Ethics for end-of-life treatments: Metastatic colorectal cancer is one example

Health Policy

Volumn 109, Issue 1, 2013, Pages 97-103

  Garattini, Livio ^a   Van De Vooren, Katelijne ^a   Zaniboni, Alberto ^b  

^a MARIO NEGRI INSTITUTE FOR PHARMACOLOGICAL RESEARCH   (Italy)

^b Fondazione Poliambulanza   (Italy)

Author keywords

Biological agents; Colorectal cancer; Economic evaluation; Ethics; Health technology assessment

Indexed keywords

BEVACIZUMAB; CETUXIMAB;

ARTICLE; CANCER SURVIVAL; COLORECTAL CANCER; COST EFFECTIVENESS ANALYSIS; DRUG EFFICACY; ECONOMIC EVALUATION; HUMAN; LIFE EXPECTANCY; MEDICAL ETHICS; METASTATIC COLORECTAL CANCER; OVERALL SURVIVAL; QUALITY OF LIFE; SYSTEMATIC REVIEW; TERMINAL CARE;

ANGIOGENESIS INHIBITORS; ANTIBODIES, MONOCLONAL, HUMANIZED; COLORECTAL NEOPLASMS; COST-BENEFIT ANALYSIS; DRUG COSTS; HUMANS; NEOPLASM METASTASIS; TERMINAL CARE; TREATMENT OUTCOME;

EID: 84870880625     PISSN: 01688510     EISSN: 18726054     Source Type: Journal    
DOI: 10.1016/j.healthpol.2012.08.017     Document Type: Article

References (55)

