Advertisement

Cost Effectiveness Analysis of Pharmacokinetically-Guided 5-Fluorouracil in FOLFOX Chemotherapy for Metastatic Colorectal Cancer

Published:September 18, 2014DOI:https://doi.org/10.1016/j.clcc.2014.09.007

      Abstract

      Background

      Dosing chemotherapy based on BSA results in marked interindividual variability in drug exposure. A randomized trial showed increased OS and decreased toxicity with PK-guided compared with BSA-based 5-FU dosing in patients with mCRC. The objective of this study was to compare the cost effectiveness of PK-based 5-FU dosing with BSA-based 5-FU dosing in patients with mCRC receiving FOLFOX (5-FU, leucovorin, and oxaliplatin).

      Materials and Methods

      We developed a Markov model to evaluate the cost effectiveness of PK FOLFOX compared with BSA FOLFOX. Progression risks and cause-specific mortality were extrapolated from the fitted survival models. Costs for administration and management of adverse events were estimated based on 2013 Medicare reimbursement rates and average sale prices.

      Results

      PK FOLFOX provided 2.03 QALYs at a cost of $50,205 compared with BSA FOLFOX, which provided 1.46 QALYs at a cost of $37,173. The incremental cost-effectiveness ratio (ICER) was $22,695 per QALY. The ICER remained < $50,000 per QALY in all univariate and multivariate sensitivity analyses.

      Conclusion

      At a $50,000 per QALY threshold, PK FOLFOX is cost effective for mCRC. Because of the cost effectiveness profile and OS advantage with PK FOLFOX, it should be evaluated further in comparative effectiveness studies.

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Clinical Colorectal Cancer
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Ferlay J.
        • Shin H.R.
        • Bray F.
        • Forman D.
        • Mathers C.
        • Parkin D.M.
        Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008.
        Int J Cancer. 2010; 127: 2893-2917
        • Mariotto A.B.
        • Yabroff K.R.
        • Shao Y.
        • Feuer E.J.
        • Brown M.L.
        Projections of the cost of cancer care in the United States: 2010-2020.
        J Natl Cancer Inst. 2011; 103: 117-128
        • Beumer J.H.
        • Chu E.
        • Salamone S.J.
        Body-surface area-based chemotherapy dosing: appropriate in the 21st century?.
        J Clin Oncol. 2012; 30: 3896-3897
        • Saif M.W.
        • Choma A.
        • Salamone S.J.
        • Chu E.
        Pharmacokinetically guided dose adjustment of 5-fluorouracil: a rational approach to improving therapeutic outcomes.
        J Natl Cancer Inst. 2009; 101: 1543-1552
        • Walko C.M.
        • McLeod H.L.
        Will we ever be ready for blood level-guided therapy?.
        J Clin Oncol. 2008; 26: 2078-2079
        • Saam J.
        • Critchfield G.C.
        • Hamilton S.A.
        • Roa B.B.
        • Wenstrup R.J.
        • Kaldate R.R.
        Body surface area-based dosing of 5-fluoruracil results in extensive interindividual variability in 5-fluorouracil exposure in colorectal cancer patients on FOLFOX regimens.
        Clin Colorectal Cancer. 2011; 10: 203-206
        • Beumer J.H.
        • Boisdron-Celle M.
        • Clarke W.
        • et al.
        Multicenter evaluation of a novel nanoparticle immunoassay for 5-fluorouracil on the Olympus AU400 analyzer.
        Ther Drug Monit. 2009; 31: 688-694
        • Gamelin E.
        • Delva R.
        • Jacob J.
        • et al.
        Individual fluorouracil dose adjustment based on pharmacokinetic follow-up compared with conventional dosage: results of a multicenter randomized trial of patients with metastatic colorectal cancer.
        J Clin Oncol. 2008; 26: 2099-2105
        • Capitain O.
        • Asevoaia A.
        • Boisdron-Celle M.
        • Poirier A.L.
        • Morel A.
        • Gamelin E.
        Individual fluorouracil dose adjustment in FOLFOX based on pharmacokinetic follow-up compared with conventional body-area-surface dosing: a phase II, proof-of-concept study.
        Clin Colorectal Cancer. 2012; 11: 263-267
        • Tumeh J.W.
        • Moore S.G.
        • Shapiro R.
        • Flowers C.R.
        Practical approach for using Medicare data to estimate costs for cost-effectiveness analysis.
        Expert Rev Pharmacoecon Outcomes Res. 2005; 5: 153-162
        • Tumeh J.W.
        • Shenoy P.J.
        • Moore S.G.
        • Kauh J.
        • Flowers C.
        A Markov model assessing the effectiveness and cost-effectiveness of FOLFOX compared with FOLFIRI for the initial treatment of metastatic colorectal cancer.
        Am J Clin Oncol. 2009; 32: 49-55
        • Team R.C.
        R: A Language and Environment for Statistical Computing.
        2013 (Available at: http://web.mit.edu/r_v3.0.1/fullrefman.pdf)
        • Sonnenberg F.A.
        • Beck J.R.
        Markov models in medical decision making a practical guide.
        Med Decis Making. 1993; 13: 322-338
        • Tournigand C.
        • Andre T.
        • Achille E.
        • et al.
        FOLFIRI followed by FOLFOX6 or the reverse sequence in advanced colorectal cancer: a randomized GERCOR study.
        J Clin Oncol. 2004; 22: 229-237
        • Hochster H.S.
        • Hart L.L.
        • Ramanathan R.K.
        • et al.
        Safety and efficacy of oxaliplatin and fluoropyrimidine regimens with or without bevacizumab as first-line treatment of metastatic colorectal cancer: results of the TREE Study.
        J Clin Oncol. 2008; 26: 3523-3529
      1. Engauge Digitizer - Digitizing software. Available at: http://digitizer.sourceforge.net. Accessed June 15, 2014.

