Shiroiwa Takeru, Fukuda Takashi, Tsutani Kiichiro
Department of Drug Policy and Management, Graduate School of Pharmaceutical Sciences, University of Tokyo, Tokyo, Japan.
Clin Ther. 2007 Oct;29(10):2256-67. doi: 10.1016/j.clinthera.2007.10.013.
Rapid progress has been made in the treatment of metastatic colorectal cancer (mCRC). New treatment regimens for mCRC include not only cytotoxic chemotherapy but also targeted monoclonal antibodies, including bevacizumab. However, bevacizumab is an expensive medication, which costs from 300,000 yen to 400,000 yen (US $2500-$3300) per month.
The purpose of this cost-effectiveness analysis was to examine the economic efficiency of treating mCRC with bevacizumab plus chemotherapy versus chemotherapy alone in Japan.
We searched an electronic database (MEDLINE, UpToDate, and American Society of Clinical Oncology [ASCO] Virtual Meeting; key terms: bevacizumab limited to randomized controlled trial; years: 2000 to present [June 29, 2007]) to detect randomized controlled trials (RCTs) that compared chemotherapy alone with chemotherapy plus bevacizumab. To analyze the cost-effectiveness of bevacizumab, we used the Weibull regression model and determined an expected treatment duration at each state using reported survival curves of RCTs. We included only the direct medical costs (2006) of these medications to estimate the expected values of incremental costs; thus, the analysis was conducted from the perspective of the health care payer. The incremental cost-effectiveness ratios (ICERs) were calculated from these expected values of incremental life-years and incremental costs.
We identified 5 articles using MEDLINE and 1 trial found on UpToDate and ASCO Virtual Meeting; these data composed the final analysis group. First-line chemotherapy regimens included in this analysis were bevacizumab + 5-fluorouracil/leucovorin (FU/LV), irinotecan/FU/LV (IFL), infusional FU/LV/ oxaliplatin (FOLFOX6), bolus FU/LV/oxaliplatin (bFOL), and capecitabine/oxaliplatin (CAPOX). The only second-line chemotherapy regimen included was FOLFOX4. The ICERs of additional bevacizumab when combined with FU/LV,IFL,FOLFOX6, bFOL, and CAPOX were 17.4 million yen (US $145,000), 11.9 million yen ($99,000), 13.5 million yen ($113,000), 16.9 million yen ($141,000), and 8.5 million yen ($71,000), respectively, per life-year gained; the ICER was 14.1 million yen ($118,000) with second-line FOLFOX4.
In this cost-effectiveness analysis in Japan, the ICERs of bevacizumab + FU/LV combination treatment, IFL, and second-line FOLFOX4 were high compared with other chemotherapies for mCRC. It remains difficult to assess first-line therapies comprising bevacizumab with oxaliplatin-based regimens, especially CAPOX. Further information is needed to assess cost-effectiveness.
转移性结直肠癌（mCRC）的治疗已取得快速进展。mCRC的新治疗方案不仅包括细胞毒性化疗，还包括靶向单克隆抗体，如贝伐单抗。然而，贝伐单抗是一种昂贵的药物，每月花费30万至40万日元（2500 - 3300美元）。
本成本效益分析的目的是在日本检验贝伐单抗联合化疗与单纯化疗治疗mCRC的经济效率。
我们检索了一个电子数据库（MEDLINE、UpToDate和美国临床肿瘤学会[ASCO]虚拟会议；关键词：仅限于随机对照试验的贝伐单抗；年份：2000年至今[2007年6月29日]），以查找比较单纯化疗与化疗联合贝伐单抗的随机对照试验（RCT）。为分析贝伐单抗的成本效益，我们使用了威布尔回归模型，并根据RCT报告的生存曲线确定每个状态下的预期治疗持续时间。我们仅纳入这些药物的直接医疗成本（2006年）来估计增量成本的预期值；因此，该分析是从医疗保健支付者的角度进行的。增量成本效益比（ICER）由这些增量生命年和增量成本的预期值计算得出。
我们通过MEDLINE识别出5篇文章，并在UpToDate和ASCO虚拟会议上找到1项试验；这些数据组成了最终分析组。本分析中包括的一线化疗方案有贝伐单抗 + 5 - 氟尿嘧啶/亚叶酸（FU/LV）、伊立替康/FU/LV（IFL）、持续输注FU/LV/奥沙利铂（FOLFOX6）、推注FU/LV/奥沙利铂（bFOL）以及卡培他滨/奥沙利铂（CAPOX）。唯一纳入的二线化疗方案是FOLFOX4。当与FU/LV、IFL、FOLFOX6、bFOL和CAPOX联合使用时，额外使用贝伐单抗每获得一个生命年的ICER分别为1740万日元（145,000美元）、1190万日元（99,000美元）、1350万日元（113,000美元）、1690万日元（141,000美元）和850万日元（71,000美元）；二线使用FOLFOX4时ICER为1410万日元（118,000美元）。
在日本的这项成本效益分析中，与其他mCRC化疗方案相比，贝伐单抗 + FU/LV联合治疗、IFL以及二线FOLFOX4的ICER较高。评估包含贝伐单抗的基于奥沙利铂的一线治疗方案，尤其是CAPOX，仍然困难。需要更多信息来评估成本效益。