1. European Pharmacovigilance moves forward and changes its rules. Available from: [accessed 14.02.12]. http://www.fdanews.com/ext/files/Conference/RMDSS11presentations/Breckenridge-11-11%20Washington.pdf.
2. Walsh G. Biopharmaceutical benchmarks 2010. Nature Biotechnology 2010, 28(September (9)):917-924.
3. Sullivan R., Peppercorn J., Sikora K., Zalcberg J., Meropol N.J., Amir E., et al. Delivering affordable care in high-income countries. Lancet Oncology 2011, 12(September (10)):933-980.
4. Koleva D., De Compadri P., Virgili G., Nobili A., Garattini L. A critical review of the full economic evaluations of pharmacological treatments for colorectal cancer. Journal of Medical Economics 2008, 11(1):177-197.
5. Jemal A., Bray F., Center M.M., Ferlay J., Ward E., Forman D. Global cancer statistics. CA: A Cancer Journal for Clinicians 2011, 61(March-April (2)):69-90.
6. Tappenden P., Jones R., Paisley S., Carroll C. Systematic review and economic evaluation of bevacizumab and cetuximab for the treatment of metastatic colorectal cancer. Health Technology Assessment 2007, 11(March (12)):1-128. iii-iv.
7. European Medicines and Agency Tenth annual report of the European Medicines Agency 2004, Available from:, [accessed 14.02.12]. http://www.ema.europa.eu/docs/en_GB/document_library/Annual_report/2009/12/WC500016696.pdf.
8. National Cancer Institute at the National Institutes of Health. FDA approval for bevacizumab. Available from: [accessed 14.02.12]. http://www.cancer.gov/cancertopics/druginfo/fda-bevacizumab.
9. Van Cutsem E., Köhne C.H., Hitre E., Zaluski J., Chang Chien C.R., Makhson A., et al. Cetuximab and chemotherapy as initial treatment for metastatic colorectal cancer. New England Journal of Medicine 2009, 360(April (14)):1408-1417.
10. Saltz L.B., Clarke S., Díaz-Rubio E., Scheithauer W., Figer A., Wong R., et al. Bevacizumab in combination with oxaliplatin-based chemtherapy as first-line therapy in metastatic colorectal cancer: a randomized phase III study. Journal of Clinical Oncology 2008, 26(April (12)):2013-2019.
11. Giantonio B.J., Catalano P.J., Meropol N.J., O'Dwyer P.J., Mitchell E.P., Alberts S.R., et al. Bevacizumab in combination with oxaliplatin, fluorouracil, and leucovorin (FOLFOX4) for previously treated metastatic colorectal cancer: results from the Eastern Cooperative Oncology Group Study E3200. Journal of Clinical Oncology 2007, 25(April (12)):1539-1544.
12. National Cancer Institute at the National Institutes of Health. FDA approval for cetuximab. Available from: [accessed 14.02.12]. http://www.cancer.gov/cancertopics/druginfo/fda-cetuximab.
13. European Medicines Agency. Erbitux - EPAR-product information. Available from: [accessed 14.02.12]. http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000558/WC500029119.pdf.
14. European Medicines Agency. Erbitux, procedural steps taken and scientific information after the authorization. Available from: [accessed 14.02.12]. http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Procedural_steps_taken_and_scientific_information_after_authorisation/human/000558/WC500029115.pdf.
15. European Medicines Agency. Assessment report for Erbitux. Available from: [accessed 14.02.12]. http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Assessment_Report_-_Variation/human/000558/WC500029117.pdf.
16. National Institute for Health and Clinical Excellence Cetuximab, bevacizumab and panitumumab for the treatment of metastatic colorectal cancer after firstline chemotherapy. NICE technology appraisal guidance 242 2012, January, Available from:, [accessed 14.02.12]. http://www.nice.org.uk/nicemedia/live/13651/57924/57924.pdf.
17. Bokemeyer C., Bondarenko I., Makhson A., Hartmann J.T., Aparicio J., de Braud F., et al. Fluorouracil, leucovorin, and oxaliplatin with and without cetuximab in the first-line treatment of metastatic colorectal cancer. Journal of Clinical Oncology 2009, 27(February (5)):663-671.
18. Karapetis C.S., Khambata-Ford S., Jonker D.J., O'Callaghan C.J., Tu D., Tebbutt N.C., et al. K-ras mutations and benefit from cetuximab in advanced colorectal cancer. New England Journal of Medicine 2008, 359(October (17)):1757-1765.
19. Sobrero A.F., Maurel J., Fehrenbacher L., Scheithauer W., Abubakr Y.A., Lutz M.P., et al. EPIC: phase III trial of cetuximab plus irinotecan after fluoropyrimidine and oxaliplatin failure in patients with metastatic colorectal cancer. Journal of Clinical Oncology 2008, 26(May (14)):2311-2319.
20. Au H.J., Karapetis C.S., O'Callaghan C.J, Tu D., Moore M.J., Zalcberg J.R., et al. Health-related quality of life in patients with advanced colorectal cancer treated with cetuximab: overall and KRAS-specific results of the NCIC CTG and AGITG CO.17 trial. Journal of Clinical Oncology 2009, 27(April (11)):1822-1828.
21. Andreis F., Rizzi A., Mosconi P., Braun C., Rota L., Meriggi F., et al. Quality of life in colon cancer patients with skin side effects: preliminary results from a monocentric cross sectional study. Health and Quality of Life Outcomes 2010, 15(April (8)):40.
22. Foley K.A., Wang P.F., Barber B.L., Long S.R., Bagalman J.E., Wagner V., et al. Clinical and economic impact of infusion reactions in patients with colorectal cancer treated with cetuximab. Annals of Oncology 2010, 21(July (7)):1455-1461.
23. Okines A., Cunningham D. Current perspective: bevacizumab in colorectal cancer--a time for reappraisal?. European Journal of Cancer 2009, 45(September (14)):2452-2461.
24. Garattini S., Torri V., Floriani I. Cetuximab for metastatic colorectal cancer. New England Journal of Medicine 2009, 361(July (1)):96. author reply 96-7.
25. Wadhawan A., Stephens R., Adams R. Intermittent therapy in the palliative treatment of metastatic colorectal cancer. Expert Review of Anticancer Therapy 2009, 9(January (1)):125-134.
26. Chase J.L. Clinical use of anti-vascular endothelial growth factor monoclonal antibodies in metastatic colorectal cancer. Pharmacotherapy 2008, 28(November (11 Pt 2)):23S-30S.
27. Messersmith W.A., Ahnen D.J. Targeting EGFR in colorectal cancer. New England Journal of Medicine 2008, 359(October (17)):1834-1836.
28. McCormack P.L., Keam S.J. Spotlight on bevacizumab in metastatic colorectal cancer. BioDrugs 2008, 22(5):339-341.
