Huland E, Heinzer H, Huland H
Department of Urology, University of Hamburg, University Clinic Eppendorf, Germany.
Hepatogastroenterology. 1999 May;46 Suppl 1:1257-62.
BACKGROUND/AIMS: Risk factors may influence not only prognosis in metastic renal cell carcinoma but also probability of response to immunotherapy. Response of patients treated with inhalation of interleukin-2 (IL-2), which can be offered to those not suitable for systemic therapy, was compared to risk factors. We report on 116 patients who used inhaled IL-2 and were treated in different protocols with natural, recombinant glycosylated and recombinant non-glycosylated.
All protocols had in common a high-dose inhalation of IL-2, either exclusively (11%), with low-dose systemic IL-2 (33%), or with low-dose systemic IL-2 and interferon-alpha (56%). Maximal toxicity per total treatment time (median treatment time: 7.2 months) was mild and there was a low incidence (16%) of WHO grade 3 toxicity. Treatment response was analyzed in a subgroup of patients having at least one given risk factor and treated with recombinant IL-2 (n=86). In all patients having risk factors the following distribution was found: more than 1 metastic location (86%), diagnosis to treatment interval (DTI) <12 months (62%), weight loss prior to therapy (41%), and ECOG performance status > or =2 (13%). In comparison, a group of patients having no risk factors at all was analyzed accordingly.
Response to immunotherapy is dependant on risk factors, the most prominent one being the ECOG. Patients with an ECOG > or =2 achieved no overall response compared to patients with no risk factors who responded to immunotherapy (33%). Progressive pulmonary metastases responded in 15% of patients for a median of 15.5 months (range: 4.133) and were stabilized in 55% for a median of 6.6 months (range: 3-51.7). Overall response rate was 16%, 49%, and 35%, respectively. Median overall response duration was 9.6 months. Median achieved survival was 11.8 months (range: 1.7-68.8).
We conclude that risk factors have to be considered in the interpretation of response to immunotherapy. Exclusion of patients because of risk factors alone does not seem to be justified according to our data. Responses, including long-term stabilization, can be achieved in 27-57% of such patients. IL-2 immunotherapy can also be considered as useful antitumor therapy in patients with risk factors, especially if given without major toxicity.
背景/目的：风险因素不仅可能影响转移性肾细胞癌的预后，还可能影响免疫治疗的反应概率。将吸入白细胞介素-2（IL-2）治疗的患者（可用于不适合全身治疗的患者）的反应与风险因素进行了比较。我们报告了116例使用吸入IL-2并按照不同方案接受天然、重组糖基化和重组非糖基化IL-2治疗的患者。
所有方案的共同点是高剂量吸入IL-2，单独高剂量吸入（11%）、联合低剂量全身IL-2（33%）或联合低剂量全身IL-2和α干扰素（56%）。每个总治疗时间（中位治疗时间：7.2个月）的最大毒性为轻度，世界卫生组织3级毒性的发生率较低（16%）。在一组至少有一个特定风险因素并接受重组IL-2治疗的患者亚组（n = 86）中分析了治疗反应。在所有有风险因素的患者中发现以下分布情况：转移部位超过1个（86%）、诊断至治疗间隔（DTI）<12个月（62%）、治疗前体重减轻（41%）以及东部肿瘤协作组（ECOG）体能状态≥2（13%）。相比之下，相应分析了一组完全没有风险因素的患者。
免疫治疗的反应取决于风险因素，最突出的是ECOG。与无风险因素且对免疫治疗有反应的患者（33%）相比，ECOG≥2的患者未实现总体反应。进行性肺转移在15%的患者中得到反应，中位反应持续时间为15.5个月（范围：4.1 - 33），55%的患者病情稳定，中位稳定时间为6.6个月（范围：3 - 51.7）。总体反应率分别为16%、49%和35%。中位总体反应持续时间为9.6个月。中位总生存期为11.8个月（范围：1.7 - 68.8）。
我们得出结论，在解释免疫治疗反应时必须考虑风险因素。根据我们的数据，仅因风险因素而排除患者似乎没有道理。此类患者中有27% - 57%可实现包括长期病情稳定在内的反应。IL-2免疫治疗也可被视为对有风险因素患者有用的抗肿瘤治疗，尤其是在无重大毒性的情况下给予治疗时。
