Technology Appraisal Guidance No. 119
Source: National Institute for Health and Care Excellence
This technology appraisal considers the clinical and cost effectiveness of fludarabine monotherapy only. No recommendations have been made with respect to fludarabine plus cyclophosphamide combination therapy because the current marketing authorisation does not specifically provide a recommendation that fludarabine should be used concurrently with other drugs for the treatment of chronic lymphocytic leukaemia.
Clarification was sought with the MHRA on the issue of the inclusion of the combination of fludarabine and cyclophosphamide in the marketing authorisation of fludarabine. In all correspondence received from the MHRA, including that shared with NICE by Schering Health Care Limited, it has been made clear that ‘the MHRA does not consider that the current marketing authorisations for oral and intravenous (i/v) Fludara (PL/0053/0239 and /0290) specifically provide a recommendation that fludarabine should be used concurrently with other drugs for the treatment of chronic lymphocytic leukaemia’.
The MHRA has further clarified that, in general, it would expect a manufacturer or sponsor to request a variation in the marketing authorisation when: 1. The summary of product characteristics (SPC) in general, and specifically the ‘therapeutic indications’ section, does not contain references to the combination therapy and the company wishes to promote the use of combination therapy, and 2. The use of the combination has implications for the dosage specifications in the ‘posology and method of administration’ section of the SPC.
In the case of fludarabine, the SPCs do not contain references to the combination therapy. With reference to the second point, the dosage of fludarabine (i/v 25 mg/m2 for 3 days and oral 24 mg/m2 for 5 days) in the evidence base for the combination therapy that was submitted by the manufacturer (the CLL4 trial) is different from the fludarabine dosage specified in its SPCs (i/v 25 mg/m2 for 5 days and oral 40 mg/m2 for 5 days).
1.1 Fludarabine monotherapy, within its licensed indication, is not recommended for the first-line treatment of chronic lymphocytic leukaemia.
The guidance shown above constitutes Section 1 of the full document. A copy of the full document and a summary of the evidence is available on the Internet at http://www.nice.org.uk/Guidance/TA119
An abridged version of this guidance (a 'quick reference guide') is also available. Printed copies of the quick reference guide can be obtained by contacting 0845 003 7783 or emailing firstname.lastname@example.org and quoting reference number N1203. It is also available on the Internet at http://www.nice.org.uk/Guidance/TA119/QuickRefGuide/pdf/English
This guidance represents the view of the Institute which was arrived at after careful consideration of the available evidence. Health professionals are expected to fully take it into account when exercising their clinical judgement. This guidance does not, however, override the individual responsibility of health professionals to make appropriate decisions in the circumstances of the individual patient, in consultation with the patient and/or guardian or carer.
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Fludarabine Monotherapy for the First-Line Treatment of Chronic Lymphocytic Leukaemia.
Issue Date: February 2007
Review Date: October 2009