Zee B, Cole B, Li T, Browman G, James K, Johnston D, Sugano D, Pater J
National Cancer Institute of Canada Clinical Trials Group, Queen's University, Kingston.
J Clin Oncol. 1998 Aug;16(8):2834-9. doi: 10.1200/JCO.1998.16.8.2834.
In a randomized trial conducted by the National Cancer Institute of Canada Clinical Trials Group (NCIC CTG), interferon alpha-2b (IFN) maintenance therapy (2 mU/m2 subcutaneously three times per week) after successful induction with melphalan and prednisone was found to prolong time to progression in patients with multiple myeloma. A favorable effect on survival was also present, but this difference was of borderline significance. However, IFN toxicity was a concern. To evaluate the trade-off between the clinical benefits of IFN and the associated toxicity, we applied the method of quality-adjusted time without symptoms or toxicity (Q-TWiST).
Three clinical health states were defined in this analysis: time with toxicity (TOX), time without disease relapse or toxicity (TWiST), and time following disease relapse (REL). Toxicity information for IFN had been collected using patient-completed diaries so the actual duration of each adverse event could be determined. The health states TOX and REL were weighted using utility scores to account for a possible decrement in quality of life, a weighted sum of the health state durations is used as a measure of quality-adjusted time.
The health state durations were calculated at 72 months median follow-up. Patients in the IFN group gained an average of 9.8 months without disease relapse (P = .001) and 5.8 months of overall survival (P = .074) versus the control group. However, the IFN group suffered an average of 4.1 months of moderate or worse toxicity (P < .001).
The clinical benefits of IFN outweigh the negative effects associated with treatment toxicity for a wide range of plausible utilities.
在加拿大国家癌症研究所临床试验组（NCIC CTG）进行的一项随机试验中，发现美法仑和泼尼松诱导治疗成功后，使用干扰素α-2b（IFN）维持治疗（2百万单位/平方米，皮下注射，每周三次）可延长多发性骨髓瘤患者的疾病进展时间。对生存率也有有利影响，但这种差异具有临界显著性。然而，IFN的毒性是一个问题。为了评估IFN的临床益处与相关毒性之间的权衡，我们应用了无症状或毒性的质量调整时间（Q-TWiST）方法。
本分析定义了三种临床健康状态：毒性期（TOX）、无疾病复发或毒性期（TWiST）和疾病复发后时间（REL）。使用患者填写的日记收集IFN的毒性信息，以便确定每个不良事件的实际持续时间。使用效用评分对健康状态TOX和REL进行加权，以考虑生活质量可能的下降，健康状态持续时间的加权总和用作质量调整时间的度量。
在中位随访72个月时计算健康状态持续时间。与对照组相比，IFN组患者无疾病复发的时间平均增加9.8个月（P = .001），总生存期平均增加5.8个月（P = .074）。然而，IFN组平均有4.1个月出现中度或更严重的毒性（P < .001）。
对于广泛的合理效用，IFN的临床益处超过了与治疗毒性相关的负面影响。
