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| Capecitabine versus bolus fluorouracil plus leucovorin (folinic acid) as adjuvant chemotherapy for patients with Dukes' C colon cancer: economic evaluation in an Italian NHS setting |
| Di Costanzo F, Ravasio R, Sobrero A, Bertetto O, Vinante O, Luppi G, Labianca R, Amadori D, Barone C, Merlano MC, Longo F, Mansueto G, Antonuzzo L, Gasperoni S |
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Record Status This is a critical abstract of an economic evaluation that meets the criteria for inclusion on NHS EED. Each abstract contains a brief summary of the methods, the results and conclusions followed by a detailed critical assessment on the reliability of the study and the conclusions drawn. CRD summary The objective was to assess the cost-effectiveness of oral capecitabine in comparison with infused fluorouracil plus leucovorin (folinic acid) in patients with Dukes' C colorectal cancer. The authors concluded that capecitabine was a cost-effective alternative to fluorouracil plus leucovorin from the perspective of the Italian National Health Service. The study was based on valid methodology and was satisfactorily reported. A more extensive sensitivity analysis would have enhanced the validity of the authors’ conclusions. Type of economic evaluation Study objective The objective was to assess the cost-effectiveness of oral capecitabine in comparison with infused fluorouracil plus leucovorin (folinic acid) in patients with Dukes' C colorectal cancer. Interventions The two adjuvant chemotherapy regimens were eight cycles of capecitabine (1,250mg/m2 twice daily on days one to 14, every 21 days) and six cycles of rapid-infusion intravenous fluorouracil plus leucovorin (leucovorin 20mg/m2 followed immediately by an intravenous bolus of fluorouracil 425mg/m2 on days one to five, every 28 days). Both treatments lasted 24 weeks. Methods Analytical approach:This economic evaluation was based on a published state-transition decision model. The time horizons were three, four, five, and 10 years, and lifetime. The authors stated that the perspective of the Italian National Health Service (NHS) was adopted.
Effectiveness data:The clinical data came from a large, open-label, multinational, randomised controlled trial (RCT) that enrolled 1,987 eligible patients. There were 1,004 patients in the capecitabine group (median age 62 years; 46% women) and 983 patients in the fluorouracil plus leucovorin group (median age 63 years; 46% women). The median follow-up was 3.8 years. A log-normal distribution was used to extrapolate the clinical endpoints beyond the trial period. The key clinical outcome was survival (overall survival, relapse-free survival, and disease-free survival).
Monetary benefit and utility valuations:The utility values were derived from a published study, the details of which were not given.
Measure of benefit:Quality-adjusted life-months (QALMs) were the summary benefit measure and an annual discount rate of 3.5% was applied.
Cost data:The economic analysis included the costs of: drug acquisition and administration, hospitalisations, emergency room visits, and medications for adverse events. The unit costs and quantities of resources used were reported separately. The patterns of resource consumption were derived from the RCT. The costs were mainly based on Italian published official prices. They were in Euros (EUR) and were discounted at 3.5% per annum. The price year was 2005.
Analysis of uncertainty:A deterministic one-way sensitivity analysis was undertaken by varying the cost of the chemotherapy drug and its administration in order to generate a worst-case scenario for capecitabine (an increase of 25% in drug costs for capecitabine and a simultaneous reduction of 25% for fluorouracil plus leucovorin). Results The gain in QALMs with capecitabine over fluorouracil plus leucovorin was 0.476 at three years, 0.739 at four years, 1.029 at five years, 2.440 at 10 years, and 6.519 over the lifetime. Capecitabine led to a mean cost saving of EUR 2,234 per patient. The drug price and administration costs were the main driver of the cost difference. The higher acquisition cost of capecitabine was more than offset by a reduction in the chemotherapy costs.
