New guidance for the NHS published this week recommends docetaxel (Taxotere) to treat women with early, node positive breast cancer after surgery. Use of another taxane, paclitaxel (Taxol), is not recommended in the final guidance.
The guidance, issued by the National Institute for Health and Clinical Excellence (NICE), the body that advises on the use of treatments by the NHS in England and Wales, overturned draft guidance that had recommended against the use of docetaxel.
At the time the appraisal committee found that there was “too much uncertainty about the evidence to make a clear judgment on its clinical and cost effectiveness compared with current practice in England and Wales” (bmj.com, 6 May 2006, News Extra).
NICE asked for more information on the clinical and cost effectiveness of docetaxel in combination with doxorubicin and cyclophosphamide when compared with currently used regimens, including a combination of 5-fluorouracil, cyclophosphamide, and epirubicin (including doses at the higher end of the range currently used in the NHS in England and Wales). It also wanted comparison data for the block sequential regimen of epirubicin followed by a combination of cyclophosphamide, methotrexate, and 5-fluorouracil.
After reviewing further data the appraisal committee concluded that, in terms of disease-free survival and overall survival, docetaxel plus doxorubicin and cyclophosphamide was better than fluorouracil plus doxorubicin and cyclophosphamide. The committee was concerned that the docetaxel regimen resulted in a significantly higher likelihood of grade 3 and 4 adverse events—and in particular febrile neutropenia—but considered that this could be mitigated with granulocyte colony stimulating factor.
The committee concluded that enough evidence existed to conclude that the docetaxel regimen was clinically and cost effective in comparison with standard practice. Hence it recommended the regimen as an alternative option for the adjuvant treatment of early, node positive breast cancer.
However, it did not recommend paclitaxel for the treatment of early, node positive breast cancer after surgery because of the lack of evidence of its clinical and cost effectiveness in comparison with current standard practice in the NHS.
In further guidance NICE recommended rituximab, within its licensed indications (in combination with cyclophosphamide, vincristine, and prednisolone) as an option for the treatment of patients with symptomatic stage III and IV follicular lymphoma who have previously been untreated.
Rituximab is a genetically engineered monoclonal antibody that causes lysis of normal and malignant pre-B and mature B lymphocytes. Follicular lymphoma is the most common type of non-Hodgkin’s lymphoma and affects B lymphocytes.
Most follicular lymphomas present at stage III (involving lymph nodes on both sides of the diaphragm) or stage IV (in which the disease is widespread throughout the body).
The aims of treatment are to achieve remission during relapse and to alleviate symptoms. As most patients lack symptoms in the early phase of the disease, general observation, referred to as “watchful waiting,” is usually used initially.
As the disease progresses and symptoms occur, initial treatment currently starts with a single agent, usually an oral alkylating agent such as chlorambucil. The rituximab combination joins other combination therapies—cyclophosphamide, vincristine, and prednisolone (CVP) and cyclophosphamine, doxorubicin, vincristine, and prednisolone (CHOP)—which are also currently used as first line treatments.
Commenting on the new guidelines, Anna Rigg, a consultant medical oncologist at Guy’s and St Thomas’ NHS Foundation Trust, said: “The NICE ruling on the use of taxane drugs in early breast cancer is a major development. Oncologists now have access to taxanes as part of the chemotherapy for women with early breast cancer if their axillary lymph nodes show evidence of involvement with cancer cells. This had not been possible until now, despite increasing evidence to show that adding taxane drugs to standard chemotherapy can improve survival for node positive breast cancer.
“As most oncologists consider docetaxel to be at least equivalent to paclitaxel, we believe the ruling provides sufficient choice for clinicians managing breast cancer patients. Up to now we have had to fight for this treatment on a case by case basis. However, the NICE ruling does not mention the cost implications for trusts, who will need to develop costing processes to ensure it is available for all eligible patients.”
The guidelines are at www.nice.org.uk/TA109, www.nice.org.uk/TA108, and www.nice.org.uk/TA110.