The clinical effectiveness and cost-effectiveness of cetuximab (mono- or combination chemotherapy), bevacizumab (combination with non-oxaliplatin chemotherapy) and panitumumab (monotherapy) for the treatment of metastatic colorectal cancer after first-line chemotherapy (review of technology appraisal no. 150 and part review of technology appraisal no. 118): A systematic review and economic model

Health Technology Assessment

Volumn 17, Issue 14, 2013, Pages 1-144

  Hoyle, M ^a   Crathorne, L ^a   Peters, J ^a   Jones Hughes, T ^a   Cooper, C ^a   Napier, M ^b   Tappenden, P ^c   Hyde, C ^a  

^a UNIVERSITY OF EXETER   (United Kingdom)

^b ROYAL DEVON AND EXETER NHS FOUNDATION TRUST   (United Kingdom)

^c UNIVERSITY OF SHEFFIELD   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

ANTINEOPLASTIC AGENT; BEVACIZUMAB; CAPECITABINE; CETUXIMAB; EPIDERMAL GROWTH FACTOR RECEPTOR; FLUOROURACIL; FOLINIC ACID; IRINOTECAN; K RAS PROTEIN; OXALIPLATIN; PANITUMUMAB; PLACEBO;

ABDOMINAL PAIN; ACNE; ACUTE KIDNEY FAILURE; ADULT; AGED; ANOREXIA; ARTICLE; ASTHENIA; BACKACHE; CANCER COMBINATION CHEMOTHERAPY; CANCER EPIDEMIOLOGY; CANCER PROGNOSIS; CANCER SURVIVAL; CLINICAL EFFECTIVENESS; COLORECTAL CANCER; CONFUSION; CONJUNCTIVITIS; CONSTIPATION; COST BENEFIT ANALYSIS; COST EFFECTIVENESS ANALYSIS; COUGHING; DERMATITIS; DIARRHEA; DOSE RESPONSE; DRUG CONTRAINDICATION; DRUG COST; DRUG DOSE INTENSIFICATION; DRUG EFFECT; DRUG ERUPTION; DRUG FATALITY; DRUG HYPERSENSITIVITY; DRUG INDUSTRY; DRUG SAFETY; DRUG SYNTHESIS; DRUG TREATMENT FAILURE; DRUG WITHDRAWAL; DRY SKIN; DYSPNEA; EDEMA; EPISTAXIS; ERYTHEMA; ERYTHRODERMA; EYE DISEASE; FATIGUE; FEMALE; FEVER; FLU LIKE SYNDROME; GENERAL CONDITION DETERIORATION; HEADACHE; HUMAN; HYPERTENSION; HYPOMAGNESEMIA; INFECTION; INFUSION RELATED REACTION; LACRIMATION DISORDER; LUNG EMBOLISM; MAJOR CLINICAL STUDY; MALE; METASTASIS; MONOTHERAPY; NAIL DISEASE; NAUSEA; NEUTROPENIA; ONCOGENE K RAS; OVERALL SURVIVAL; PAIN; PARONYCHIA; PRIMARY HEALTH CARE; PROGRESSION FREE SURVIVAL; PROTEINURIA; PRURITUS; PUSTULE; QUALITY ADJUSTED LIFE YEAR; RANDOMIZED CONTROLLED TRIAL (TOPIC); RECOMMENDED DRUG DOSE; RECTUM HEMORRHAGE; RHINITIS; SIDE EFFECT; SKIN EXFOLIATION; SKIN FISSURE; SKIN TOXICITY; SYSTEMATIC REVIEW; TASTE DISORDER; TREATMENT DURATION; TREATMENT OUTCOME; VOMITING; WILD TYPE;

EID: 84876071518     PISSN: 13665278     EISSN: 20464924     Source Type: Journal    
DOI: 10.3310/hta17140     Document Type: Article

References (91)

