Ratain M J, Priest E R, Janisch L, Vogelzang N J
Department of Medicine, University Chicago Pritzker School of Medicine, Illinois.
Cancer. 1993 Apr 1;71(7):2371-6. doi: 10.1002/1097-0142(19930401)71:7<2371::aid-cncr2820710731>3.0.co;2-1.
Both recombinant interferon alfa and interleukin-2 (IL-2) have been shown to have some activity as single agents in metastatic renal cell cancer (RCC), although their activity is minimal in more common solid tumors. Recent preclinical studies have suggested that the combination of these two agents is especially promising.
Subcutaneous recombinant interferon alfa-2a and IL-2 were administered at one of five dose levels to 33 patients with refractory solid tumors, including 21 patients with RCC. A constant ratio of 5:1 of interferon alfa-2a to IL-2 was used. Interferon alfa-2a and IL-2 were administered three and five times weekly, respectively, for a total of 4 weeks, followed by a rest of 1-3 weeks between cycles.
The dose-limiting toxic effects included hypotension, nephrotoxicity, and fatigue. At the recommended Phase II dose of 7.5 million units (MU)/m2 of interferon alfa-2a and 1.5 MU/m2 of IL-2, 12 patients were treated. Ten of 12 completed the 4-week cycle without modification. Four patients at that dose level had Grade 3-4 toxic effects. Partial responses were observed in 4 of 16 assessable patients with RCC.
Subcutaneous interferon alfa-2a and IL-2 can be self-administered safely on an outpatient basis. At tolerable doses, responses can be achieved in metastatic RCC.
重组干扰素α和白细胞介素-2（IL-2）作为单一药物在转移性肾细胞癌（RCC）中均已显示出一定活性，尽管它们在更常见的实体瘤中的活性极小。最近的临床前研究表明，这两种药物联合使用特别有前景。
将皮下注射重组干扰素α-2a和IL-2以五种剂量水平之一给予33例难治性实体瘤患者，其中包括21例RCC患者。使用干扰素α-2a与IL-2为5:1的固定比例。干扰素α-2a和IL-2分别每周给药三次和五次，共4周，随后在周期之间休息1 - 3周。
剂量限制性毒性作用包括低血压、肾毒性和疲劳。在推荐的II期剂量750万单位（MU）/m²的干扰素α-2a和150万单位/m²的IL-2下，治疗了12例患者。12例中有10例未调整剂量完成了4周周期。该剂量水平的4例患者出现3 - 4级毒性作用。16例可评估的RCC患者中有4例观察到部分缓解。
皮下注射干扰素α-2a和IL-2可在门诊安全地自行给药。在可耐受剂量下，转移性RCC可实现缓解。
