Pandor, A., Egginton, S., Paisley, S., Tappenden, P. and Sutcliffe, P. (2006) The clinical and cost-effectiveness of oxaliplatin and capecitabine for the adjuvant treatment of colon cancer: systematic review and economic evaluation. Technical Report. Gray Publishing , Tunbridge Wells.
To assess the clinical and cost-effectiveness of oxaliplatin in combination with 5-fluorouracil/ leucovorin (5-FU/LV), and capecitabine monotherapy (within their licensed indications), as adjuvant therapies in the treatment of patients with Stage III (Dukes’ C) colon cancer after complete surgical resection of the primary tumour, as compared with adjuvant chemotherapy with an established fluorouracilcontaining regimen.
Ten electronic bibliographic databases were searched from inception to January 2005. Searches were supplemented by hand searching relevant articles, sponsor and other submissions of evidence to the National Institute of Health and Clinical Excellence and conference proceedings.
A systematic review and metaanalysis (where appropriate) of clinical efficacy evidence and a cost-effectiveness review and economic modelling were carried out. Marginal costs, life years gained and cost-effectiveness acceptability curves were estimated. Probabilistic sensitivity analysis was used to generate information on the likelihood that each of the interventions was optimal.
Three randomised active-controlled trials, of varying methodological quality, were included in the review. The MOSAIC trial and NSABP C-07 study considered the addition of oxaliplatin to adjuvant treatment (albeit administered in different 5-FU/LV regimens) and the X-ACT study compared oral capecitabine with bolus 5-FU/LV alone. A review of the available evidence indicated that in patients with Stage III colon cancer, oxaliplatin in combination with an infusional de Gramont schedule of 5-FU/LV (FOLFOX4) was more effective in preventing and delaying disease recurrence than infusional 5-FU/LV alone (de Gramont regimen). Serious adverse events and treatment discontinuations due to toxicity were more evident with oxaliplatin-based regimens (FOLFOX4 and FLOX regimen) than infusional or bolus 5-FU/LV alone (de Gramont and Roswell Park regimen). Oral capecitabine was at least equivalent in disease-free survival to the bolus Mayo Clinic 5-FU/LV regimen for patients with resected Stage III colon cancer. Although, the safety and tolerability profile of capecitabine was superior to that of the Mayo Clinic 5-FU/LV regimen, it has not been evaluated in comparison with other less toxic 5-FU/LV regimens currently in common use in the UK. Based on the assumptions and survival analysis methods used, the cost-effectiveness analysis using economic modelling estimated that capecitabine was a dominating strategy and resulted in a cost-saving of approximately £3320 per patient in comparison with the Mayo Clinic 5-FU/LV regimen, while also providing an additional 0.98 quality-adjusted life-years (QALYs) over a 50-year model time horizon. Oxaliplatin in combination with 5-FU/LV (FOLFOX4 regimen) is estimated to cost an additional £2970 per QALY gained when compared with the de Gramont 5-FU/LV regimen and demonstrated superior survival outcomes with marginal costs. The uncertainty analysis suggests that both interventions have a high probability of being cost-effective at a threshold of both £20,000 and £30,000. An indirect comparison of the FOLFOX4 and Mayo Clinic 5-FU/LV regimens suggests that the use of FOLFOX4 in place of the Mayo Clinic 5-FU/LV regimen would cost an additional £5777 per QALY gained. An incremental cost-effectiveness ratio (ICER) is estimated to be approximately £13,000 per QALY gained from treatment with FOLFOX4 compared with capecitabine. However, if the Mayo Clinic and the de Gramont 5-FU/LV regimens are assumed to be equivalent in terms of effectiveness, the ICER of FOLFOX4 in comparison with capecitabine may be greater than £30,000 per QALY.
The evidence suggests that both capecitabine and FOLFOX4 are clinically effective and cost-effective in comparison with 5-FU/LV regimens (Mayo Clinic and de Gramont schedules). Further research is suggested into the effectiveness, tolerability, patient acceptability and costs of different oxaliplatin/fluoropyrimidine schedules in the adjuvant setting; the effects of treatment duration on efficacy; adverse events; resource data collection strategies and reporting of summary statistics; subgroups benefiting most from adjuvant chemotherapy; and methods for estimating mean survival.
|Copyright, Publisher and Additional Information:||Copyright: Queen’s Printer and Controller of HMSO 2006 HTA reports may be freely reproduced for the purposes of private research and study and may be included in professional journals provided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Violations should be reported to email@example.com Applications for commercial reproduction should be addressed to HMSO, The Copyright Unit, St Clements House, 2-16 Colegate, Norwich, NR3 1BQ|
|Keywords:||Colon cancer, Colonic neoplasms, Oxaliplatin, Capecitabine, Anti-neoplastic agents, Chemotherapy, Clinical effectiveness, Cost effectiveness, Cost benefit analysis|
|Institution:||The University of Sheffield|
|Academic Units:||The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > School of Health and Related Research (Sheffield)|
|Depositing User:||Diana Papaioannou|
|Date Deposited:||12 Dec 2006|
|Last Modified:||05 May 2015 08:39|
|Identification Number:||ISSN 1366-5278|