1. Herbst RS, Johnson DH, Mininberg E, Carbone DP, Henderson T, Kim ES, et al. Phase I/II trial evaluating the anti-vascular endothelial growth factor monoclonal antibody bevacizumab in combination with the HER-1/epidermal growth factor receptor tyrosine kinase inhibitor erlotinib for patients with recurrent non-small-cell lung cancer. J Clin Oncol 2005;23:2544-2555.
2. Ellis LM. Epidermal growth factor receptor in tumor angiogenesis. Hematol Oncol Clin North Am 2004;18:1007-1021.
3. Vallbohmer D, Zhang W, Gordon M, Yang DY, Yun J, Press OA, et al. Molecular determinants of cetuximab efficacy. J Clin Oncol 2005;23:3536-3544.
4. Kobayashi S, Boggon TJ, Dayaram T, Janne PA, Kocher O, Meyerson M, et al. EGFR mutation and resistance of non-small-cell lung cancer to gefitinib. N Engl J Med 2005;352:786-792.
5. Benvenuti S, Sartore-Bianchi A, Di Nicolantonio F, Zanon C, Moroni M, Veronese S, et al. Oncogenic activation of the RAS/RAF signaling pathway impairs the response of metastatic colorectal cancers to anti-epidermal growth factor receptor antibody therapies. Cancer Res 2007;67:2643-2648.
6. Monzon FA, Ogino S, Hammond ME, Halling KC, Bloom KJ, Nikiforova MN. The role of KRAS mutation testing in the management of patients with metastatic colorectal cancer. Arch Pathol Lab Med 2009;133:1600-1606.
7. Van Cutsem E, Peeters M, Siena S, Humblet Y, Hendlisz A, Neyns B, et al. Open-label phase III trial of panitumumab plus best supportive care compared with best supportive care alone in patients with chemotherapy-refractory metastatic colorectal cancer. J Clin Oncol 2007;25:1658-1664.
8. Cancer Research UK. Bowel (colorectal) cancer - UK incidence statistics; 2011. URL: http://info.cancerresearchuk.org/cancerstats/types/bowel/incidence (accessed 10March 2011).
9. Chapuis PH, Dixon MF, Fielding LP, Gordon PH, Hermanek P, Kyriakos M, et al. Staging of colorectal cancer. Int J Colorectal Dis 1987;2:123-138.
10. 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 Technol Assess 2007;11(12).
11. Cancer Research UK. Bowel (colorectal) cancer - survival statistics; 2011. URL: http://info.cancerresearchuk.org/cancerstats/types/bowel/survival/ (accessed 10 March 2011).
12. Cancer Research UK. Bowel (colorectal) cancer - mortality statistics; 2011. URL: http://info.cancerresearchuk.org/cancerstats/types/bowel/mortality/ (accessed 10 March 2011).
13. National Institute for Health and Clinical Excellence. Guidance for commissioning cancer services: improving outcomes in colorectal cancers. Research evidence for the manual update. London: Centre for Research and Dissemination on behalf of National Cancer Guidance Steering Group; 2004.
14. National Institute for Health and Clinical Excellence (NICE). Irinotecan, oxaliplatin and raltitrexed for the treatment of advanced colorectal cancer. Technology Appraisal 93. London: NICE; 2005.
15. National Institute for Health and Clinical Excellence (NICE). Guidance on the use of capecitabine and tegafur with uracil for metastatic colorectal cancer. Technology Appraisal 61. London: NICE; 2003.
16. National Institute for Health and Clinical Excellence (NICE). Bevacizumab and cetuximab for the treatment of metastatic colorectal cancer. Technology Appraisal 118. London: NICE; 2009.
17. National Institute for Health and Clinical Excellence (NICE). Cetuximab for the first-line treatment of metastatic colorectal cancer. Technology Appraisal 176. London: NICE; 2008.
18. National Institute for Health and Clinical Excellence (NICE). Laparoscopic surgery for colorectal cancer: review of NICE Technology Appraisal 117. Technology Appraisal 105. London: NICE; 2009.
19. National Institute for Health and Clinical Excellence (NICE). Bevacizumab in combination with oxaliplatin and either fluorouracil plus folinic acid or capecitabine for the treatment of metastatic colorectal cancer. Technology Appraisal 212. London: NICE; 2010.
