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The clinical and economic benefits of capecitabine and tegafur with uracil in metastatic colorectal cancer |
Ward S E, Kaltenthaler E, Cowan J, Marples M, Orr B, Seymour M T |
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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. Health technology Two oral treatments for metastatic colorectal cancer (CRC) were investigated. The two treatments were capecitabine (Xeloda; Roche) and UFT/LV (tegafur with uracil in combination with leucovorin; Uftoral; Bristol-Myers Squibb). These were compared with standard intravenous 5-fluorouracil (5-FU) regimens and two infusion regimens (the de Gramont and the modified de Gramont).
Economic study type Cost-effectiveness analysis.
Study population The study population comprised patients with metastatic CRC.
Setting The study setting was secondary care. The economic study was carried out in the UK.
Dates to which data relate The effectiveness data were derived from studies published in 2001 and 2002. The price year was 2002.
Source of effectiveness data The effectiveness data were derived from a review and synthesis of published studies. Further details of the review are given in another publication (Ward et al. 2003, see 'Other Publications of Related Interest' below for bibliographic details).
Outcomes assessed in the review The outcomes assessed in the review were survival rates, progression free-survival, tumour response and time to treatment failure.
Study designs and other criteria for inclusion in the review Only randomised controlled trials (RCTs) or meta-analyses that compared capecitabine or tegafur-uracil with 5-FU/LV regimens as first-line treatment for metastatic CRC were included. The keywords used in the search included colorectal, colon, rectum, neoplasm, carcinoma, adenocarcinoma, capecitabine, Xeloda, fluoropyrimidine, tegafur, Uftoral.
Sources searched to identify primary studies Sources such as Cancerlit, the Cochrane Library, MEDLINE and EMBASE were searched for primary studies. The reference lists of relevant articles were then handsearched.
Criteria used to ensure the validity of primary studies Methods used to judge relevance and validity, and for extracting data Number of primary studies included Five studies were included in the review. Three studies were identified as providing evidence on the use of capecitabine, two being open-label phase III RCTs, and the other a study that pooled data from these two studies. These studies compared treatment with capecitabine and the Mayo regimen (5-FU/LV). Two open-label phase III RCTs of UFT/LV were identified. One compared UFT/LV with the Mayo regimen, whilst the other compared UFT/LV with a modification of the Mayo regimen.
Methods of combining primary studies The authors reported that, owing to the paucity of the data, only a narrative synthesis was undertaken.
Investigation of differences between primary studies Results of the review The results of the review showed that the duration of response and overall survival were not significantly different between capecitabine and 5-FU/LV.
Limited evidence suggested that the de Gramont regimen could be superior to the Mayo regimen in terms of progression-free survival and in relation to toxicity, but that there was no statistically significant survival benefit.
Measure of benefits used in the economic analysis The analysis of benefits was based on the therapeutic equivalence of the treatment alternatives. Therefore, only the costs were considered in the economic analysis.
Direct costs The direct costs included in the analysis were those of the health care system. These covered hospitalisation, outpatient visits, chemotherapy drugs, day-case appointments, district nurse home visits, general practitioner visits and line insertion. Resources used in the administration of the oral chemotherapy and Mayo regimens were taken primarily from trial protocols and were validated against published evidence. The unit costs for drugs were based on the British National Formulary. One-off costs of educating patients on oral therapies and line insertion were derived from a published study. All other costs were derived from Netten et al. 2001 (see 'Other Publications of Related Interest' below for bibliographic details. Since the costs were incurred during 12 months, discounting was not relevant and was thus not performed. The average costs were reported in the study. The price year was 2002.
Statistical analysis of costs The costs were treated as point estimates (i.e. the data were deterministic).
Indirect Costs In line with the perspective adopted, indirect costs were not included.
Sensitivity analysis A series of one-way sensitivity analyses was undertaken. These assessed the impact of varying key parameters as follows:
including an 87% average discount on the price of leucovorin;
changing drug costs to reflect the doses specified in the Summaries of Product Characteristics, rather than from the trials;
estimating total drug costs on the basis of median treatment times in the trials, rather than assuming a 12-week treatment period for all drugs;
varying the costs of outpatient appointments to 86 and 109; and
excluding the costs of adverse event.
Estimated benefits used in the economic analysis See the 'Results of the Review' section.
Cost results The total treatment costs per patient, based on a 12-week period, were:
2,132 with capecitabine;
3,385 with UFT/LV;
3,593 with the Mayo regimen;
3,485 with the modified de Gramont regimen; and
6,255 with the de Gramont regimen.
