language: Japanese
• Published: Japanese Society of Chemotherapy 2002; 公益社団法人 日本化学療法学会
• Subjects: intravesical therapy; pirarubicin; prophylaxis; superficial bladder cancer
• ISSN: 1340-7007; 1884-5886
• DOI: 10.11250/chemotherapy1995.50.227

We studied the penetration of pirarubicin (THP) into bladder cancer tissue and its prophylactic effect in 5-day intravesical administration against intravesical recurrence of bladder cancer after transurethral resection (TUR-BT), to clarify its effectiveness and safty.(1) Penetration of THP into bladder cancer tissue after intravesical administration: Subjects were 32 patients with superficial bladder cancer. THP (30mg) was administered transurethrally 1 hour before TUR in 26 patients and 24 hours before in 6. Bladder cancer tissue and normal bladder mucosa were obtained from each patient by TUR. THP concentrations in bladder cancer tissue and normal bladder mucosa were measured by HPLC and compared. THP concentrations in bladder cancer tissue were significantly higher than in normal mucosa, when THP was administered 1 hour before TUR, but no significant difference was seen in THP concentrations between bladder cancer tissue and normal mucosa when THP was administered 24 hours before TUR.(2) Prophylactic effect of intravesical administration of THP against intravesical recurrence of bladder cancer after TUR-BT: Subjects were 24 patients with superficial bladder cancer. After TUR-BT, THP (30mg) was administered transurethrally for 5 days. Mean follow-up was 8.8 months (2 to 26 months). Seven of 24 had intravesical recurrence 2 to 8 months postoperatively, so the short-term prophylactic effect was 70.8%. Adverse effects occurred in 11 (45.8%), mostly low-grade vesical irritability without stopping intravesical THP therapy. No general adverse effect such as leukocytepenia and heart damage were seen.These results indicate that 5-day intravesical THP therapy is safe and effective for prophylaxis against intravesical recurrence of superficial bladder cancer after TUR-BT. 表在性膀胱癌の経尿道的切除術 (transurethral resection of bladder tumor; TUR-BT) 後の膀胱腔内再発予防のためのpirarubicin (以下THP) 連続膀胱内注人療法の有用性と安全性を明らかにする目的で, THP注入後の腫瘍組織内濃度を測定するとともに, THP膀胱内注入療法の再発予防効果と副作用の有無について検討した。(1) THP組織内濃度の検討: 1992年3月から1995年2月までに東京慈恵会医科大学にて表在性移行上上皮癌と診断された初発膀胱癌症例32例を対象とした。対象症例をTHP 30mg/body膀胱内注人1時間後 (26例) と24時間後 (6例) の2群に分け, それぞれ正常膀胱粘膜組織と腫瘍組織におけるTHP組織内濃度をHPLC法により測定した。1時間後の腫瘍組織内THP濃度は, 正常膀胱粘膜組織のそれらに比べ有意に高値であったが, 24時間後では腫瘍, 正常膀胱粘膜組織ともに測定感度以下の値であった。(2) 5日間連続THP膀胱内注入療法の表在性膀胱癌術後再発予防効果: 1998年7月から1999年8月までに富士市立中央病院においてTUR-BT施行後, 表在性移行上皮癌と診断された24例を対象とし, THP 30mg/body 5日間連続膀胱内注入療法を施行した。平均観察期間は8.8か月 (範囲: 2～26か月) で, 24例中7例に術後2～8か月に再発が認められ, 近接効果としての非再発率は7008%であった。副作用は, 45.8%(11/24例) に膀胱刺激症状が認められたが, これによって投与を中1土した症例は認められなかった。5日間連続THP膀胱内注入療法後の血中THP濃度は測定限界値以下であり, 全身的副作用はなかった。以上より5日間連続THP膀胱内注入療法は安全で, しかも表在性膀胱癌術後に優れた再発予防効果があるものと考えられた。