Authors' objectives:

The objective of this report is to review the effect of GLIADEL wafer on survival and quality of life of patients following primary or recurrent resection of malignant gliomas, to assess the complications of this technology, and to estimate the cost effectiveness and potential budgetary impact of the use of GLIADEL at the MUHC.

The Carmustine implant (GLIADEL wafer) is a local drug delivery system, consisting of a biodegradable polymer wafer impregnated with carmustine (1,3-bis(2-chloroety1);1;nitrosourea; BCNU). It is indicated for use as a treatment of patients with malignant glioma undergoing primary and/or recurrent surgical resection.

Authors' results and conclusions: The overall safety profile for this treatment appears adequate. However, significant adverse effects may not be fully documented due to the small study sizes. There are limited data concerning the efficacy of the carmustine implantable wafers for these indications as only three randomized trials with a total 494 patients have been published. Moreover, there are obvious shortcomings in these trials including small sample sizes, somewhat diverse initial pathology, a lack of control of subsequent therapies and a lack of comparative studies of competing adjunctive therapies. Nevertheless there is fairly consistent evidence of a median survival benefit of approximately 6 - 8 weeks compared to placebo whether the implants were used at the time of a recurrent surgery or administered at the time of initial resection. Regulatory authorities have also concluded that this therapy is efficacious when used with both primary and recurrent surgical resection. While this health benefit may appear marginal, it must be interpreted in the context of a disease with a uniformly poor prognosis. The benefit of other treatment modalities is equally small. A meta-analysis of 12 RCTs of accepted chemotherapeutic strategies for gliomas has shown a similar survival benefit (2 months, 95% CI 1-3). Thus although the clinical benefit is limited, it is comparable to current therapies. No formal cost-effectiveness studies have been performed. However, approximate calculations suggest a cost-effective ratio of approximately $100,000 per life year, a value higher than most currently funded activities, including the standard benchmark of hemodialysis ($85,000/life year). However, this cost-effectiveness is comparable to other current chemotherapeutic regimes (temozolomide) offered to patients with malignant gliomas at the MUHC. Based on these observations and the fact that regulatory authorities accept its efficacy, it would be difficult to justify total refusal of this agent. Furthermore, such decisions must be consistent with societal values and there is a recognized preference for society to give support, even relatively minimal support, to individuals who are severely ill before those who are less ill. Thus the critical issue turns on the economic impact. While a consensus would approve of supporting a limited number of such terminally ill patients at relatively high cost, few would condone such support for a large number, with the associated high opportunity costs and consequent reduction in other hospital services. In the event of patients transferred to the MUHC from other provinces for resection of malignant gliomas and where this therapy may be judged appropriate, authorization from the referring province to cover the costs of the carmustine wafers should be procured before surgery.

Authors' recommendations: Based on the above considerations, the TAU recommends that the use of carmustine implantable wafers at the MUHC, be restricted to a limited number of selected Quebec patients undergoing recurrent resection for malignant glioma and who have had an unsuccessful response to previous standard chemotherapy. The number so supported should not exceed 10 cases per year. Recognizing that the evidence for this therapy is less than ideal, it is recommended that a registry be kept of all patients receiving this therapy so this assessment may be revised in light of accumulating data.

Authors' methods: Systematic review

Project Status: Completed

URL for project: http://www.mcgill.ca/tau/publications/2004

Year Published: 2004

English language abstract: An English language summary is available

Publication Type: Not Assigned

Country: Canada

Organisation Name: Technology Assessment Unit of the McGill University Health Centre (MUHC)

Contact Address: Technology Assessment Unit of the MUHC, Centre for Outcomes Research and Evaluation (CORE), Research Institute of the McGill University Health Centre, 5252 boul. de Maisonneuve, Bureau 3F.50, Montreal, Quebec H4A 3S5

Contact Name: nandini.dendukuri@mcgill.ca

Contact Email: nandini.dendukuri@mcgill.ca

Copyright: Technology Assessment Unit of the McGill University Health Centre (MUHC)