• Takeru Shiroiwa, Takashi Fukuda, and Kiichiro Tsutani.
• Department of Drug Policy and Management, Graduate School of Pharmaceutical Sciences, University of Tokyo, Tokyo, Japan. t.shiroiwa@gmail.com
• Clin Ther. 2007 Oct 1; 29 (10): 2256-67.

BackgroundRapid 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.ObjectiveThe purpose of this cost-effectiveness analysis was to examine the economic efficiency of treating mCRC with bevacizumab plus chemotherapy versus chemotherapy alone in Japan.MethodsWe 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.ResultsWe 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.ConclusionsIn 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.

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