Huland E, Heinzer H, Mir T S, Huland H
Department of Urology, University of Hamburg, University Clinic Eppendorf, Germany.
Cancer J Sci Am. 1997 Dec;3 Suppl 1:S98-105.
Patients with advanced metastatic renal cell carcinoma often cannot or do not want to tolerate high-dose systemic interleukin-2 (IL-2) therapy and the toxicity associated with it. To reduce toxicity and still maintain or even increase effectiveness, we developed a method to deliver IL-2 locally for the treatment of pulmonary and mediastinal metastases in metastatic renal cell carcinoma patients.
We report here 6 years of experience treating 116 metastatic renal cell carcinoma patients who had pulmonary or mediastinal metastases with inhaled IL-2. We have utilized three different IL-2 preparations (natural human IL-2 purified from the supernatants of mitogen-activated peripheral blood lymphocytes, glycosylated recombinant IL-2 produced by Chinese hamster ovary cells, and non-glycosylated recombinant IL-2 produced by bacteria). All protocols used high-dose inhalation of IL-2, either exclusively (11%), with coadministration of low-dose systemic IL-2 (33%), or with coadministration of low-dose systemic IL-2 and interferon-alpha (56%).
Maximal toxicity per total treatment time was mild (median treatment time, 7.2 months); there was a low incidence (16%) of World Health Organization grade 3 toxicity. Toxicity associated with exclusive inhalation of IL-2 was local and consisted mainly of cough. Thus, patients who could not tolerate high-dose systemic IL-2 were able to tolerate inhalation IL-2 therapy. Progressive pulmonary metastases responded in 15% of patients for a median of 15.5 months (range, 4.1-33 months) and were stabilized in 55% of patients for a median of 6.6 months (range, 3-51.7 months). The overall response rate was 16%; disease was stabilized in 49% of patients and disease progressed in 35% of patients. The overall median response duration was 9.6 months. Median survival was 11.8 months (range, 1.7-68.8 months); expected survival according to risk analysis was 5.3 months.
Inhalation of IL-2 is a nontoxic and effective treatment for patients with progressive pulmonary and mediastinal metastases. Inhaled IL-2 effectively prevented progress of pulmonary metastases in 70% of patients. Furthermore, patients could be treated as outpatients and remain employed. Local administration of IL-2 increases therapeutic effectiveness with little or no toxicity.
晚期转移性肾细胞癌患者通常无法或不愿耐受高剂量全身用白细胞介素-2（IL-2）治疗及其相关毒性。为了降低毒性并仍维持甚至提高疗效，我们开发了一种局部递送IL-2的方法，用于治疗转移性肾细胞癌患者的肺和纵隔转移灶。
我们在此报告了6年中用吸入IL-2治疗116例有肺或纵隔转移的转移性肾细胞癌患者的经验。我们使用了三种不同的IL-2制剂（从丝裂原激活的外周血淋巴细胞上清液中纯化的天然人IL-2、中国仓鼠卵巢细胞产生的糖基化重组IL-2以及细菌产生的非糖基化重组IL-2）。所有方案均采用高剂量吸入IL-2，单独使用（11%）、联合低剂量全身用IL-2（33%）或联合低剂量全身用IL-2和α干扰素（56%）。
每次总治疗时间的最大毒性为轻度（中位治疗时间为7.2个月）；世界卫生组织3级毒性的发生率较低（16%）。单独吸入IL-2相关的毒性是局部性的，主要表现为咳嗽。因此，无法耐受高剂量全身用IL-2的患者能够耐受吸入IL-2治疗。15%的患者肺部进行性转移灶有反应，中位反应持续时间为15.5个月（范围为4.1 - 33个月），55%的患者病情稳定，中位稳定时间为6.6个月（范围为3 - 51.7个月）。总缓解率为16%；49%的患者疾病稳定，35%的患者疾病进展。总中位缓解持续时间为9.6个月。中位生存期为11.8个月（范围为1.7 - 68.8个月）；根据风险分析预期生存期为5.3个月。
吸入IL-2是治疗进行性肺和纵隔转移患者的一种无毒且有效的治疗方法。吸入IL-2有效防止了70%患者肺部转移灶的进展。此外，患者可以作为门诊患者接受治疗并继续工作。局部给予IL-2可提高治疗效果，且毒性很小或无毒性。
