Kilbridge K L, Weeks J C, Sober A J, Haluska F G, Slingluff C L, Atkins M B, Sock D E, Kirkwood J M, Nease R F
Department of Health Evaluation Sciences, University of Virginia Health System, Charlottesville, VA 22908-0821, USA.
J Clin Oncol. 2001 Feb 1;19(3):812-23. doi: 10.1200/JCO.2001.19.3.812.
Although trials of adjuvant interferon alfa-2b (IFN alpha-2b) in high-risk melanoma patients suggest improvement in disease-free survival, it is unclear whether treatment offers improvement in overall survival. Widespread use of adjuvant IFN alpha-2b has been tempered by its significant toxicity. To quantify the trade-offs between IFN alpha-2b toxicity and survival, we assessed patient utilities for health states associated with IFN therapy. Utilities are measures of preference for a particular health state on a scale of 0 (death) to 1 (perfect health).
We assessed utilities for health states associated with adjuvant IFN among 107 low-risk melanoma patients using the standard gamble technique. Health states described four IFN alpha-2b toxicity scenarios and the following three posttreatment outcomes: disease-free health and melanoma recurrence (with or without IFN alpha-2b) leading to cancer death. We also asked patients the improvement in 5-year disease-free survival they would require to tolerate IFN.
Utilities for melanoma recurrence with or without IFN alpha-2b were significantly lower than utilities for all IFN alpha-2b toxicities but were not significantly different from each other. At least half of the patients were willing to tolerate mild-moderate and severe IFN alpha-2b toxicity for 4% and 10% improvements, respectively, in 5-year disease-free survival.
On average, patients rate quality of life with melanoma recurrence much lower than even severe IFN alpha-2b toxicity. These results suggest that recurrence-free survival is highly valued by patients. The utilities measured in our study can be applied directly to quality-of-life determinations in clinical trials of adjuvant IFN alpha-2b to measure the net benefit of therapy.
尽管针对高危黑色素瘤患者的辅助性干扰素α-2b(IFNα-2b)试验表明无病生存期有所改善,但尚不清楚该治疗是否能提高总生存期。辅助性IFNα-2b的广泛应用因其显著的毒性而受到限制。为了量化IFNα-2b毒性与生存期之间的权衡,我们评估了患者对与IFN治疗相关健康状态的效用值。效用值是衡量对特定健康状态的偏好程度的指标,范围从0(死亡)到1(完美健康)。
我们采用标准博弈技术评估了107例低危黑色素瘤患者对与辅助性IFN相关健康状态的效用值。健康状态描述了四种IFNα-2b毒性情况以及以下三种治疗后结果:无病健康状态以及黑色素瘤复发(无论有无IFNα-2b)导致癌症死亡。我们还询问患者为了耐受IFN,他们需要5年无病生存期有多大改善。
无论有无IFNα-2b,黑色素瘤复发的效用值均显著低于所有IFNα-2b毒性情况的效用值,但彼此之间无显著差异。至少一半的患者愿意分别为了5年无病生存期提高4%和10%而耐受轻中度和重度IFNα-2b毒性。
平均而言,患者对黑色素瘤复发的生活质量评分甚至远低于严重的IFNα-2b毒性。这些结果表明无复发生存期受到患者的高度重视。我们研究中测得的效用值可直接应用于辅助性IFNα-2b临床试验中的生活质量测定,以衡量治疗的净效益。