Metronomic Chemotherapy in Breast Cancer as a Strategy to Deliver More Sustainable and Less Toxic Treatments: Time to Debunk the Myth?

Breast cancer is the most commonly diagnosed cancer in women, worldwide. With the increasing burden of breast cancer, the search for more tolerable and sustainable treatments is required, to result in broader access to cancer treatments. Metronomic chemotherapy defines the use of chemotherapy agents based on low-dose, continuous regimens, as opposed to traditional treatments administered for limited intervals, at higher dose. The use of metronomic chemotherapies has been envisioned often as a way to reduce toxicity while maintaining similar efficacy, and result in reduced health system resource utilization, while tailoring some special populations' needs, such as the older adults with cancer. In our review, we provide a revision of the data available on the use of metronomic chemotherapy in breast cancer, as stratified per setting of use and subtypes of diseases. Clinical trials evaluating head-to-head metronomic and nonmetronomic schedules of chemotherapies broadly failed to meet their endpoints of noninferiority and/or superiority in term of safety, showing more often similar burden of adverse effect. Efficacy was also usually comparable. Data on financial implications appeared limited, and not conclusive of economic and health system benefits with the use of metronomic schedules. Our review of the evidence suggests that broad implementation of metronomic chemotherapy to enhance sustainability and safety may be not appropriate in all settings, as data for the optimized use are still warranted. The use of metronomic chemotherapy in breast cancer as a mean to improve tolerability, reduce treatment-related complications and associate costs and enhance sustainability of cancer treatments should not be pursued as an ultimate solution, in all settings of breast cancer treatment. Standard treatments having robustly proved to improve patient outcomes are to be prioritised for first, unless data suggest otherwise with these regimens.