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.)
Clinical Effectiveness
Identification of Studies
The aim of the search was to provide as comprehensive a retrieval as possible of randomised controlled trials (RCTs) of oxaliplatin or capecitabine as adjuvant therapies in the treatment of colon cancer.
Sources Searched
Nine electronic databases were searched providing coverage of the biomedical and grey literature and current research. The publications lists and current research registers of thirty plus health services research related organisations were consulted via the World Wide Web (WWW). Keyword searching of the WWW was undertaken using the Google search engine. The submissions of evidence to NICE by sponsors were hand-searched as well as references of retrieved papers. A list of the sources searched is provided in Appendix 3 of the Assessment Report (see "Availability of Companion Documents" field).
Keyword Strategies
Sensitive keyword strategies using free-text and, where available, thesaurus terms were developed to search the electronic databases. Synonyms relating to the intervention (oxaliplatin, capecitabine) were combined with synonyms relating to the condition (colon cancer). Keyword strategies for all electronic databases are provided in Appendix 3 of the Assessment Report (see "Availability of Companion Documents" field).
Search Restrictions
A methodological filter aimed at restricting search results to RCTs was used in the searches of Medline, Embase, and Web of Science (WoS). The search of PubMed was restricted to the last 180 days to capture recent and unindexed Medline references. Date limits were not used on any other database. Language restrictions were not used on any database. All searches were undertaken in January 2005.
Inclusion and Exclusion Criteria
Two reviewers independently screened all titles and abstracts. Full paper manuscripts of any titles/abstracts that were considered relevant by either reviewer were obtained where possible. The relevance of each study was assessed according to the criteria set out below. Studies that did not meet all the criteria were excluded and their bibliographic details listed with reasons for exclusion in Appendix 4 of the Assessment Report (see "Availability of Companion Documents" field). Any disagreements were resolved by discussion.
Population
Patients (either gender at any age) with stage III (Dukes' stage C) colon cancer after complete surgical resection of the primary tumour were included.
Interventions
This review covered the effectiveness of the following two alternative chemotherapeutic agents, used within their respective licensed indications:
- Oxaliplatin (Eloxatin®, sanofi-aventis) used in combination with 5-fluorouracil/leucovorin (5-FU/LV)
- Capecitabine (Xeloda®, Roche)
Comparators
The comparator treatment included chemotherapy as adjuvant therapy with an established fluorouracil-containing regimen.
Outcomes
Data on the following outcomes were included:
- Overall survival
- Disease-free or relapse-free survival
- Time to treatment failure
- Adverse effects of treatment/toxicity
- Health-related quality of life (QoL)
Overall survival was defined as the interval from randomisation to death from any cause. Disease-free survival was defined as the time from trial entry or randomisation until recurrence of colorectal cancer or death from any cause. Relapse-free survival was defined in the same way as disease-free survival but excluding deaths unrelated to disease progression or treatment. Time to treatment failure was defined as the interval from randomisation to discontinuation of treatment for any reason (including treatment toxicity and death). Adverse effects of treatment, toxicities, and health-related QoL were abstracted as reported, however defined.
Study Design
Randomised controlled trials that compared oxaliplatin in combination with 5-FU/LV or oral capecitabine, to an adjuvant chemotherapy with an established fluorouracil-containing regimen were included in the assessment of clinical effectiveness.
Cost Effectiveness
Identification of Studies
The aim of the search was to provide as comprehensive a retrieval as possible of economic evaluations of oxaliplatin or capecitabine as adjuvant therapies in the treatment of colon cancer.
Sources Searched
Seven electronic databases were searched providing coverage of the biomedical and health technology assessment literature. The publications lists and current research registers of thirty plus health services research related organisations were consulted via the WWW. Keyword searching of the WWW was undertaken using the Google search engine. The economic assessments submitted by sponsors were identified as studies for inclusion in the review. In addition, the sponsor submissions were hand-searched for further references to studies. A list of the sources searched is provided in Appendix 9 of the Assessment Report (see "Availability of Companion Documents" field).
Keyword Strategies
The keyword strategies developed in the review of clinical effectiveness were used, with the RCT methodological filter being replaced by a filter aimed at restricting search results to economic and cost related studies. Keyword strategies for all electronic databases are provided in Appendix 9 of the Assessment Report (see "Availability of Companion Documents" field).
Search Restrictions
The same limits and restrictions used in the review of clinical effectiveness were applied with the exception of the methodological filter as described above. All searches were undertaken in January 2005.
Inclusion /Exclusion Criteria
Studies were selected for inclusion according to pre-determined inclusion and exclusion criteria. Studies were included if they reported the cost-effectiveness of oxaliplatin or capecitabine in the adjuvant treatment of colorectal cancer. Studies which were considered to be methodologically unsound, that were not reported in sufficient detail or that did not report an estimate of costs-effectiveness (e.g., costing studies) were excluded. Two reviewers independently screened all titles and abstracts. Disagreement was settled through discussion. Full paper manuscripts were obtained for any titles/abstracts that were considered relevant or where the title/abstract information was not sufficient to make a decision.