Multicenter phase II trial of interleukin-2, interferon-α, and 13-cis-retinoic acid in patients with metastatic renal-cell carcinoma
Multicenter phase II trial of interleukin-2, interferon-α, and 13-cis-retinoic acid in patients with metastatic renal-cell carcinoma
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DOI：
10.1200/jco.1998.16.5.1820
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发表时间：
1998-05-01
影响因子：
45.3
通讯作者：
Vogelzang, NJ
中科院分区：
文献类型：
--
作者：
Stadler, WM;Kuzel, T;Vogelzang, NJ
目的：确定在皮下注射白细胞介素 2 (IL2) 和干扰素 α (IFNA) 门诊治疗方案中添加口服 13-顺式视黄酸 (CRA) 对既往未经治疗的转移性肾细胞癌 (RCC) 患者的缓解率和毒性。 患者和方法： 资格包括体力状态为 2 或更好，无明显终末器官 功能障碍和书面知情同意书。 48 名可评估患者中的 47 名患者的特征包括中位体能状态为 0、68% 的患者既往接受过肾切除术、30% 的患者有一个转移部位、21% 的患者仅有肺转移。治疗包括 IL2 11 x 10(6) IU，每周 4 天，持续 4 周；IFNA 9 x 10(6) IU，每周 2 天，持续 4 周；CRA 1 mg/kg，每天 6 周周期。 结果：47 名患者中有 8 名 (17%) 出现缓解（1 名完全缓解，7 名部分缓解）。通过随后的手术切除，三名部分缓解者不再患病。另外四名患者的肺部或软组织转移出现轻微反应。中位缓解持续时间（包括轻微缓解）为 42 周，中位生存期为 74 周（17 个月），第一个周期期间的 3 级或以上毒性包括流感样症状（21% 的患者）、疲劳（6% 的患者）和恶心和呕吐（15% 的患者）。显着的累积毒性是高脂血症（18 名患者中的 4 名）和心肌病（18 名患者中的 1 名）。有 1 例与治疗相关的死亡。结论：门诊 CRA 加 IL2 和 IFNA 治疗转移性肾细胞癌是可行的，并且有一定效果。中位生存期的延长令人鼓舞，但需要随机试验来证明该组合比单药免疫疗法有所改善。 (C) 1998 年美国临床肿瘤学会。
Purpose: To determine the response rate and toxicity of oral 13-cis-retinoic acid (CRA) added to an outpatient regimen of subcutaneous interleukin-2 (IL2) and interferon-alpha (IFNA) in previously untreated patients with metastatic renal-cell carcinoma (RCC).Patients and Methods: Eligibility included a performance status of 2 or better, no significant end-organ dysfunction, and written informed consent. Characteristics of 47 of 48 assessable patients included a median performance status of 0, prior nephrectomy in 68% of patients, one metastatic site in 30% of patients, and lung-only metastatic disease in 21% of patients. Therapy consisted of IL2 11 x 10(6) IU 4 days per week for 4 weeks, IFNA 9 x 10(6) IU 2 days per week for 4 weeks, and CRA 1 mg/kg daily on a 6-week cycle.Results: Eight of 47 patients (17%) responded (one complete response, seven partial responses). Three partial responders were rendered disease free by subsequent surgical resection. Four additional patients experienced a minor response in lung or soft tissue metastases. The median duration of response, which included minor responses, was 42 weeks, and median survival was 74 weeks (17 months), Grades 3 or greater toxicities during the first cycle included flu-like symptoms (21% of patients), fatigue (6% of patients), and nausea and vomiting (15% of patients), Significant cumulative toxicities were hyperlipidemia (four of 18 patients), and cardiomyopathy (one of 18 patients). There was one therapy-related death.Conclusion: Outpatient CRA plus IL2 and IFNA is feasible and modestly effective in metastatic RCC. The prolonged median survival is encouraging, but randomized trials are required to show that the combination represents an improvement over single-agent immunotherapy. (C) 1998 by American Society of Clinical Oncology.