20. National Institute for Health and Clinical Excellence. Clinical Guideline 131 - Colorectal cancer: The diagnosis and management of colorectal cancer. London: NICE; 2004.
21. Association of Coloproctology of Great Britain and Ireland. Guidelines for the management of colorectal cancer. London: ACPGBI; 2007.
22. Shabaruddin FH, Elliott RA, Valle JW, Newman WG, Payne K. Understanding chemotherapy treatment pathways of advanced colorectal cancer patients to inform an economic evaluation in the United Kingdom. Br J Cancer 2010;103:315-323.
23. Grothey A, Sargent D, Goldberg RM, Schmoll HJ. Survival of patients with advanced colorectal cancer improves with the availability of fluorouracil-leucovorin, irinotecan, and oxaliplatin in the course of treatment. J Clin Oncol 2004;22:1209-1214.
24. Roche Products Ltd. Bevacizumab (Avastin) summary of product characteristics. 2010. URL: www.medicines.org.uk/emc/medicine/15748/SPC/ (accessed 4 March 2011).
25. Klement G, Baruchel S, Rak J, Man S, Clark K, Hicklin DJ, et al. Continuous low-dose therapy with vinblastine and VEGF receptor-2 antibody induces sustained tumor regression without overt toxicity. J Clin Invest 2000;105:R15-R24.
26. Hurwitz H, Fehrenbacher L, Novotny W, Cartwright T, Hainsworth J, Heim W, et al. Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med 2004;350:2335-2342.
27. Kabbinavar FF, Schulz J, McCleod M, Patel T, Hamm JT, Hecht JR, et al. Addition of bevacizumab to bolus fluorouracil and leucovorin in first-line metastatic colorectal cancer: results of a randomized phase II trial. J Clin Oncol 2005;23:3697-3705.
28. Merck Serono. Summary of Product Characteristics: Erbitux 5mg/ml solution for infusion. Feltham, Middlesex: Merck Serono; 2010. URL: www.medicines.org.uk/EMC/medicine/19595/SPC/Erbitux+5mg+ml+solution+for+infusion (accessed 4 March 2011).
29. Amgen Ltd. Vectibix summary of product characteristics. 2010. URL: www.medicines.org.uk/EMC/medicine/20528/SPC/Vectibix/ (accessed 4 March 2011).
30. National Institute for Health and Clinical Excellence (NICE). Cetuximab (mono- or combination chemotherapy), bevacizumab (combination with non-oxaliplatin chemotherapy) and panitumumab (monotherapy) for the treatment of metastatic colorectal cancer after firstline chemotherapy (review of technology appraisal 150 and part-review of technology appraisal 118): final scope. London: NICE; 2010.
31. NHS Centre for Reviews and Dissemination. Undertaking systematic reviews of research on effectiveness, 2nd edn. York: NHS Centre for Reviews and Dissemination; 2001.
32. Amado RG, Wolf M, Peeters M, Van Cutsem E, Siena S, Freeman D, et al. Wild-Type KRAS is required for panitumumab efficacy in patients with metastatic colorectal cancer. J Clin Oncol 2008;26:1626-1634.
33. Hurwitz HI, Yi J, Ince W, Novotny WF, Rosen O. The clinical benefit of bevacizumab in metastatic colorectal cancer is independent of K-ras mutation status: analysis of a phase III study of bevacizumab with chemotherapy in previously untreated metastatic colorectal cancer. Oncologist 2009;14:22-28.
34. Bucher HC, Guyatt GH, Griffith LE, Walter SD. The results of direct and indirect treatment comparisons in meta-analysis of randomized controlled trials. J Clin Epidemiol 1997;50:683-691.
35. National Institutes of Health, National Cancer Institute. Common terminology criteria for adverse events (CTCAE). Version 4.0; 2009. URL: www.evs.nci.nih.gov/ftp1/CTCAE/CTCAE_4.03_2010-06-14_QuickReference_5x7.pdf (accessed 16 February 2011).
36. Qiu LX, Mao C, Zhang J, Zhu XD, Liao RY, Xue K, et al. Predictive and prognostic value of KRAS mutations in metastatic colorectal cancer patients treated with cetuximab: a metaanalysis of 22 studies. Eur J Cancer 2010;46:2781-2787.
37. Jonker DJ, O'Callaghan CJ, Karapetis CS, Zalcberg JR, Tu D, Au HJ, et al. Cetuximab for the treatment of colorectal cancer. N Engl J Med 2007;357:2040-2048.