The capecitabine regimen was dominant, which means it was both more effective and less expensive than fluorouracil plus leucovorin. The sensitivity analysis confirmed the dominance of capecitabine even in the worst-case scenario. Authors' conclusions The authors concluded that capecitabine was a cost-effective alternative to fluorouracil plus leucovorin from the perspective of the Italian NHS. CRD commentary Interventions:The rationale for the selection of the comparators was clear in that the recently approved chemotherapy was compared against the conventional strategy (Mayo regimen). The dosages and modalities of administration were clearly described.
Effectiveness/benefits:The clinical data came from a large and well conducted RCT, which is usually considered to be a valid source of evidence because of the strengths of its design. Only limited information on the design, methodology, and results of the trial was provided, as it had been published elsewhere, but the basic features of the RCT should ensure valid and robust clinical estimates. The clinical results were appropriately based on an intention-to-treat analysis. Some uncertainty may have been introduced by the statistical method used to extrapolate the trial data after the actual follow-up period. An assessment of this issue in a sensitivity analysis would have been useful. QALMs were appropriate as the benefit measure since they take into account both mortality and morbidity and permit comparisons with other diseases.
Costs:The economic analysis was clearly and transparently presented. The cost categories were appropriate for the perspective stated. All the relevant details on unit costs, resource quantities, the price year, the use of discounting, and the data sources were reported. The transferability of some of the resource use data from the clinical trial to the Italian context was not assessed.
Analysis and results:An appropriate analytic approach was used and the costs and benefits were clearly reported. A synthesis of the costs and benefits was not required because one strategy dominated the other. The issue of uncertainty was only partially investigated in a simple deterministic approach, which focused on the key driver of the model (drug acquisition and administration) and did not assess other inputs. The authors reported the results from another economic evaluation based on data from the RCT in the UK setting and this reached similar conclusions on the superior profile of capecitabine.
Concluding remarks:The study was based on valid methodology and was satisfactorily reported. A more extensive sensitivity analysis would have enhanced the validity of the authors’ conclusions. Funding Supported by Roche SpA, Monza, Italy. Bibliographic details Di Costanzo F, Ravasio R, Sobrero A, Bertetto O, Vinante O, Luppi G, Labianca R, Amadori D, Barone C, Merlano MC, Longo F, Mansueto G, Antonuzzo L, Gasperoni S. Capecitabine versus bolus fluorouracil plus leucovorin (folinic acid) as adjuvant chemotherapy for patients with Dukes' C colon cancer: economic evaluation in an Italian NHS setting. Clinical Drug Investigation 2008; 28(10): 645-655 Other publications of related interest Twelves C, Wong A, Nowacki MP, et al. Capecitabine as adjuvant treatment for stage III colon cancer. New England Journal of Medicine 2005; 352: 2696-2704.
Cassidy J, Douillard JY, Twelves C, et al. Pharmacoeconomic analysis of adjuvant oral capecitabine vs intravenous 5-FU+LV in Dukes’ C colon cancer: the X-ACT trial. British Journal of Cancer 2006; 94: 1122-1129.
Scheithauer W, McKendrick J, Begbie S, et al. Oral capecitabine as an alternative to i.v. 5-fluorouracil-based adjuvant therapy for colon cancer: safety results of a randomized, phase III trial. Annals of Oncology 2003; 14: 1735-1743. Indexing Status Subject indexing assigned by NLM MeSH Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols /administration & Capecitabine; Chemotherapy, Adjuvant /economics /methods; Clinical Trials, Phase III as Topic /economics /methods; Colonic Neoplasms /drug therapy /pathology; Cost-Benefit Analysis; Deoxycytidine /administration & Female; Fluorouracil /administration & Health Care Costs; Humans; Infusions, Parenteral /economics; Italy; Leucovorin /administration & Male; Middle Aged; National Health Programs /economics; Randomized Controlled Trials as Topic /economics /methods; Time Factors; Treatment Outcome; Young Adult; derivatives; derivatives; dosage; dosage /analogs & dosage /analogs & dosage /economics /therapeutic use AccessionNumber 22008102055 Date bibliographic record published 13/05/2009 Date abstract record published 13/01/2010 |
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