Interferon-alpha and survival in metastatic renal carcinoma: early results of a randomised controlled trial
Interferon-alpha and survival in metastatic renal carcinoma: early results of a randomised controlled trial
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干扰素-α 与转移性肾癌的生存：随机对照试验的早期结果
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发表时间：
1999
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通讯作者：
A. Lamont
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作者：
A. Ritchie;G. Griffiths;M. Parmar;S. Fosså;P. Selby;M. Cornbleet;G. Sibley;G. Mead;S. Kaye;Owen;R. Oliver;P. Smith;P. Whelan;P. Cook;P. Fayers;J. Webb;J. Whitehead;A. Lamont
背景：转移性肾癌的2年生存率约为20%，并且对化疗有很大的抵抗力。使用干扰素治疗转移性肾癌仍有争议。虽然非随机研究表明，干扰素生物治疗产生了少量的肿瘤反应，大多数临床医生判断这种治疗是无效的。我们研究了α-干扰素治疗对转移性肾癌住院患者生存率的影响。方法在一项多中心、随机试验中，转移性肾癌患者被随机分配皮下注射α-干扰素，（第一周三次剂量-5 MU、5 MU、10 MU，然后每周三次10 MU，持续11周; n=174）或口服醋酸甲羟孕酮（MPA; 300 mg每日一次，持续12周; n=176）;主要终点为总生存期。试验采用三角序贯设计，一旦结果确定，即提前终止。该试验于1997年11月停止，当时有335例患者（167干扰素-α，168 MPA）的数据。结果共有111例患者在干扰素-α组死亡，125例患者在MPA组死亡。α干扰素组的死亡风险降低了28%（危害比0.72 [95%CI 0.55-0.94]，p=0.017）。干扰素-α使1年生存率提高12%（MPA 31%生存，干扰素-α 43%），中位生存率提高2.5个月（MPA 6个月，干扰素-α 8.5个月）。生物治疗和化疗的联合方案现在应该在随机对照试验中与干扰素单药治疗进行比较。
Background Metastatic renal carcinoma has a 2-year survival of around 20% and is largely resistant to chemotherapy. The use of interferons in the treatment of metastatic renal carcinoma remains controversial. Although non-randomised studies suggest that biological therapy with interferons produces a small number of tumour responses, most clinicians judge such treatment to be ineffective. We have investigated the effect of treatment with interferon-alpha on survival inpatients with metastatic renal carcinoma.Methods In a multicentre, randomised trial, patients with metastatic renal carcinoma were randomly assigned subcutaneous interferon-alpha (three doses-5 MU, 5 MU, 10 MU-for the first week, then 10 MU three times per week for a further 11 weeks; n=174) or oral medroxyprogesterone acetate (MPA; 300 mg once daily for 12 weeks; n=176); The primary endpoint was overall survival. Analysis was by intention to treat. The trial used a triangular sequential design for early termination as soon as results were conclusive. The trial was stopped in November, 1997, when data were available for 335 patients (167 interferon-alpha, 168 MPA).Findings A total of 111 patients have died in the interferon-a group, and 125 patients have died in the MPA group. There was a 28% reduction in the risk of death in the interferon-alpha group (hazard ratio 0.72 [95% CI 0.55-0.94], p=0.017). Interferon-ol gave an improvement in 1-year survival of 12% (MPA 31% survival, interferon-alpha 43%), and an improvement in median survival of 2.5 months (MPA 6 months, interferon-alpha 8.5 months).Interpretation The benefit of treatment with interferon-oc should be weighed against the drug's toxic effects. Combination regimens of biological therapy and chemotherapy should now be compared with interferon-ce monotherapy in randomised controlled trials.