Chemotherapy duration for advanced breast cancer

Cancer ribbon emblemExtract from NHS Evidence: Sept 2011

Overview: Breast cancer is the most common cancer affecting women in Englandand Wales, with about 40,500 new cases diagnosed and 10,900 deaths recorded in Englandand Wales each year.  In men breast cancer is rare, with about 260 cases diagnosed and 68 deaths in England and Wales each year.

Of these new cases in women and men, a small proportion are diagnosed in the advanced stages, when the tumour has spread significantly within the breast or to other organs of the body. In addition, there are a significant number of women who have been previously treated with curative intent who subsequently develop either a local recurrence or metastases.

Current treatment: There is currently no cure for advanced breast cancer. However, treatment can slow tumour growth, relieve symptoms and improve quality of life.

NICE recommends endocrine therapy as first line treatment for the majority of patients with oestrogen receptor-positive advanced breast cancer. Chemotherapy is an option for patients who are not responding to hormone therapy or whose breast cancer is hormone receptor negative.

The NICE Pathway: breast cancer, brings together all related NICE guidance and associated products on the condition in a set of interactive topic-based diagrams.

New evidence: A systematic review and meta-analysis of randomised controlled trials (Gennari et al: Clin Oncol. 2011 Jun 1;29(16):2144-9) evaluated the effect of different first-line chemotherapy durations in patients with advanced breast cancer on overall survival and progression free survival.

The results of trials including 2,269 patients found that longer first-line chemotherapy duration significantly improved both overall and progression free survival.

The team concludes that prolonged chemotherapy administration may be justified given  the survival benefit for some patients. There is a call for more research into treatment schedules which co-administer chemotherapy and targeted agents. The study also suggests considering the administration of sequential single chemotherapeutic agents, each for a planned number of cycles, thus avoiding the cumulative toxicities and the drug resistance associated with the prolonged administration of the same drug.
Commentary: “The current treatment of advanced breast cancer involves the sequential use of chemotherapy, sometimes with targeted agents, as well as hormone therapy. The aim is to prolong survival whilst keeping the toxicity minimal. Where possible, current practice is to continue treatment until progression, (e.g. with oral capecitabine) but for more toxic regimes (e.g. iv docetaxel) treatment beyond 6 cycles is limited due to toxicity.

“In this context, the meta-analysis by Gennari et al suggests an improved  progession free survival and overall survival with  longer duration of first line treatment. This conclusion is somewhat simplistic as the effect of prolonged treatment on toxicity and quality of life is not addressed, nor is the effect of prolonged treatment on response to subsequent treatments made clear. During the period that this study covers, many more RCTs have been performed and it is not clear why these were excluded from the analysis. Also, many new and more effective chemotherapeutic combinations and targeted treatments in use today are not included in the paper.

“Hence, whilst the conclusions of this paper are quite provocative, due to the limitations of the study it is difficult to recommend longer treatment regimes. Indeed the authors do not define the optimum duration of treatment. Therefore the conclusions remain hypothesis generating rather than practice changing.” – Dr Vivek Misra, consultant clinical oncologist at The Christie Hospital.

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