Clinical overview of metronomic chemotherapy in breast cancer

Abstract

Over 15 years ago, low-dose metronomic chemotherapy was shown to induce disease control in patients with advanced-stage breast cancer with a lower incidence of adverse events compared with conventional maximum tolerated dose chemotherapy. Good response rates have been seen in heavily pre-treated patients for whom limited treatment options are available. Most patients prefer oral therapy and metronomic chemotherapy is a convenient alternative in patients with advanced-stage disease in which minimal toxicity and good tumour control are the overall aims of treatment. The addition of metronomic protocols to standard neoadjuvant chemotherapy regimens has produced promising pathological complete response rates. Ongoing trials including the SYSUCC-001 trial in patients with triple-negative breast cancer and the IBCSG 22-00 trial that is assessing a cyclophosphamide-methotrexate maintenance regimen after standard adjuvant therapy in hormone receptor-negative disease, will clarify the value of adding this approach to conventional therapies. The low cost associated with metronomic chemotherapy represents an opportunity for the utilization of this treatment option, especially in developing countries, and poses a challenge for the launch of large trials sponsored by industry. Using breast cancer as the principal example, we discuss the key clinical advances in this area, including new trial design, appropriate patient and end point selection, as well as the evolving rationale for metronomic chemotherapy combinations.

The efficacy and toxicity profile of metronomic chemotherapy for metastatic breast cancer: A meta-analysis

“…Munzone et al summarized some ongoing clinical trials and the forthcoming results may be helpful [2,15]. Meanwhile, according to the principles of precision medicine, prognosis factors such as vascular endothelial growth factor (VEGF), serum HER-2 and EGFR, endothelial nitric oxide synthase (eNOS), thrombospondin-1 (THBS-1), circulating endothelial cells (CECs), and gene polymorphism should be considered for patient selection to standardize MCT [18,26,28,32,43].…”

“…Another MCT study showed weekly paclitaxel dosing resulted in a higher complete response (CR) rate compared to a standard 3-week schedule [14]. A series of single-arm, phase II clinical trials involving the various types of chemotherapeutic agents used in MCT have been conducted [15]. However, the results of these research studies have been conflicting.…”

Tumor Evolution as a Therapeutic Target

“…In this model, intermittent doses (i.e., drug holidays) failed to control tumor growth (122). Indeed, low-dose maintenance regimens have long been evaluated in clinical practice (125); however, evidence showing the control of tumor evolution through metronomic approaches in patients is lacking. In this setting, measuring tumor evolution could offer additional criteria to assess the efficacy of complex regimens and possibly to model more effective sequences of induction and maintenance therapy for solid tumors.…”

Explorative Analysis of Low-Dose Metronomic Chemotherapy with Cyclophosphamide and Methotrexate in a Cohort of Metastatic Breast Cancer Patients

“…Many studies showed that LDMC used for palliation can achieve disease control and prolonged overall survival without severe side effects [7]. Over the last decade, clinicians have begun to consider introducing LDMC much earlier into the treatment plan [8,9]. In comparison with conventional chemotherapy, the lower doses of LDMC may induce fewer side effects [10,11,12,13], which may lead to a lower rate of discontinuation due to side effects such as myelosuppression [10].…”