Note from the National Guideline Clearinghouse (NGC): The National Institute for Health and Clinical Excellence (NICE) commissioned an independent academic centre to perform a systematic literature review on the technology considered in this appraisal and prepare an assessment report. The assessment report for this technology appraisal was prepared by The University of Sheffield, School of Health and Related Research [ScHARR]. (See the "Companion Documents" field.)
Identification of Studies
The search strategy aimed to identify all literature relating to the clinical and cost effectiveness of capecitabine and tegafur with uracil for the treatment of metastatic colorectal cancer. The main searches were conducted in April and May 2002.
Fifteen electronic bibliographic databases were searched, covering biomedical, science, social science, health economic and grey literature. A list of databases is provided in Appendix 7.1 of the Assessment Report (see the "Companion Documents" field.
In addition, the reference lists of relevant articles and sponsor submissions were hand-searched and various health services research related resources were consulted via the Internet. These included health economics and health technology assessment (HTA) organisations, guideline producing agencies, generic research and trials registers, and specialist sites. A list of these additional sources is given in Appendix 7.2 of the Assessment Report. Citation searches were conducted on key papers and authors using the Science and Social Science Citation Index facilities.
A combination of free-text and thesaurus terms were used. "Population" search terms (e.g., colorectal, colon, rectum, neoplasm, carcinoma, adenocarcinoma, etc.) were combined with "intervention" terms (e.g., Capecitabine, Xeloda, Fluoropyrimidine, tegafur, uftoral, etc.). Three searches were performed in Medline; the first was the main Medline search, the second was for the epidemiology of colorectal cancer, and the third search was performed to identify further references specifically on the two 5-Fluorouracil regimens (de Gramont and Mayo Clinic). Copies of the search strategies used in the major databases are included in Appendix 7.3 of the Assessment Report.
No language or date restrictions were applied to the searches. The search performed in Medline for the epidemiology of colorectal cancer was limited to 1990-present to ensure that only recent data were reviewed. No language or study/publication type restrictions were applied to the main searches. An economic evaluations filter was used in the main searches performed in Medline and Embase to assist with the identification of articles for the cost effectiveness aspect of the review (refer to Appendix 7.4 of the Assessment Report).
Inclusion and Exclusion Criteria
The titles and abstracts of the papers identified through the search process outlined above were assessed for relevance to the study question using the following criteria.
Inclusion Criteria
Subjects: adults with metastatic colorectal cancer
Intervention: capecitabine or tegafur with uracil plus leucovorin (UFT/LV) used alone as first-line treatment
Comparators: 5-fluorouracil plus leucovorin (5-FU/LV) regimens for metastatic colorectal cancer
Outcome measures to include the following:
- Survival rates
- Progression-free survival
- Tumour response
- Time to treatment failure
- Health-related quality of life
- Adverse events
- Patient preference
- Compliance
- Cost
Methodology, to include at least one of the following:
- Systematic reviews or meta-analyses
- Randomised controlled trials
- Non-randomised studies (for outcomes where no data from randomised controlled trials are available)
- Economic evaluations
Full copies were obtained of all those papers which appeared to be relevant, or which could not be assessed on the basis of the abstract alone.
Exclusion Criteria
Papers describing the use of chemotherapy in an adjuvant setting were excluded. Papers describing randomised phase II trials were excluded where phase III evidence was available.