Authors' objectives:

To examine the clinical effectiveness and cost-effectiveness of oral capecitabine (Xeloda(R); Roche) for locally advanced and metastatic breast cancer in relation to its licensed indications.

Authors' recommendations: Capecitabine monotherapy: The evidence base for the assessment of the effectiveness of capecitabine monotherapy was particularly poor. All of the studies identified for inclusion in the review lacked a control group, leaving them vulnerable to biases and confounding factors. The evidence from these uncontrolled studies appears to indicate that capecitabine has antitumour activity when used as monotherapy in patients who have received previous treatment with anthracycline-containing regimens and taxanes. The toxicity profile appeared to indicate an increased risk of patients particularly experiencing handfoot syndrome and diarrhoea. QoL was inadequately assessed; only one study included an assessment as part of the evaluation of capecitabine monotherapy. In terms of cost-effectiveness, based on the available data, treatment with capecitabine, compared indirectly with treatment with vinorelbine, appears to be cost-effective. No comparative trials of these treatments were reported. Given the diverse patient population, in terms of disease and treatment history, it is likely that an RCT, comparing survival from point of randomisation for both treatments in a comparative trial, could provide different information on relative survival times. In conclusion, good quality RCTs are urgently needed to compare the effectiveness of capecitabine monotherapy with the alternative third- and subsequent-line therapies currently available, as well as with best supportive care. These data should be collected in a form that facilitates cost-effectiveness analysis. The quality of the economic assessment reflects the poor level of clinical evidence. On the available evidence, capecitabine monotherapy is cost-effective, but there remain serious doubts about whether the quality of the clinical trials invalidates this conclusion. For a more complete picture, systematic reviews of vinorelbine, best supportive care and other relevant comparators in this setting need to be undertaken. Capecitabine in combination with docetaxel: This review suggests that there is limited evidence in the form of RCTs on which to base an assessment of the effectiveness of capecitabine in combination with docetaxel in comparison to existing and new chemotherapy agents for the second-line treatment of advanced breast cancer. Only one RCT was identified for inclusion in the review comparing capecitabine in combination with docetaxel to treatment with single-agent docetaxel. From the evidence available from the single trial, capecitabine in combination with docetaxel appears to be more effective than single-agent docetaxel in terms of overall survival, time to disease progression, time to treatment failure and overall tumour response (complete response plus partial response). There was no statistically significant difference between the two groups in any of the QoL domains. Statistically significant differences between combination and single-agent therapy were identified in terms of reported grade 3/4 treatment-related side-effects. Treatment with capecitabinedocetaxel was associated with higher incidences of handfoot syndrome, nausea, diarrhoea and stomatitis. In terms of costs, combination therapy seems to be cost-effective; however, the cost-effectiveness analysis did not directly consider the impact on QoL associated with the combination and monotherapy treatments themselves. In conclusion, further RCTs investigating capecitabine in combination with docetaxel compared to alternative second-line therapies are required. From the limited evidence it would appear that capecitabine in combination with docetaxel is more effective in terms of median survival time, time to disease progression, time to treatment failure and overall response than single-agent docetaxel. The economic analysis indicates that combination therapy is very likely to be cost-effective. However, the method of calculation of QALYs ignores the potential for differences in adverse events between treatments to alter QoL estimates.

Authors' methods: Systematic review

Project Status: Completed

URL for project: http://www.hta.ac.uk/1317

Year Published: 2004

English language abstract: An English language summary is available

Publication Type: Not Assigned

Country: England, United Kingdom

Organisation Name: NIHR Health Technology Assessment programme

Contact Address: NIHR Journals Library, National Institute for Health and Care Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK

Contact Name: journals.library@nihr.ac.uk

Contact Email: journals.library@nihr.ac.uk

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