Padmanabhan N, Balkwill F R, Bodmer J G, Rubens R D
Br J Cancer. 1985 Jan;51(1):55-60. doi: 10.1038/bjc.1985.8.
Effectiveness of recombinant DNA (rDNA) human interferon alpha 2 (IFN alpha 2) in advanced breast cancer was evaluated in 14 patients who had received prior endocrine and/or cytotoxic therapy. After randomization, 7 patients received IFN alpha 2 two million IU m-2 day-1, s.c., 3 times a week (schedule 1) and 7 patients received 50 million IU m-2 day-1, i.v., for 5 consecutive days, every 3 weeks (schedule 2). Treatment duration was 4-21 weeks in schedule 1 and 6-24 weeks (2-8 courses) in schedule 2. Regressions were not achieved with either schedule. Treatment was associated with significant toxicity and was more severe in schedule 2. Dose limiting toxicities were leukopenia, elevation of liver enzymes, hyperglycemia and fatigue. Serum IFN activity was low or undetectable in patients on schedule 1 and high in patients on schedule 2. At 24 h, serum IFN activity was detectable in only 1/6 patients on schedule 1 as compared to 3/7 patients on schedule 2. IFN neutralizing factors were detected in the serum of only 1 patient prior to treatment but none were detected in any of the patients during or after discontinuation of treatment (4-24 weeks). IFN alpha 2 increased the expression of both HLA class 1 antigens and beta 2 microglobulin in peripheral blood lymphocytes in vivo. This effect was dose related.
在14例先前接受过内分泌和/或细胞毒性治疗的患者中评估了重组DNA（rDNA）人干扰素α2（IFNα2）治疗晚期乳腺癌的有效性。随机分组后，7例患者接受IFNα2，剂量为200万IU/m²，皮下注射，每周3次（方案1）；7例患者接受IFNα2，剂量为5000万IU/m²，静脉注射，连续5天，每3周重复一次（方案2）。方案1的治疗持续时间为4至21周，方案2为6至24周（2至8个疗程）。两种方案均未实现病情缓解。治疗伴有明显毒性，方案2的毒性更严重。剂量限制性毒性为白细胞减少、肝酶升高、高血糖和疲劳。方案1患者的血清IFN活性低或检测不到，方案2患者的血清IFN活性高。在24小时时，方案1的6例患者中只有1例可检测到血清IFN活性，而方案2的7例患者中有3例可检测到。仅在1例患者治疗前的血清中检测到IFN中和因子，但在治疗期间或停药后（4至24周）的任何患者中均未检测到。IFNα2在体内可增加外周血淋巴细胞中HLA-Ⅰ类抗原和β2微球蛋白的表达。这种作用与剂量相关。
