Dutcher Janice P, Fine Jason P, Krigel Robert L, Murphy Barbara A, Schaefer Paul L, Ernstoff Marc S, Loehrer Patrick J
Our Lady of Mercy Cancer Center, NY Med College Bronx, New York 10466, USA.
Med Oncol. 2003;20(3):271-81. doi: 10.1385/MO:20:3:271.
Standard therapy for recurrent or metastatic renal carcinoma includes the biologic response modifiers interferon-alpha (IFN-alpha) and interleukin-2 (IL-2). The response rate for both agents is modest and toxicity is significant. New agents are needed. Interferon-gamma (IFN-gamma) is a type II interferon that demonstrated promising activity in renal carcinoma in early clinical trials. In vitro data suggested synergistic activity when IFN-gamma was combined with IFN-alpha. The Eastern Cooperative Oncology Group conducted a randomized phase II trial to confirm the efficacy of IFN-gamma as a single agent and to evaluate the efficacy and toxicity of IFN-gamma in combination with IFN-alpha in the treatment of patients with metastatic or recurrent renal carcinomas.
Ninety-five patients with recurrent or metastatic renal carcinoma were entered on trial. Patients were stratified based on risk assessment using the Elson method. Patients were randomly assigned to receive either IFN-gamma 0.1 mg/m2 weekly (arm A) or IFN-gamma 0.3 mg/m2 iv daily x 5 every 3 wk plus IFN-alpha 10 MU/m2 daily (arm B). Treatment efficacy was evaluated every 6 weeks.
Toxicity in the arm A was minimal. Significant toxicity was noted in arm B, with four cases of grade 4 neurotoxicity. No responses were seen with IFN-gamma alone. Five responses (two CR and three PR) were noted in the combination arm for an overall response rate of 10%. Four of five responders were classified as "good risk." Median survival for arm A was 7.0 mo vs 10.4 mo for arm B. Risk stratification was significant in arm B.
IFN-gamma at this dose and schedule failed to demonstrate activity in metastatic/recurrent renal carcinoma. The combination of IFN-gamma and IFN-alpha demonstrated a response rate similar to IFN-alpha alone. There was no evidence of synergy between IFN-gamma and IFN-alpha.
复发性或转移性肾癌的标准治疗包括生物反应调节剂α-干扰素（IFN-α）和白细胞介素-2（IL-2）。这两种药物的缓解率一般，且毒性较大。因此需要新的药物。γ-干扰素（IFN-γ）是一种II型干扰素，在早期临床试验中显示出对肾癌有良好的活性。体外数据表明，IFN-γ与IFN-α联合使用具有协同活性。东部肿瘤协作组进行了一项随机II期试验，以确认IFN-γ作为单一药物的疗效，并评估IFN-γ与IFN-α联合治疗转移性或复发性肾癌患者的疗效和毒性。
95例复发性或转移性肾癌患者进入试验。根据埃尔森方法进行风险评估对患者进行分层。患者被随机分配接受以下治疗：A组为每周一次0.1mg/m²的IFN-γ；B组为每3周一次，静脉注射0.3mg/m²的IFN-γ，每日一次，共5天，加每日10MU/m²的IFN-α。每6周评估一次治疗效果。
A组的毒性极小。B组出现明显毒性，有4例4级神经毒性。单独使用IFN-γ未观察到缓解。联合治疗组有5例缓解（2例完全缓解和3例部分缓解），总缓解率为10%。5例缓解者中有4例被归类为“低风险”。A组的中位生存期为7.0个月，B组为10.4个月。B组的风险分层具有显著性。
该剂量和方案的IFN-γ在转移性/复发性肾癌中未显示出活性。IFN-γ与IFN-α联合使用的缓解率与单独使用IFN-α相似。没有证据表明IFN-γ与IFN-α之间存在协同作用。
