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Combination (several drugs at the same time) versus sequential chemotherapy (same drugs given one after the other) for metastatic breast cancer

Dear RF, McGeechan K, Jenkins MC, Barratt A, Tattersall MHN, Wilcken N
Published Online: 
18 December 2013

Metastatic breast cancer is not currently a curable disease but one that can be very effectively treated with chemotherapy, endocrine therapy and targeted therapies. Average survival is about two years but some women live for many years longer. It is important to investigate the best way to give chemotherapy to treat metastatic breast cancer in order to optimise survival and quality of life and to minimise the side effects from treatment.

This review investigated whether giving a combination of drugs at the same time was more effective than giving the same drugs one at a time (sequential treatment).

A literature search conducted in October 2013 resulted in 12 randomised controlled studies with 2317 patients that could be included in the analysis. The patients had metastatic breast cancer and either they had not been treated or had received one or two treatments after their diagnosis of metastatic breast cancer. The primary outcomes were overall survival and progression-free survival (time from randomisation to the time of disease progression). Secondarily, we compared the degree the tumour shrunk in response to chemotherapy (overall response rate), toxicity and quality of life.

There was no difference in overall survival between the two groups but we found that when drugs were given one at a time there was more time before the tumours grew back again (longer progression-free survival). However, combination chemotherapy caused tumours to shrink more, although this did not result in longer survival than when using sequential chemotherapy. Rates of febrile neutropenia (infection) were higher in the combination arm but there was no difference in the rates of neutropenia (low white blood cells). There was no difference in quality of life between the two groups but there were only three trials that reported this information. Quality of life should be included as an outcome in future trials addressing this question. Overall, the studies did not consistently report the way patients were randomised and this may be a source of bias in the results.

Generally this review supports the recommendations by international guidelines to use sequential monotherapy unless there is rapid disease progression.

This record should be cited as: 
Dear RF, McGeechan K, Jenkins MC, Barratt A, Tattersall MHN, Wilcken N. Combination versus sequential single agent chemotherapy for metastatic breast cancer. Cochrane Database of Systematic Reviews 2013, Issue 12. Art. No.: CD008792. DOI: 10.1002/14651858.CD008792.pub2
Assessed as up to date: 
31 October 2013
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