腎癌脳転移に対するinterferon—γ皮下投与の治療効果を薬物動態から検討した1例

Pharmacokinetics of Intratumoral Interferon-γ Activity Following Subcutaneous Administration of Recombinant Interferon-γ in a Patient with Metastatic Brain Tumor Derived from Renal Cancer

Ι．はじめに

　腎癌の転移性脳腫瘍の予後は肺癌のそれと比べ比較的良好であるが，放射線療法や化学療法に抵抗性であるため，その治療法は確立されていない^3,9）．近年，腎癌に対する治療法のひとつとして，遺伝子組換え型インターフェロン（IFN）を用いた免疫療法が行われている．腎癌の脳転移に対してもIFN療法が試みられているが，その有効例は少ない^4,5,10,15）．

　最近，われわれは腎癌の脳転移に対しIFN—γの皮下投与が奏功した症例を経験した．現在までIFN—γ皮下投与が腎癌の脳転移に抗腫瘍効果を示した報告は見あたらない．IFN—γ療法の治療効果を解析するために，腫瘍摘出腔内に留置したOmmaya reservoirから採取した貯留液中のIFN—γ濃度を血中濃度と共に経時的に測定し，その薬物動態を検討したので報告する．

Pharmacokinetic studies of intratumoral interferon (IFN) -γ activity were performed 1 week and 1 month after subcutaneous (s. c.) administration of recombinant IFN-γ (specific activity=1×10⁷units/mg protein) to a patient with metastatic brain tumor in the right occipit-al lobe derived from primary renal cancer. The patient, a 59-γear-old man, underwent total removal of the le-sion on April 10, 1991, with placement of an indwelling Ommaya Reservoir in the tumor cavity. The histologic-al diagnosis was clear-cell carcinoma. His postoperative course was uneventful. Due to detection of a new ring-like enhancing mass in the right temporal lobe on serial CT examination on May 27, radiotherapy was discon-tinued immediately after delivery of a total dose of 3OGy. Recombinant IFN-γ was then admistered s. c. at a dose of 3×10⁶units/day for 6 weeks, and induced a partial response. During IFN-γ therapy, IFN-γ activity in intratumoral fluid was measured 0 min, 30 min, 90 min and 6 hours after s.c. injection of IFN-γ. The level of IFN activity was determined by an enzyme-linked immunosorbent assay. Intra-tumoral IFN-γ activity gra-dually increased, and showed the highest of measured values at 6 hours after administration, while serum IFN activity decreased rapidly with a half-life of 30 min. The patient was discharged on July 30, but died from complications of aspiration pneumonia on September 2, 1991.