Addition of drugs to a chemotherapy regimen for metastatic breast cancer

Advanced breast cancer is treatable but not curable. Women with advanced breast cancer have an average survival of about 2 years, although some women may live for many years beyond this. Therefore, it is important to investigate different chemotherapy treatment options. Chemotherapy can improve survival for women with metastatic breast cancer, but it can also cause toxic side effects. Of interest is whether there is any benefit by adding additional chemotherapy drugs, particularly given the potential harm caused by more dose-intensive treatment. This review investigated the value of adding one or more chemotherapy drugs to a chemotherapy regimen. We found that the addition of chemotherapy drug/s to a regimen caused greater shrinkage of the tumour seen with imaging but increased toxicity. There is insufficient evidence to determine if there is an impact on time to disease progression and overall survival.

Authors' conclusions: 

The addition of one or more drugs to the regimen shows a statistically significant advantage for tumour response in women with metastatic breast cancer but the results suggest no difference in survival time or time to progression. The positive effect on tumour response was also associated with increased toxicity.

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Background: 

The addition of a chemotherapy drug or drugs to an established regimen is one method used to increase the dose and intensity of treatment for metastatic breast cancer.

Objectives: 

To assess the effects of adding one or more chemotherapy drugs to an established regimen in women with metastatic breast cancer.

Search strategy: 

We searched the Cochrane Breast Cancer Group's Specialised Register (to August 2009) using the codes for "advanced breast cancer" and "chemotherapy". This review is an update of the original Cochrane Review (Issue 3, 2006).

Selection criteria: 

Randomised trials with a first line regimen of at least two chemotherapy drugs compared to the same regimen plus the addition of one or more chemotherapy drugs in women with metastatic breast cancer.

Data collection and analysis: 

Two authors extracted data independently from published trials. We derived hazard ratios (HR) from time-to-event outcomes where possible, and used a fixed-effect model for meta-analysis. We analysed response rates as dichotomous variables and extracted toxicity data where available.

Main results: 

We identified 17 trials reporting on 22 treatment comparisons (2674 patients randomised). Fifteen trials (20 treatment comparisons) reported results for tumour response and 11 trials (14 treatment comparisons) published time-to-event data for overall survival. There were 1532 deaths in 2116 women randomised to trials of the addition of a drug to the regimen and control (the regimen alone). There was no detectable difference in overall survival between these patients, with an overall HR of 0.96 (95% confidence interval (CI) 0.87 to 1.07, P = 0.47) and no significant heterogeneity. We found no difference in time to progression between these regimens, with an overall HR of 0.93 (95% CI 0.81 to 1.07, P = 0.31) and no significant heterogeneity. Addition of a drug to the regimen was favourably associated with overall tumour response rates (odds ratio 1.21, 95% CI 1.01 to 1.44, P = 0.04) although we observed significant heterogeneity for this outcome across the trials. Where measured, acute toxicities such as alopecia, nausea and vomiting and leucopenia were more common with the addition of a drug.

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