Durie B G, Clouse L, Braich T, Grimm M, Robertone A B
Semin Oncol. 1986 Sep;13(3 Suppl 2):84-8.
Since interferon alfa-2b (Intron A) is useful as a single agent, it is important to determine if interferon can be combined with standard chemotherapy to improve both response and survival in patients with cancer. Using clonogenic assays, interferon was tested alone and in combination with cyclophosphamide (Cytoxan) or melphalan (Alkeran) using several dose and exposure schedules to evaluate cytotoxicity. In vitro, continuous-exposure interferon produced optimal cell kill. Maximum enhancement of cytotoxicity occurred with cyclophosphamide or melphalan pretreatment (1 hour) and/or simultaneous interferon treatment. Based upon these data, a phase I-II study was designed to determine the tolerance of cancer patients to a fixed dose of cyclophosphamide (150 mg/m2 p.o. daily X 4 days [days 2 to 5]) combined with increasing doses of interferon. Interferon was administered subcutaneously on treatment cycle days 1 to 5, plus days 8, 10, 12, 15, 17, and 19 of the 21-day regimen. Three patients had partial responses: one breast cancer, one angiosarcoma, and one myeloma (mixed). All patients reported mild flu-like symptoms, fatigue, and anorexia. Leukopenia occurred in all patients; three required treatment interruption to allow recovery. Eight patients had a fall in hemoglobin (mean decrease 1.4 g/dL). The combination of cyclophosphamide and interferon was safe and deserves further trial in cancer treatment. However, using this combination schedule, interferon doses greater than or equal to 5 X 10(6) IU were poorly tolerated and compromised administration of full-dose cyclophosphamide.
由于干扰素α-2b（安福隆）作为单一药物是有效的，因此确定干扰素是否能与标准化疗联合使用以改善癌症患者的反应率和生存率很重要。使用克隆形成试验，单独测试了干扰素，并将其与环磷酰胺（癌得星）或美法仑（马法兰）联合使用，采用了几种剂量和暴露方案来评估细胞毒性。在体外，持续暴露的干扰素产生了最佳的细胞杀伤效果。环磷酰胺或美法仑预处理（1小时）和/或同时进行干扰素治疗时，细胞毒性增强最大。基于这些数据，设计了一项I-II期研究，以确定癌症患者对固定剂量环磷酰胺（150mg/m²口服，每日×4天[第2至5天]）与递增剂量干扰素联合使用的耐受性。在21天疗程的治疗周期第1至5天，以及第8、10、12、15、17和19天皮下注射干扰素。3例患者出现部分缓解：1例乳腺癌、1例血管肉瘤和1例骨髓瘤（混合型）。所有患者均报告有轻度流感样症状、疲劳和厌食。所有患者均出现白细胞减少；3例患者需要中断治疗以促进恢复。8例患者血红蛋白下降（平均下降1.4g/dL）。环磷酰胺和干扰素联合使用是安全的，值得在癌症治疗中进一步试验。然而，按照这种联合方案，干扰素剂量大于或等于5×10⁶IU时耐受性较差，且影响了全剂量环磷酰胺的给药。