        • Auget J.L.
        • Balakrishnan N.
        • Mesbah M.
        • Molenberghs G.
        Advances in Statistical Methods for the Health Sciences.
        Springer, Boston2007
        • Arias E.
        United States life tables, 2007.
        Natl Vital Stat Rep. 2011; 59: 1-60
        • Ramsey S.D.
        • Andersen M.R.
        • Etzioni R.
        • et al.
        Quality of life in survivors of colorectal carcinoma.
        Cancer. 2000; 88: 1294-1303
        • Bennouna J.
        • Sastre J.
        • Arnold D.
        • et al.
        Continuation of bevacizumab after first progression in metastatic colorectal cancer (ML18147): a randomised phase 3 trial.
        Lancet Oncol. 2013; 14: 29-37
        • Aballea S.
        • Chancellor J.V.
        • Raikou M.
        • et al.
        Cost-effectiveness analysis of oxaliplatin compared with 5-fluorouracil/leucovorin in adjuvant treatment of stage III colon cancer in the US.
        Cancer. 2007; 109: 1082-1089
      2. Centers for Disease Control and Prevention. FastStats Homepage. Available at: http://www.cdc.gov/nchs/fastats/. Accessed June 15, 2014.

      3. CMS.gov. Centers for Medicare & Medicaid Services. 2013 ASP Drug Pricing Files. Available at: http://www.cms.gov/Medicare/Medicare-Fee-for-Service-Part-B-Drugs/McrPartBDrugAvgSalesPrice/2013ASPFiles.html. Accessed June 15, 2014.

      4. CMS.gov. Centers for Medicare & Medicaid Services. Medicare physician fee schedule. Available at: http://www.cms.gov/apps/physician-fee-schedule/. Accessed September 1, 2013.

        • Goulart B.
        • Ramsey S.
        A trial-based assessment of the cost-utility of bevacizumab and chemotherapy versus chemotherapy alone for advanced non-small cell lung cancer.
        Value Health. 2011; 14: 836-845
        • van Staveren M.C.
        • Guchelaar H.J.
        • van Kuilenburg A.B.
        • Gelderblom H.
        • Maring J.G.
        Evaluation of predictive tests for screening for dihydropyrimidine dehydrogenase deficiency.
        Pharmacogenomics J. 2013; 13: 389-395
        • Yen J.L.
        • McLeod H.L.
        Should DPD analysis be required prior to prescribing fluoropyrimidines?.
        Eur J Cancer. 2007; 43: 1011-1016
        • Lamond N.W.
        • Skedgel C.
        • Rayson D.
        • Lethbridge L.
        • Younis T.
        Cost-utility of the 21-gene recurrence score assay in node-negative and node-positive breast cancer.
        Breast Cancer Res Treat. 2012; 133: 1115-1123
        • Holt S.
        • Bertelli G.
        • Humphreys I.
        • et al.
        A decision impact, decision conflict and economic assessment of routine Oncotype DX testing of 146 women with node-negative or pNImi, ER-positive breast cancer in the U.K..
        Br J Cancer. 2013; 108: 2250-2258
        • Blohmer J.U.
        • Rezai M.
        • Kummel S.
        • et al.
        Using the 21-gene assay to guide adjuvant chemotherapy decision-making in early-stage breast cancer: a cost-effectiveness evaluation in the German setting.
        J Med Econ. 2013; 16: 30-40
        • Behl A.S.
        • Goddard K.A.
        • Flottemesch T.J.
        • et al.
        Cost-effectiveness analysis of screening for KRAS and BRAF mutations in metastatic colorectal cancer.
        J Natl Cancer Inst. 2012; 104: 1785-1795