38. Van Cutsem E, Siena S, Humblet Y, Canon JL, Maurel J, Bajetta E, et al. An open-label, single-arm study assessing safety and efficacy of panitumumab in patients with metastatic colorectal cancer refractory to standard chemotherapy. Ann Oncol 2008;19:92-98.
39. Hecht JR, Cohn AL. SPIRITT: a study of second-line treatment of metastatic colorectal cancer with FOLFIRI plus panitumumab or bevacizumab. Community Oncology 2008;5:1-4.
40. Saltz LB, Clarke S, Diaz-Rubio E, Scheithauer W, Figer A, Wong R, et al. Bevacizumab in combination with oxaliplatin-based chemotherapy as first-line therapy in metastatic colorectal cancer: a randomized phase III study. J Clin Oncol 2008;26:2013-2019.
41. Giantonio BJ, Catalano PJ, Meropol NJ, O'Dwyer PJ, Mitchell EP, Alberts SR, 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. J Clin Oncol 2007;25:1539-1544.
42. Mittmann N, Au HJ, Tu D, O'Callaghan CJ, Isogai PK, Karapetis CS, 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. J Natl Cancer Inst 2009;101:1182-1192.
43. Asmis TR, Powell E, Karapetis CS, Jonker DJ, Tu D, Jeffery M, et al. Comorbidity, age and overall survival in cetuximab-treated patients with advanced colorectal cancer (ACRC) - results from NCIC CTG CO.17: a phase III trial of cetuximab versus best supportive care. Ann Oncol 2011;22:118-126.
44. Au HJ, Karapetis CS, O'Callaghan CJ, Tu D, Moore MJ, Zalcberg JR, 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. J Clin Oncol 2009;27:1822-1828.
45. Karapetis C, Khambata-Ford S, Jonker D, O'Callaghan C, Tu D, Vachan B, et al. Kras mutation status is a predictive biomarker for cetuximab benefit in the treatment of advanced colorectal cancer - results from NCIC CTG CO.17: a phase III trial of cetuximab versus best supportive care (33rd Congress of the European Society of Medical Oncology, Stockholm). Ann Oncol 2008;19:82.
46. Therasse P, Arbuck S, Eisenhauer E. New guidelines to evaluate the response to treatment in solid tumors. J Natl Cancer Inst 2000;92:205-216.
47. Karapetis CS, Khambata-Ford S, Jonker DJ, O'Callaghan CJ, Tu D, Tebbutt NC, et al. K-ras mutations and benefit from cetuximab in advanced colorectal cancer. N Engl J Med 2008;359:1757-1765.
48. De Roock W, Piessevaux H, De Schutter J, Janssens M, De Hertogh G, Personeni N, et al. KRAS wild-type state predicts survival and is associated to early radiological response in metastatic colorectal cancer treated with cetuximab. Ann Oncol 2008;19:508-515.
49. 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. N Engl J Med 2004;351:337-345.
50. Tejpar S, Peeters M, Humblet Y. Dose escalation study using up to twice the standard dose of cetuximab in patients with metastatic colorectal cancer (mCRC) with no or slight skin reactions on cetuximab standard dose treatment (EVEREST study): preliminary data. J Clin Oncol 2006;24:159S.
51. Lenz HJ, Van Cutsem E, Khambata-Ford S, Mayer RJ, Gold P, Stella P, et al. Multicenter phase II and translational study of cetuximab in metastatic colorectal carcinoma refractory to irinotecan, oxaliplatin and fluoropyrumidines. J Clin Oncol 2006;24:4914-4921.
52. Peeters M, Siena S, Van Cutsem E, Sobrero A, Hendlisz A, Cascinu S, et al. Association of progression-free survival, overall survival, and patient-reported outcomes by skin toxicity and KRAS status in patients receiving panitumumab monotherapy. Cancer 2009;115:1544-1554.
53. Siena S, Peeters M, Van C, Humblet Y, Conte P, Bajetta E, et al. Association of progressionfree survival with patient-reported outcomes and survival: results from a randomised phase 3 trial of panitumumab. Br J Cancer 2007;97:1469-1474.