Synthesis of costs and benefits The costs and benefits were not combined given the therapeutic equivalence of the treatment alternatives. The sensitivity analysis showed that the cost estimates for capecitabine were robust to changes in the cost parameters.
Authors' conclusions Oral therapies resulted in lower costs to the health service than intravenous therapies.
CRD COMMENTARY - Selection of comparators A justification was given for choosing 5-FU/LV as the comparator. At the time of the study, it was the most common first-line treatment for metastatic CRC currently used in the UK. Further, as Mayo, de Gramont and modified de Gramont regimens were also in use in the UK, the authors chose to include these treatments as comparators. You should decide if these treatments are current practice in your own setting.
Validity of estimate of measure of effectiveness The authors reported that a systematic review of the literature was undertaken to identify relevant research and minimise biases. They provided a good overview of the methods used in the review, which were published in a separate article. The authors reported that, in view of the paucity of the data, the studies were combined in a narrative manner. They also reported that there was no direct trial evidence comparing oral drugs with infusion 5-FU regimens. Consequently, a comparison of the Mayo regimen against the infusion regimens was undertaken.
Validity of estimate of measure of benefit The analysis of the benefits was based on the therapeutic equivalence of the treatment alternatives. Therefore, only the costs were considered in the economic analysis.
Validity of estimate of costs All the categories of cost relevant to the health care system perspective were included in the analysis, as were all major relevant costs. Although the authors reported the unit costs for each level of resource use, the costs and the quantities were not reported separately. This will limit the generalisability of the authors' results. Resource use was derived from trial protocols and published evidence. The unit costs were derived from published sources. A limited one-way sensitivity analysis was conducted by varying certain unit costs. Since all costs were incurred during one year, discounting was unnecessary. The price year was reported, which will assist any possible future inflation exercises.
Other issues The authors compared their results with two previous economic evaluations that found UFT/LV regimens to be cost-saving in comparison with 5-FU regimens. The issue of generalisability to other settings was not addressed. The authors do not appear to have presented their results selectively. However, they should have accounted for the uncertainty in the effectiveness and cost results by undertaking probabilistic sensitivity analyses. In their study, the authors did not take the uncertainty surrounding the effectiveness estimates in the literature into consideration. The authors did not report any further limitations relating to their study.
Implications of the study The authors reported that further research should compare the optimum infusion 5-FU regimens with oral drugs, as this would enable treatments to be compared directly in terms of their efficacy, toxicity and quality of life.
Source of funding Funded by the UK NHS Health Technology Assessment Programme.
Bibliographic details Ward S E, Kaltenthaler E, Cowan J, Marples M, Orr B, Seymour M T. The clinical and economic benefits of capecitabine and tegafur with uracil in metastatic colorectal cancer. British Journal of Cancer 2006; 95(1): 27-34 Other publications of related interest Ward S, Kaltenthaler E, Cowan J, et al. Clinical and cost-effectiveness of capecitabine and tegafur with uracil for the treatment of metastatic colorectal cancer: systematic review and economic evaluation. Health Technol Assess 2003;7(32):1-93.
Maroun JA, Asche C, Romeyer F, et al. A cost comparison of oral tegafur plus uracil/folinic acid and parenteral fluorouracil for colorectal cancer in Canada. Pharmacoeconomics 2003;21:1039-51.
Murad AM, de Andrade CA, Delfino C, et al. A pharmacoeconomic comparison of UFT and 5-FU chemotherapy for colorectal cancer in South America. Oncology 1997;11:128-55.
Netten A, Rees T, Harrison G. Unit costs of health and social care 2001. Canterbury: University of Kent, Personal Social Services Research Unit; 2001.
Indexing Status Subject indexing assigned by NLM MeSH Antineoplastic Combined Chemotherapy Protocols /economics /therapeutic use; Capecitabine; Colorectal Neoplasms /drug therapy /economics /secondary; Cost-Benefit Analysis; Deoxycytidine /administration & Fluorouracil /analogs & Great Britain; Humans; Meta-Analysis as Topic; Randomized Controlled Trials as Topic /statistics & State Medicine /economics; Tegafur /administration & Treatment Outcome; Uracil /administration & derivatives; derivatives /economics; dosage /analogs & dosage /economics; dosage /economics; numerical data AccessionNumber 22006001551 Date bibliographic record published 31/01/2007 Date abstract record published 31/01/2007 |
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