29. McCormack P.L., Keam S.J. Bevacizumab: a review of its use in metastatic colorectal cancer. Drugs 2008, 68(4):487-506.
30. Meads C., Round J., Tubeuf S., Moore D., Pennant M., Bayliss S. Cetuximab for the first-line treatment of metastatic colorectal cancer. Health Technology Assessment 2010, 14(May (Suppl. 1)):1-8.
31. Whyte S., Pandor A., Stevenson M., Rees A. Bevacizumab in combination with fluoropyrimidine-based chemotherapy for the first-line treatment of metastatic colorectal cancer. Health Technology Assessment 2010, 14(October (Suppl. 2)):47-53.
32. Krol M., Koopman M., Uyl-de Groot C., Punt C.J. A systematic review of economic analyses of pharmaceutical therapies for advanced colorectal cancer. Expert Opinion on Pharmacotherapy 2007, 8(June (9)):1313-1328.
33. Yabroff K.R., Schrag D. Challenges and opportunities for use of cost-effectiveness analysis. Journal of the National Cancer Institute 2009, 101(September (17)):1161-1163.
34. Abouammoh M., Sharma S. Ranibizumab versus bevacizumab for the treatment of neovascular age-related macular degeneration. Current Opinion in Ophthalmology 2011, 22(May (3)):152-158.
35. Ferro S.A., Myer B.S., Wolff D.A., Poniewierski M.S., Culakova E., Cosler L.E., et al. Variation in the cost of medications for the treatment of colorectal cancer. American Journal of Managed Care 2008, 14(November (11)):717-725.
36. Tappenden P., Jones R., Paisley S., Carroll C. The cost-effectiveness of bevacizumab in the first-line treatment of metastatic colorectal cancer in England and Wales. European Journal of Cancer 2007, 43(November (17)):2487-2494.
37. Shiroiwa T., Fukuda T., Tsutani K. Cost-effectiveness analysis of bevacizumab combined with chemotherapy for the treatment of metastatic colorectal cancer in Japan. Clinical Therapeutics 2007, 29(October (10)):2256-2267.
38. Shiroiwa T., Fukuda T., Tsutani K. Out-of-pocket payment and cost-effectiveness of XELOX and XELOX plus bevacizumab therapy: from the perspective of metastatic colorectal cancer patients in Japan. International Journal of Clinical Oncology 2010, 15(June (3)):256-262.
39. Norum J. Cetuximab in the treatment of metastatic colorectal cancer: a model-based cost-effectiveness analysis. Journal of Chemotherapy 2006, 18(October (5)):532-537.
40. Annemans L., Van Cutsem E., Humblet Y., Van Laethem J.L., Bleiberg H. Cost-effectiveness of cetuximab in combination with irinotecan compared with current care in metastatic colorectal cancer after failure on irinotecan - a Belgian analysis. Acta Clinica Belgica 2007, 62(November-December (6)):419-425.
41. Starling N., Tilden D., White J., Cunningham D. Cost-effectiveness analysis of cetuximab/irinotecan vs active/best supportive care for the treatment of metastatic colorectal cancer patients who have failed previous chemotherapy treatment. British Journal of Cancer 2007, 96(January (2)):206-212.
42. Mittmann N., Au H.J., Tu D., O'Callaghan C.J., Isogai P.K., Karapetis C.S., et al. Prospective cost-effectiveness analysis of cetuximab in metastatic colorectal cancer: evaluation of National Cancer Institute of Canada Clinical Trials Group CO.17 trial. Journal of the National Cancer Institute 2009, 101(September (17)):1182-1192.
43. Shiroiwa T., Motoo Y., Tsutani K. Cost-effectiveness analysis of KRAS testing and cetuximab as last-line therapy for colorectal cancer. Molecular Diagnosis & Therapy 2010, 14(December (6)):375-384.
44. Blank P.R., Moch H., Szucs T.D., Schwenkglenks M. KRAS and BRAF mutation analysis in metastatic colorectal cancer: a cost-effectiveness analysis from a swiss perspective. Clinical Cancer Research 2011, 17(October (19)):6338-6346.
45. Wong Y.N., Meropol N.J., Speier W., Sargent D., Goldberg R.M., Beck J.R. Cost implications of new treatments for advanced colorectal cancer. Cancer 2009, 115(May (10)):2081-2091.
46. Asseburg C., Frank M., Köhne C.H., Hartmann J.T., Griebsch I., Mohr A., et al. Cost-effectiveness of targeted therapy with cetuximab in patients with K-ras wild-type colorectal cancer presenting with initially unresectable metastases limited to the liver in a German setting. Clinical Therapeutics 2011, 33(April (4)):482-497.
47. European Medicines Agency. Vectibix, authorization details. Available from: [accessed 14.02.12]. http://www.ema.europa.eu/ema/index.jsp%3Fcurl=pages/medicines/human/medicines/000741/human_med_001128.jsp%26jsenabled=true.
48. Cunningham D., Humblet Y., Siena S., Khayat D., Bleiberg H., Santoro A., et al. Cetuximab monotherapy and cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer. New England Journal of Medicine 2004, 351(July (4)):337-345.
49. National Institute for Health and Clinical Excellence Cetuximab for the first-line treatment of metastatic colorectal cancer. NICE technology appraisal guidance 176 2009, August, Available from:, [accessed 14.02.12]. http://www.nice.org.uk/nicemedia/live/12216/45198/45198.pdf.
50. Richards M. A report for the Secretary of State for Health. Improving access to medicines for NHS patients 2008, November, Available from:, [accessed 14.02.12]. http://www.dh.gov.uk/dr_consum_dh/groups/dh_digitalassets/@dh/@en/documents/digitalasset/dh_089952.pdf.
51. Sobrero A., Bruzzi P. Incremental advance or seismic shift? The need to raise the bar of efficacy for drug approval. Journal of Clinical Oncology 2009, 27(December (35)):5868-5873.
52. Saarni S.I., Hofmann B., Lampe K., Lühmann D., Mäkelä M., Velasco-Garrido M., et al. Ethical analysis to improve decision-making on health technologies. Bulletin of the World Health Organization 2008, 86(August (8)):617-623.
53. DeJean D., Giacomini M., Schwartz L., Miller F.A. Ethics in Canadian health technology assessment: a descriptive review. International Journal of Technology Assessment in Health Care 2009, 25:463-469.
54. Duthie K., Bond K. Improving ethics analysis in health technology assessment. International Journal of Technology Assessment in Health Care 2011, 27(January (1)):64-70.
55. Ghislandi S., Apolone G., Garattini L., Ghislandi I. Is EQ-5D a valid measure of HRQoL in patients with movement disorders? A comparison with SF-36 and FIM questionnaires. European Journal of Health Economics 2002, 3(2):125-130.