Wiesenfeld M, O'Connell M J, Wieand H S, Gonchoroff N J, Donohue J H, Fitzgibbons R J, Krook J E, Mailliard J A, Gerstner J B, Pazdur R
Cedar Rapids Oncology Project Community Clinical Oncology Program, IA, USA.
J Clin Oncol. 1995 Sep;13(9):2324-9. doi: 10.1200/JCO.1995.13.9.2324.
The primary goal of this study was to assess the effectiveness of interferon gamma (IFN-gamma) to prevent tumor relapse following potentially curative surgery in patients with high-risk colon cancer. A secondary goal was to determine the effect of IFN-gamma on immune function and to correlate alterations in immune parameters with survival.
Three to 4 weeks after undergoing resection of all known malignant disease, 99 patients with stage II, III, or IV colon cancer were randomly assigned to receive IFN-gamma 0.2 mg total dose by subcutaneous injection daily for 6 months or observation. Serial assessment of human leukocyte antigen (HLA)-DR expression and Fc receptors on peripheral-blood monocytes was conducted in 24 patients who received IFN-gamma and 27 control patients.
With a median follow-up duration of 59 months in patients still alive, there was evidence of a detrimental effect on time to relapse (P = .03) among patients who received IFN-gamma. There was no significant difference in patient survival (P = .12). This study has sufficient power to rule out a 25% reduction in death rate for patients who received IFN-gamma (P < .05). Significant enhancement of immune function was observed in patients treated with IFN-gamma as measured by HLA-DR expression (P < .01) and Fc receptors (P < .001) on peripheral-blood monocytes.
This study effectively rules out any clinically meaningful benefit for IFN-gamma as surgical adjuvant treatment for patients with high-risk colon cancer. Although significant enhancement of nonspecific immune function was seen with this dosage administration schedule of IFN-gamma, this was not associated with any demonstrable antitumor effect.
本研究的主要目的是评估干扰素γ（IFN-γ）对高危结肠癌患者在可能治愈性手术后预防肿瘤复发的有效性。次要目的是确定IFN-γ对免疫功能的影响，并将免疫参数的改变与生存率相关联。
在切除所有已知恶性病变3至4周后，99例II、III或IV期结肠癌患者被随机分配接受皮下注射总剂量0.2mg的IFN-γ，每日1次，共6个月，或进行观察。对24例接受IFN-γ治疗的患者和27例对照患者进行外周血单核细胞上人类白细胞抗原（HLA）-DR表达和Fc受体的系列评估。
在仍存活的患者中，中位随访时间为59个月，有证据表明接受IFN-γ治疗的患者复发时间受到不利影响（P = 0.03）。患者生存率无显著差异（P = 0.12）。本研究有足够的效力排除接受IFN-γ治疗患者死亡率降低25%的情况（P < 0.05）。通过外周血单核细胞上的HLA-DR表达（P < 0.01）和Fc受体（P < 0.001）测量，接受IFN-γ治疗的患者免疫功能有显著增强。
本研究有效地排除了IFN-γ作为高危结肠癌患者手术辅助治疗的任何临床意义上的益处。尽管按照此剂量给药方案使用IFN-γ可显著增强非特异性免疫功能，但这与任何可证实的抗肿瘤作用无关。
