Figlin R A, deKernion J B, Mukamel E, Palleroni A V, Itri L M, Sarna G P
Department of Medicine, UCLA School of Medicine.
J Clin Oncol. 1988 Oct;6(10):1604-10. doi: 10.1200/JCO.1988.6.10.1604.
Twenty-one patients with advanced, measurable, renal cell carcinoma (RCC) were administered recombinant interferon alfa-2a (rIFN-alpha 2a) (Roferon-A; Roche Laboratories, Nutley, NJ) intramuscularly beginning at 3 x 10(6) units and escalating to 36 x 10(6) units, 5 d/wk for a total induction period of 14 weeks. rIFN-alpha 2a antibody production was measured using an enzyme immunoassay (EIA). Those sera found to be positive for presence of antibody by the EIA were tested for the presence of neutralizing antibodies (NA) by an antiviral neutralization bioassay (ANB). All patients were evaluable for toxicity, and 19 were evaluable for response and for incidence of antibody formation. Five patients (26%; 95% confidence interval, 6% to 46%) had complete responses (CR) or partial responses (PR) with a median duration of 283 days. An additional ten patients (53%) had minor tumor regressions with a median duration of 86 days. Fifty-one percent of evaluable patients are alive at 18.6 months. Antibodies to rIFN-alpha 2a as measured by the EIA, were detected in 12 (63%) patients. NA were measured in the serum of six (50%) of those EIA-positive patients. Overall, six of 19 patients (32%) developed NA. Median time to the development of antibody as measured by EIA or NA was 8 and 14 weeks, respectively. Median NA titer was 1,200 IFN neutralizing U/mL. NA-positive and -negative patients had a median duration of response of 13.7 v 9.9 months, and survival of greater than 21.3 v 18.3 months, respectively. Clinical toxicity was mild and not therapeutically limiting. Autoantibody production (ANA, rheumatoid factor [RF], Coombs' direct/indirect) occurred in both NA-positive and -negative patients. The clinical significance of the antibodies to rIFN-alpha 2a and the associated autoantibody formation remain unclear; however, presence of antibody was not associated with adverse clinical sequelae.
21例晚期、可测量的肾细胞癌（RCC）患者接受重组干扰素α-2a（rIFN-α 2a）（罗扰素；罗氏实验室，新泽西州纳特利）肌肉注射，起始剂量为3×10⁶单位，每周5天，逐步递增至36×10⁶单位，共诱导14周。采用酶免疫测定法（EIA）检测rIFN-α 2a抗体的产生。那些经EIA检测发现抗体阳性的血清，通过抗病毒中和生物测定法（ANB）检测中和抗体（NA）的存在。所有患者均可评估毒性，19例可评估疗效及抗体形成发生率。5例患者（26%；95%置信区间，6%至46%）出现完全缓解（CR）或部分缓解（PR），中位缓解持续时间为283天。另外10例患者（53%）出现轻度肿瘤退缩，中位持续时间为86天。51%的可评估患者在18.6个月时仍存活。通过EIA检测，12例（63%）患者检测到rIFN-α 2a抗体。在这些EIA阳性患者中的6例（50%）血清中检测到NA。总体而言，19例患者中有6例（32%）产生了NA。通过EIA或NA检测，产生抗体的中位时间分别为8周和14周。NA的中位滴度为1200 IFN中和单位/毫升。NA阳性和阴性患者的中位缓解持续时间分别为13.7个月和9.9个月，中位生存期分别大于21.3个月和18.3个月。临床毒性轻微，不影响治疗。NA阳性和阴性患者均出现自身抗体产生（抗核抗体、类风湿因子[RF]、库姆斯直接/间接试验）。rIFN-α 2a抗体及相关自身抗体形成的临床意义尚不清楚；然而，抗体的存在与不良临床后果无关。
