腎癌に対するα型インターフェロンの抗腫瘍効果検討 病理剖検例を中心に

Abstract

腎癌に対してα-Interferon (γ-IFN-αA)の抗腫瘍効果を組織学的に検討した.1)対象症例は14例で, 腎摘除後の転移症例10例, 原発巣に対する塞栓術だけをおこなった症例2例, 手術をおこなわないもの1例, IFN治療中に腎摘除術をおこなったもの1例であった.投与法は筋注連日投与とし, 300万単位から始めて5, 000万単位を上限として, 3日ごとに増量のうえ最大耐用量で維持した.組織学的検討は, 剖検後13例, 治療中のもの1例におこなった.2) 14例での効果判定は, 小山・斎藤班の基準で, PR 2例, MR 1例, NC 5例, PD 6例(局所投与1例において, 局所的にはPR)であった.3)組織学的抗腫瘍効果では, 原発巣の細胞組織型で, clear cell 8例, clear cellおよびgranular cellの混合型3例, clear cellおよびsarcomatoid type 1例, papillary type 1例で, 1例を除いて悪性度分類はGrade 3であり, これらと転移部位の組織像と比較検討した.臨床的に有効であったものは組織学的にも有効であり, また, 残存転移巣において, 臨床的に有効無効にかゝわらず, 原発巣で認めたGrade 3の細胞型は認めず, よりGradeの低いものか, sarcomatoid typeのよりGradeの高いものが残っていた.4)組織学的にリンパ球などの細胞浸潤像を認めず, 免疫学的反応をうかがわせる所見はえられなかった.5)副作用は, 発熱, 食思不振, 全身倦怠感をほぼ全例に認め, 白血球減少症, 血小板減少症などの骨髄抑制も認めた.肝機能障害もかなりの例に認め, 中枢神経系障害はひとつのdose limiting factorであった

The anti-tumor activity of alpha-interferon (gamma-IFN-alpha A) was assessed histopathologically in 14 patients with metastasized renal cell carcinoma. Ten of the patients had undergone radical nephrectomy, two patients embolization alone, one patient no prior treatment and one patient nephrectomy in IFN therapy. IFN was given daily intramuscularly starting at the dose of 3 X 10(6) U and increased every 3 days to the maximum of 5 X 10(7) U. This treatment could be tolerated. The clinical response was evaluated according to the criteria of Koyama and Saitou. Two of the patients showed partial response, one patient minor response, five patients no change and six patients progressive disease. The clinical responders also had histopathologically detected improvement. Renal cell carcinoma of a higher grade (sarcomatoid type) or lower grade (grade II greater than or equal to), was seen frequently, and the papillary or tubular type was resistant to IFN. The clear cell type and grade III tumor was more responsive to IFN. Histopathologically, no lymphocyte infiltration into the cancer cell focus was seen and the immunologic reaction was not considered to be affected by IFN, because of the myelosuppression due to the IFN therapy and because more responders used the steroid hormone like predonizolone to prevent side effects. Fever, anorexia and general malaise were observed in all cases. Myelosuppression like leukocytopenia and/or thrombocytopenia was also observed but easily improved after cessation of IFN medication or decrease of IFN dose. Liver dysfunction was observed but spontaneous recovery without discontinuation of IFN therapy or decrease of IFN dose was seen in two cases. The disturbance of the central nervous system similar to the occurrence of abnormal EEG waves or psychosis, was a dose-limiting factor. Further studies especially to develop an appropriate method of administration and the combination with other anti-cancer agents must be studied.