54. Tejpar S, Peeters M, Humblet Y, Vermorken JB, De Hertogh G, De Roock W, et al. Relationship of efficacy with KRAS status (wild type versus mutant) in patients with irinotecan-refractory metastatic colorectal cancer (mCRC), treated with irinotecan (q2w) and escalating doses of cetuximab (q1w): The EVEREST experience (preliminary data). J Clin Oncol 2008;26(Suppl.):4001.
55. Tejpar S, Peeters M, Humblet Y, Gelderblom H, Vermorken J, Viret F, et al. Phase I/II study of cetuximab dose-escalation in patients with metastatic colorectal cancer (mCRC) with no or slight skin reactions on cetuximab standard dose treatment (EVEREST): pharmacokinetic (PK), pharmacodynamic (PD) and efficacy data. J Clin Oncol 2007;25(18S):4037.
56. Odom D, Barber B, Bennett L, Peeters M, Zhao Z, Kaye J, et al. Health-related quality of life and colorectal cancer-specific symptoms in patients with chemotherapy-refractory metastatic disease treated with panitumumab. Int J Colorectal Dis 2011;26:173-181.
57. Evers S, Goossens M, de Vet H, van Tulder M, Ament A. Criteria list for assessment of methodological quality of economic evaluations: Consensus on Health Economic Criteria. Int J Technol Assess Health Care 2005;21:240-245.
58. Drummond M, O'Brien B, Stoddart G, Torrance G. Methods for the economic evaluation of health care programmes. Oxford: Oxford University Press; 1997.
59. Annemans L, Van Cutsem E, Humblet Y, Van Laethem JL, 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 Clin Belg 2007;62:419-425.
60. Norum J. Cetuximab in the treatment of metastatic colorectal cancer: a model-based costeffectiveness analysis. J Chemother 2006;18:532-537.
61. 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. Br J Cancer 2007;96:206-212.
62. Wong YN, Meropol NJ, Speier W, Sargent D, Goldberg RM, Beck JR. Cost implications of new treatments for advanced colorectal cancer. Cancer 2009;115:2081-2091.
63. Carlson JJ. Cost-utility of K-RAS mutation testing prior to treatment of metastatic colorectal cancer with cetuximab monotherapy. Value Health 2010;13:A36.
64. Graham CN, Borker R, Oppe M, Uyl-de Groot C, Barber B, Brogan AJ. Colorectal cancer: cost effectiveness of panitumumab plus best supportive care (BSC) compared with BSC alone in chemrefractory metastatic colorectal cancer patients with wild-type KRAS tumour status in the Netherlands. Ann Oncol 2008;19:7-134.
65. Wei DB, Lin CC. The cost-effectiveness of cetuximab use among elderly metastatic colorectal cancer. Value Health 2010;13:A35.
66. Blank PR, Schewenkglenks M, Herrmann R, Moch H, Szucs TD. Cost-effectiveness of novel predictive tests in the treatment of metastatic colorectal cancer: an analysis from a Swiss perspective. J Clin Oncol 2010;28(Suppl. 15):e16549.
67. Tilden D, Thurley D, White J, Aristides M. The cost-effectiveness of cetuximab in combination with irinotecan for the treatment of patients with EGFR-expressing mCRC after failure of irinotecan including cytotoxic therapy in Scotland (PCN17). Value Health 2005;8:A38.
68. Cunningham D, Pyrhonen S, James RD, Punt CJ, Hickish TF, Heikkila R, et al. Randomised trial of irinotecan plus supportive care versus supportive care alone after fluorouracil failure for patients with metastatic colorectal cancer. Lancet 1998;352:1413-1418.
69. Merck Serono. Cetuximab (Erbitux) for the treatment of metastatic colorectal cancer after first line chemotherapy. Report to the National Institute for Health and Clinical Excellence. Feltham: Merck Serono; 2011.
70. Roche. Bevacizumab (combination with non-oxaliplatin chemotherapy) for the treatment of metastatic colorectal cancer after first-line chemotherapy. Roche submission to the National Institute for Health and Clinical Excellence. Welwyn Garden City: Roche; 2011.
71. Amgen. Cetuximab (mono- or combination chemotherapy), bevacizumab (combination with non-oxaliplatin chemotherapy) and panitumumab (monotherapy) for the treatment of metastatic colorectal cancer after first-line chemotherapy (review of technology appraisal 150 and part review of technology appraisal 118). Submission of evidence on panitumumab monotherapy by the manufacturer. Cambridge: Amgen; 2011.
