Akimoto M, Nishihira T, Hirakawa H, Abe M, Ohuchi N, Mori S, Kumagai K
Second Department of Surgery, Tohoku University School of Medicine, Sendai, Japan.
Nihon Geka Gakkai Zasshi. 1991 Jan;92(1):64-74.
It has been generally agreed that the prognosis of widely spreaded "surgically unresectable" metastatic liver tumor originated from breast cancer is very poor. We reported here the result of clinical efficacy of sequential immunotherapy with intra-tumoral injection of large dose OK-432, after oral administration of cyclophosphamide during 7-10 days, and continuous perfusion of purified human recombinant interleukin-2 (rIL-2) from hepatic artery for the breast cancer patients with unresectable metastatic liver tumors. In all of 3 cases, metastatic liver tumor revealed overwhelming tumor reduction more than 50% of preoperative total tumor burden evaluated by computed tomography. Only 1 day after operation, large doses of OK-432 was injected intratumorally, both activity of Natural Killer (NK) cells and lymphokine activated killer (LAK) cells in peripheral blood lymphocytes were 5-20 folds augmented in all clinical trials. Serum tumor markers, i.e., Carcinoembryonic Antigen (CEA) and CA15-3, were rapidly decreased in all cases, respectively. Our clinical data indicate that intratumoral injection of large dose OK-432 and continuous administration of rIL-2 via hepatic artery, pretreated with cyclophosphamide, were clinically effective immunotherapy for reduction of metastatic liver tumor.
普遍认为，源自乳腺癌的广泛播散的“手术不可切除”转移性肝肿瘤预后很差。我们在此报告了对不可切除转移性肝肿瘤的乳腺癌患者进行序贯免疫治疗的临床疗效结果，该治疗方法为在7至10天内口服环磷酰胺后，瘤内注射大剂量OK-432，并经肝动脉持续灌注纯化的人重组白细胞介素-2（rIL-2）。在所有3例患者中，通过计算机断层扫描评估，转移性肝肿瘤显示肿瘤负荷大幅降低，超过术前总肿瘤负荷的50%。术后仅1天，就在瘤内注射大剂量OK-432，在所有临床试验中，外周血淋巴细胞中的自然杀伤（NK）细胞和淋巴因子激活杀伤（LAK）细胞活性均增强了5至20倍。所有病例的血清肿瘤标志物，即癌胚抗原（CEA）和CA15-3，均分别迅速下降。我们的临床数据表明，瘤内注射大剂量OK-432以及经环磷酰胺预处理后经肝动脉持续给予rIL-2，是减少转移性肝肿瘤的有效临床免疫疗法。
