Ann Intern Med. 1996 Jan 15;124(2):212-22. doi: 10.7326/0003-4819-124-2-199601150-00004.
To evaluate the addition of low-dose interferon-alpha 2b to standard melphalan-prednisone therapy in patients with multiple myeloma.
Randomized, multicenter, phase III study.
15 university hospitals and 92 county hospitals in Sweden, Norway, Denmark, Finland, and Iceland.
583 patients with symptomatic multiple myeloma.
All patients received melphalan-prednisone every 6 weeks. Melphalan-prednisone therapy was interrupted after at least 8 courses in responding patients who achieved a plateau phase, and it was reinstituted at time of relapse. Patients randomly assigned to receive melphalan-prednisone and interferon also received interferon, 5 MU three times weekly, from the start of treatment through response, plateau phase, and relapse, until definitive failure of melphalan-prednisone occurred.
Survival was the main outcome measure. Secondary measures were response rate, response and plateau phase duration, and toxicity. All analyses were done according to the principle of intention-to-treat.
45% of patients receiving melphalan-prednisone and 44% of patients receiving melphalan-prednisone and interferon achieved at least a partial response. Response duration and plateau phase duration were longer for patients receiving melphalan-prednisone and interferon than for patients receiving melphalan-prednisone alone (P < 0.05); the difference in median duration was 5 to 6 months. Toxicity was higher with melphalan-prednisone and interferon, and this led to premature discontinuation of interferon therapy in one third of patients and to a reduced overall dose intensity for melphalan. The median survival time was 29 months for patients receiving melphalan-prednisone and 32 months for patients receiving melphalan-prednisone and interferon. The risk ratio for death for patients receiving melphalan-prednisone compared with patients receiving melphalan-prednisone and interferon was 1.02 (95% CI, 0.89 to 1.40).
Adding continuous low-dose interferon to standard melphalan-prednisone therapy does not improve response rate or survival. However, response duration and plateau phase duration are prolonged by maintenance therapy with interferon.
评估在多发性骨髓瘤患者的标准美法仑 - 泼尼松治疗中添加低剂量干扰素α - 2b的效果。
随机、多中心、III期研究。
瑞典、挪威、丹麦、芬兰和冰岛的15所大学医院和92所县级医院。
583例有症状的多发性骨髓瘤患者。
所有患者每6周接受一次美法仑 - 泼尼松治疗。对于达到平台期的有反应患者，在至少8个疗程后中断美法仑 - 泼尼松治疗，并在复发时重新开始治疗。随机分配接受美法仑 - 泼尼松和干扰素治疗的患者，从治疗开始至缓解、平台期及复发，直至美法仑 - 泼尼松最终治疗失败，还需每周三次接受5 MU干扰素治疗。
生存是主要结局指标。次要指标为缓解率、缓解及平台期持续时间和毒性。所有分析均按照意向性治疗原则进行。
接受美法仑 - 泼尼松治疗的患者中有45%、接受美法仑 - 泼尼松和干扰素治疗的患者中有44%至少达到部分缓解。接受美法仑 - 泼尼松和干扰素治疗的患者的缓解持续时间和平台期持续时间比仅接受美法仑 - 泼尼松治疗的患者更长（P < 0.05）；中位持续时间差异为5至6个月。美法仑 - 泼尼松和干扰素联合治疗的毒性更高，这导致三分之一的患者过早停用干扰素治疗，并降低了美法仑的总体剂量强度。接受美法仑 - 泼尼松治疗的患者中位生存时间为29个月，接受美法仑 - 泼尼松和干扰素治疗的患者为32个月。接受美法仑 - 泼尼松治疗的患者与接受美法仑 - 泼尼松和干扰素治疗的患者相比，死亡风险比为1.02（95%CI，0.89至1.40）。
在标准美法仑 - 泼尼松治疗中添加持续低剂量干扰素并不能提高缓解率或生存率。然而，干扰素维持治疗可延长缓解持续时间和平台期持续时间。
