Treating metastatic breast cancer with one chemotherapy medicine at a time (monotherapy) is as effective as using two or more chemotherapy medicines at the same time (combination chemotherapy), according to the study reviewed here. Monotherapy also was less likely to cause side effects and any side effects were likely to be less severe compared to combination chemotherapy.
Metastatic breast cancer is breast cancer that has spread to other parts of the body. Metastatic breast cancer is considered advanced-stage cancer. Chemotherapy is an important part of the treatment plan for metastatic breast cancers and there are a number of chemotherapy medicines that can be used. In some cases one chemotherapy medicine at a time is used. If one medicine stops working or causes severe side effects, there's usually another medicine that can be used.
Some doctors think that combination chemotherapy is better than monotherapy because combination chemotherapy attacks the cancer cells in more than one way. If some of the cancer cells become resistant to one of the combination chemotherapy medicines, the hope in that one of the other medicines in the combination will kill the cells. Still, most chemotherapy medicines may cause bothersome side effects that can be very serious. Each medicine in combination chemotherapy has its own set of potential side effects. So it's not surprising that side effects from combination chemotherapy may be worse than those caused by monotherapy.
In this study, researchers looked at the results of eight studies comparing monotherapy to combination chemotherapy to treat metastatic breast cancer. In six of the studies, women who got monotherapy did just as well as women who got combination chemotherapy. The other two studies had conflicting results. One found that women who got monotherapy did better than women who got combination chemotherapy. The other study found that women who got combination chemotherapy did better than women who got monotherapy. All of the studies found that side effects were more likely and more severe with combination chemotherapy.
Based on their analysis, the researchers concluded that monotherapy generally should be the first type of chemotherapy given to treat metastatic breast cancer.
If you've been diagnosed with metastatic breast cancer, your doctor will consider:
Most women with metastatic breast cancer should receive sequential monotherapy rather than combination chemotherapy, a European breast cancer task force concluded.
The recommendation came with several caveats, though.
Evidence of rapid clinical progression, life-threatening visceral metastases, or the need for rapid symptom or disease control may warrant consideration of combination therapy, according to a report from the European School of Oncology Metastatic Breast Cancer Task force.
Moreover, members of the task force acknowledged that combination therapy improves response rate and time to progression compared with sequential therapy, but at a cost of increased toxicity.
However, clinical trials and meta-analyses have failed to provide data adequate to draw definitive conclusions about quality of life and overall survival.
"Because metastatic breast cancer is an incurable disease and the main aim of treatment is palliation, quality of life and overall survival should be the ultimate endpoints against which any systemic therapy is evaluated," Fatima Cardoso, MD, of the Jules Bordet Institute in Brussels, and colleagues said online in the Journal of the National Cancer Institute.
"As a result, a properly conducted multi-institutional clinical trial with predefined therapy following progression in both the combination and sequential arms is needed."
"Moreover, urgent research is required on the development and evaluation of supportive interventions that might ameliorate the toxic effects and side effects associated with the otherwise most efficacious chemotherapies," the authors added.
Weighing all the evidence, the task force found both strategies acceptable as first-line therapy for metastatic breast cancer but called sequential monotherapy the preferred strategy.
Several guidelines have been developed for adjuvant treatment of breast cancer. In contrast, no consensus exists about management of metastatic breast cancer.
Acknowledging the lack of clinical direction, the European School of Oncology and the European Breast Cancer Conference created a task force to develop recommendations for management of metastatic breast cancer.
The task force reviewed literature on a variety of management strategies, including:
In general, the studies demonstrated advantages for combination chemotherapy with respect to response rate and time to progression and occasionally overall survival. But some of the differences were small, and the results did not consistently show statistically significant improvement with combination therapy.
Similarly, meta-analyses have demonstrated significant outcome advantages for combination therapy versus sequential monotherapy, but the task force found flaws in design or analytic methods. Examples included biases introduced by inclusion of trials evaluating outdated chemotherapy regimens and inadequate assessment of sequential treatment.
Of eight randomized trials that appropriately addressed issues related to crossover and sequential therapy, six showed no difference between the two treatment strategies. The other two yielded conflicting results, one favoring sequential therapy and the other combination therapy.
In all of the studies, combination therapy was associated with increased toxicity.
"It appears that combination therapy is associated with improved response rate and time to progression compared with sequential therapy with greater expected treatment-related toxicity," the task force members said.
"Unfortunately, it is difficult to draw definitive conclusions regarding the impact of therapy on overall survival and quality of life; the latter, in part, because many trials do not report the incidence of low-grade toxic effects that may be most relevant to patients with metastatic disease."
In the absence of clear guidance regarding clinical decision-making in metastatic breast cancer, "both combination and sequential single-agent chemotherapy are reasonable options as first-line systemic therapy," they added.
Although either strategy might be appropriate, the task force members recommended sequential monotherapy as the "preferred choice."
The authors disclosed no relationships.
Primary source: Journal of the National Cancer Institute Source reference: Cardoso F, et al "International guidelines for management of metastatic breast cancer: combination vs sequential single-agent chemotherapy" J Natl Cancer Inst 2009; 101: 1174-81.
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