72. National Institute for Health and Clinical Excellence (NICE). Guide to the methods of technology appraisal. London: NICE; 2008.
73. Sobrero Alberto F, editor. Cetuximab plus irinotecan for metastatic colorectal cancer (mCRC): analysis of the first 400 patients in a radnomized Phase III trial (EPIC). ASCO Annual Meeting; 2005, Orlando, FL, USA, abstract.
74. Sobrero Alberto F, Maurel J, Fehrenbacher L, Scheithauer W, Abubakr Yousif A, Lutz Manfred P, et al. EPIC: phase III trial of cetuximab plus irinotecan after fluoropyrimidine and oxaliplatin failure in patients with metastatic colorectal cancer. J Clin Oncol 2008;26:2311-2319.
75. Abubakr Y, Eng C, Pautret J. Cetuximab plus irinotecan for metastatic colorectal cancer (mCRC): safety analysis of 800 patients in a randomised phase III trial (EPIC). J Clin Oncol 2006;24:160S.
76. British Medical Association and Royal Pharmaceutical Society of Great Britain. British national formulary. No. 61, March 2011. London: BMA and RPS; 2011.
77. Department of Health. NHS reference costs 2008-2009. URL: www.dh.gov.uk/en/Publicationsandstatistics/Publications/PublicationsPolicyAndGuidance/DH_111591 (accessed 9 March 2011).
78. Remak E, Brazil L. Cost of managing women presenting with stage IV breast cancer in the United Kingdom. Br J Cancer 2004;91:77-83.
79. Curtis L. Unit costs of health and social care. Canterbury: PPSRU; 2010. URL: www.pssru.ac.uk/uc/uc.htm (accessed 9 March 2011).
80. All Wales Medical Genetics Service. All Wales Medical Genetics Service: KRAS & tumour mutation testing. Cardiff: Cardiff & Vale NHS Trust; 2011. URL: www.wales.nhs.uk/sites3/page.cfm?orgid=525&pid=34097 (accessed 18 March 2011).
81. Ramsey SD, Andersen MR, Etzioni R, Moinpour C, Peacock S, Potosky A, et al. Quality of life in survivors of colorectal carcinoma. Cancer 2000;88:1294-1303.
82. Kind P, Hardman G, Macran S. UK population norms for EQ-5D. Discussion paper. York: Centre for Health Economics; 1999.
83. De Roock WD, Vriendt VD, Normanno N, Ciardiello F, Tejpar S. KRAS, BRAF, PIK3CA, and PTEN mutations: implications for targeted therapies in metastatic colorectal cancer. Lancet Oncol 2011;12:594-603.
84. Ince WL, Jubb AM, Holden SN, Holmgren EB, Tobin P, Sridhar M, et al. Association of k-ras, b-raf, and p53 status with the treatment effect of bevacizumab. J Natl Cancer Inst 2005;97:981-989.
85. Thompson Coon J, Hoyle M, Green C, Liu Z, Welch K, Moxham T, et al. Bevacizumab, sorafenib tosylate, sunitinib and temsirolimus for renal cell carcinoma: a systematic review and economic evaluation. Health Technol Assess 2010;14(2).
86. Lievre A, Bachet JB, Boige V, Cayre A, Le Corre D, Buc E, et al. KRAS mutations as an independent prognostic factor in patients with advanced colorectal cancer treated with cetuximab. J Clin Oncol 2008;26:374-379.
87. Sacco JJ, Botten J, Macbeth F, Bagust A, Clark P. The average body surface area of adult cancer patients in the UK: a multicentre retrospective study. PLoS One 2010;5:e8933.
88. Dubois D, Dubois EF. A formula to estimate the approximate surface area if height and weight be known. Arch Intern Med 1916;17:863-871.
89. Summary of Product Characteristics: Irinotecan Actavis 20mg/ml concentrate for solution for infusion. 2010. URL: www.medicines.org.uk/EMC/medicine/23982/SPC/Irinotecan+Actavis+20mg+ml+concentrate+for+solution+for+infusion/ (accessed 4 March 2011).
90. Brookmeyer R, Crowley J. A Confidence Interval for the Median Survival Time. Biometrics 1982;38:29-41.
91. NHS Employers. NHS terms and conditions of service handbook. Leeds: NHS Employers; 2011. URL: www.nhsemployers.org/PayAndContracts/AgendaForChange/TermsAndConditionsOfServiceHandbook/Pages/Afc-Handbookrp.aspx (accessed 2 March 2011).