Elsevier

European Journal of Cancer

Volume 44, Issue 15, October 2008, Pages 2218-2225
European Journal of Cancer

Chemotherapy in metastatic breast cancer: A summary of all randomised trials reported 2000–2007

https://doi.org/10.1016/j.ejca.2008.07.019Get rights and content

Abstract

Aim

To summarise the findings of all randomised trials comparing chemotherapy regimens for metastatic breast cancer that were reported between 2000 and 2007 inclusive.

Methods

We searched the specialised register of clinical trials maintained by the secretariat of the Cochrane Breast Cancer Group (CBCG) from 2000 to 2007, and abstracts from the American Society of Clinical Oncology (ASCO) annual scientific meeting (2000–2007).

Results

Eighty reports of 63 trials were identified as eligible for this review. Whilst over 30% of the trials reported a statistically significant difference in response rate or progression free survival, only 8 trials (13%) reported a difference in overall survival. Thirty percent reported quality of life data. Very few trials examined the critical clinical questions of duration and the relative merits of combination versus sequential single agent chemotherapy.

Concluding statement

There is little evidence from trials reported from 2000 to 2007 that major survival differences exist between many commonly employed chemotherapy regimens.

Introduction

For women with metastatic breast cancer, the aims of treatment are to improve quality of life and to prolong survival, without realistic hope of cure. Using anti-cancer treatments to control disease-related symptoms and slow progression of disease, minimising treatment-related toxicity and reducing the intrusion of the disease and treatment on a patient’s life are all important components of clinical care. Metastatic breast cancer is either initially insensitive to endocrine therapy or eventually becomes so, and cytotoxic chemotherapy thus plays an important role in the treatment of most patients.

Many hundreds of randomised trials have been conducted comparing different chemotherapy drugs, doses, combinations, durations and sequences in an attempt to improve patient outcomes. However, because of the quantity and variety of data, drawing conclusions about the best way to use chemotherapy remains difficult.

The Cochrane Breast Cancer Group has facilitated a series of meta-analyses of chemotherapy in metastatic breast cancer in an attempt to clarify the situation (Table 1).1, 2, 3, 4, 5, 6 In terms of drug classes, only taxanes have been shown to provide an overall survival advantage when compared to non-taxane-containing regimens, and this benefit is modest. Time to progression and response rate also favour taxane-containing regimens. In contrast, no overall survival advantage is seen in favour of anthracycline or platinum-containing regimens. Whilst anthracyclines can improve time to progression and response rate, they are associated with significantly more toxicity than non-anthracycline regimens. Platinums are associated with better response rates, but again at the cost of significant toxicity.

Other Cochrane reviews have found a modest survival advantage for combination regimens compared to single agents but with more toxicity, and that the addition of chemotherapy drug or drugs to an established regimen or the use of high-dose chemotherapy with stem-cell support does not result in better overall survival, although modest improvements in progression free survival may be seen at the cost of extra toxicity. Many of these reviews are based on old trials.

We therefore aimed to identify, review and summarise all randomised trials published between 2000 and 2007 that compared chemotherapy regimens for metastatic breast cancer and contained at least 150 patients. We did not attempt a formal meta-analysis on such a heterogeneous collection of trials. We did not examine trials of targeted therapies.

Section snippets

Criteria for selected studies

We selected randomised controlled trials comparing chemotherapy regimens used in women with metastatic breast cancer. We excluded trials testing targeted therapies. In order to exclude small, hypothesis-generating studies, we arbitrarily limited our selections to trials that had greater than or equal to 150 patients.

Search methods

The specialised register maintained by the Secretariat of the Cochrane Breast Cancer Group (CBCG) was searched. Details of the search strategy applied by the Group to create the

Results

There were 2453 references related to randomised trials in breast cancer dated 2000–2007 in the specialised Cochrane database, of which 535 were concerned with metastatic disease. Of these, 180 were designated as addressing chemotherapy questions and 80 reports of 63 trials were identified as eligible for this review (a comparison of chemotherapy regimens with 150 or more randomised patients). Of these, 43 have been published in the peer-reviewed literature and 20 as abstracts only to date (

Discussion

Whilst active and safe doses and combinations of drugs can be reasonably well established in small phase 2 studies, establishing the relative merits of such regimens requires larger randomised studies. Yet there is little evidence from trials reported from 2000 to 2007 that major differences exist between many commonly employed chemotherapy regimens. Meanwhile, major uncertainty exists about the appropriate duration of therapy in what is an incurable disease and about the relative merits of

Conflict of interest statement

None declared.

Acknowledgements

The motivation to conduct this review came from participation in a working party for the National Breast and Ovarian Cancer Centre of Australia. We thank Nicole Holcroft from the Cochrane Breast Cancer Group for conducting the searches of the specialised register.

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