van Herpen C M, Jansen R L, Kruit W H, Hoekman K, Groenewegen G, Osanto S, De Mulder P H
Department of Medical Oncology, University Hospital Nijmegen, The Netherlands.
Br J Cancer. 2000 Feb;82(4):772-6. doi: 10.1054/bjoc.1999.0997.
In patients with metastatic renal cell carcinoma response rates of 7-26% have been achieved with immunotherapy. A high response rate of 48% in 35 patients has been reported for treatment with the combination of interferon-alpha (IFN-alpha), interleukin-2 (IL-2) and 5-fluorouracil (5-FU) (Atzpodien et al (1993a) Eur J Cancer29A: S6-8). We conducted a multicentre phase II study to confirm these results. Metastatic renal cell carcinoma patients were treated as outpatients with an 8-week treatment cycle. Recombinant human IL-2 20 MU m(-2) was administered subcutaneously (s.c.) three times a week (t.i.w) in weeks 1 and 4 and 5 MU m(-2) t.i.w. in weeks 2 and 3. Recombinant human IFN-alpha 2a 6 MU m(-2) was administered s.c. once in weeks 1 and 4 and t.i.w. in weeks 2 and 3, and 9 MU m(-2) t.i.w. in weeks 5-8. 5-FU (750 mg m(-2)) was given as a bolus injection intravenous once a week in weeks 5-8. The treatment cycle was repeated once in case of response or minor response. Fifty-two patients entered the study. All had undergone a nephrectomy and had progressive metastatic disease. The median WHO-performance status was 1, the median number of metastatic sites was 2 (range 1-5) and the median time between the diagnosis of the primary tumour and the start of treatment was 12.9 months (range 1-153). Among the 51 patients, including four patients with early progressive disease, who were evaluable for response, the response rate was 11.8% (95% confidence interval (CI) 2.9-20.7%), with no complete responses. Median duration of response was 8.3 (range 3.8-22.4+) months. Median survival was 16.5 (range 1.8-30.5+) months. Grade 3/4 toxicity (WHO) occurred in 29/52 (55.8%) of the patients in cycle 1 and in 6/16 (37.5%) of the patients in cycle 2. It consisted mainly of anorexia, fatigue, nausea, fever and leucocytopenia. We cannot confirm the high response rate in patients with metastatic renal cell carcinoma treated with the combination of IFN-alpha, IL-2 and 5-FU, as described by Atzpodien et al.
在转移性肾细胞癌患者中，免疫疗法的缓解率为7%-26%。据报道，用α-干扰素（IFN-α）、白细胞介素-2（IL-2）和5-氟尿嘧啶（5-FU）联合治疗35例患者，缓解率高达48%（阿茨波迪恩等人（1993年a）《欧洲癌症杂志》29A：S6-8）。我们进行了一项多中心II期研究以证实这些结果。转移性肾细胞癌患者作为门诊病人接受为期8周的治疗周期。重组人IL-2 20 MU m(-2)于第1周和第4周每周皮下注射（s.c.）3次（每周3次），第2周和第3周为5 MU m(-2)每周3次。重组人IFN-α 2a 6 MU m(-2)于第1周和第4周皮下注射1次，第2周和第3周每周3次，第5-8周为9 MU m(-2)每周3次。5-FU（750 mg m(-2)）于第5-8周每周静脉推注1次。若出现缓解或轻微缓解，则重复治疗周期1次。52例患者进入研究。所有患者均已接受肾切除术且有进行性转移性疾病。世界卫生组织（WHO）的中位体能状态为1，转移部位的中位数量为2（范围1-5），原发性肿瘤诊断与开始治疗之间的中位时间为12.9个月（范围1-153）。在51例可评估缓解情况的患者中，包括4例早期疾病进展患者，缓解率为11.8%（95%置信区间（CI）2.9-20.7%），无完全缓解。中位缓解持续时间为8.3（范围3.8-22.4+）个月。中位生存期为16.5（范围1.8-30.5+）个月。3/4级毒性（WHO）在第1周期的29/52（55.8%）患者中出现，在第2周期的6/16（37.5%）患者中出现。主要包括厌食、疲劳、恶心、发热和白细胞减少。我们无法证实阿茨波迪恩等人所描述的用IFN-α、IL-2和5-FU联合治疗转移性肾细胞癌患者的高缓解率。
