Oka M, Hazama S, Yoshino S, Shimoda K, Suzuki M, Shimizu R, Yano K, Nishida M, Suzuki T
Second Department of Surgery, Yamaguchi University School of Medicine, Japan.
Cancer Immunol Immunother. 1994 Mar;38(3):194-200. doi: 10.1007/BF01525641.
An important objective for patients with unresectable hepatocellular carcinoma (HCC) is the development of effective chemotherapy. We administered a combination of biological response modifiers and anticancer agents to 24 patients with unresectable HCC. Each case had an implanted infuser port which was connected to a catheter placed in the hepatic artery for the intraarterial (i.a.) administration of chemotherapy. The following agents were administered to each patient: recombinant interleukin-2 (800,000 JRU/day infused i.a. continuously for 6 days/week); OK-432 (5 KE injected i.a. twice in 4 weeks and i.m. three times per week); Adriamycin (10 mg injected i.a. twice in 4 weeks); cyclophosphamide (300 mg injected i.a. twice in 4 weeks), and famotidine (40 mg/day administered orally). Objective response was assessed according to tumor size measured by computed tomography and angiography before and after treatment. We observed a complete response (CR) in 4, partial response (PR) in 3, minor response (MR) in 7, no change (NC) in 7, and progressive disease (PD) in 3. The response rate (CR+PR+MR) was 58.3%. The overall 2-year survival rate was 52%. The 2-year survival rate of the responders (CR+PR+MR) was 80%, while that of the non-responders (NC+PD) was 0%. There was a significant difference between the responders and non-responders in respect to survival rate (P < 0.05). The percentages of CD25+ cells, CD56+ cells, and Leu7-CD16+ cells and NK activity in the peripheral blood showed a significant increase following the regimen. Serum levels of tumor necrosis factor alpha TNF alpha rose after the initiation of OK-432. TNF alpha levels were higher in the responders than in the non-responders. Adverse effects included high fever (all patients) and severe transient hypotension (15 patients) that was controlled by conservative therapy. Combined immunochemotherapy administered intraarterially may be a new strategy for treating unresectable HCC.
对于无法切除的肝细胞癌（HCC）患者而言，一个重要目标是开发有效的化疗方法。我们对24例无法切除的HCC患者给予了生物反应调节剂和抗癌药物的联合治疗。每例患者均植入了输液港，该输液港与置于肝动脉的导管相连，用于动脉内（i.a.）化疗给药。每位患者接受了以下药物治疗：重组白细胞介素-2（800,000 JRU/天，每周连续6天经动脉内持续输注）；溶链菌制剂（5 KE，4周内动脉内注射2次，每周肌肉注射3次）；阿霉素（10 mg，4周内动脉内注射2次）；环磷酰胺（300 mg，4周内动脉内注射2次），以及法莫替丁（40 mg/天，口服给药）。根据治疗前后通过计算机断层扫描和血管造影测量的肿瘤大小评估客观缓解情况。我们观察到4例完全缓解（CR）、3例部分缓解（PR）、7例轻度缓解（MR）、7例病情无变化（NC）以及3例疾病进展（PD）。缓解率（CR+PR+MR）为58.3%。总体2年生存率为52%。缓解者（CR+PR+MR）的2年生存率为80%，而未缓解者（NC+PD）的2年生存率为0%。缓解者和未缓解者在生存率方面存在显著差异（P<0.05）。外周血中CD25+细胞、CD56+细胞以及Leu7-CD16+细胞的百分比和NK活性在治疗方案实施后显著升高。在开始使用溶链菌制剂后，血清肿瘤坏死因子α（TNFα）水平升高。缓解者的TNFα水平高于未缓解者。不良反应包括高热（所有患者）和严重的短暂性低血压（15例患者），后者通过保守治疗得到控制。经动脉内给予联合免疫化疗可能是治疗无法切除的HCC的一种新策略。
