再発悪性神経膠腫へのbradykininを併用した化学療法の1臨床治験例

Clinical Trial of Bradykinin-enhancing Chemotherapy for a Recurrent Malignant Glioma : A Case Report

I．はじめに

　脳実質内に発生する悪性神経膠腫は，脳内に浸潤性に発育するため，手術で全摘出することは不可能である．初期治療として手術による腫瘍容積の減量，放射線治療，化学療法が行われており，初期治療は一定の腫瘍増殖抑制効果を示すが，ほとんどの症例で一定期間を経た後に再発・再増大（以下再発と称す）がみられ，再発からの生存期間は短く極めて予後不良である^7）．

　悪性神経膠腫再発時の治療は，ガンマナイフを含めた追加放射線治療や化学療法が行われているが，現時点では完全寛解や治癒せしめる方法はない．われわれは1990年代初頭より化学療法の効果を増強するために，血管透過性亢進物質を併用した化学療法の研究を進めてきた^{8-10,12-14）}．2001年2月に九州大学大学院医学研究院の倫理委員会での承認が得られ，bradykininを併用した化学療法の臨床治験を開始した．このたび第1例目の治療を行ったので，その経過および早期治療効果を報告する．

Patients with malignant glioma undergo a combined treatment with surgical resection, radiotherapy, andchemotherapy. Although those treatments usually show some restraining effects on the tumor, a relapseoccurs in most of the patients within a few years. We have investigated the feasibility and safety of intra-arterial chemotherapy for malignant brain tumors by enhancing vascular permeability using intra-arterialbradykinin infusion. In 2001, The Committee of Ethics in Kyushu University approved our clinical trial ofthe bradykinin-enhancing chemotherapy for recurrent malignant gliomas. We here report the first case ofour clinical trial. A 31-year-old man, who had undergone surgical resection followed by chemotherapy andirradiation for malignant progression of the left frontal astrocytoma over a period of 2 years, had a relapseof the tumor in the bilateral frontal lobes. After obtaining informed consent, bradykinin and carboplatinwere infused through a microcatheter at the left A 1 portion under general anesthesia. By dose escalation ofbradykinin, the enhanced lesion in the bilateral frontal lobes diminished on magnetic resonance imaging af-ter 3 trials with 3-week intervals, regardless of new lesions outside of the treated area. No neurological orphysiological complication including myelosuppression was noted.

Bradykinin-enhancing chemotherapy appeared to be effective and safe for malignant glioma. Because itwas able to increase drug delivery to the tumor, it was possible to reduce the size of the dose of chemo-therapeutic agent, which resulted in minimum complication.