metronomic

Metronomic refers to a dosing approach in cancer therapy characterized by the frequent, regular administration of chemotherapy at relatively low doses with minimal or no prolonged drug-free breaks. The term evokes the steady rhythm of a metronome, and the regimen aims to maintain continuous, low-level anti-tumor pressure while reducing peak-dose toxicity compared with conventional high-dose schedules.

Mechanisms and rationale are central to metronomic chemotherapy. The strategy is thought to exert anti-tumor effects largely through anti-angiogenic activities, by inhibiting endothelial cell proliferation and disrupting tumor blood vessel formation, as well as by altering the tumor microenvironment. In some settings it may also modulate the immune response, such as reducing regulatory T cells and enhancing cytotoxic activity. Common agents used in metronomic regimens include oral cyclophosphamide, methotrexate, capecitabine, vinorelbine, temozolomide, among others, delivered on daily or short-interval schedules.

History and development note that the approach emerged in the late 1990s and early 2000s, with pivotal work by researchers including Judah Folkman and Judah Kerbel, who highlighted that continuous, low-dose strategies could suppress tumor growth via anti-angiogenic mechanisms and potentially overcome resistance to maximum-tolerated-dose regimens.

Clinical status and applications vary. Metronomic chemotherapy has been studied in multiple cancer types, including breast cancer, neuroblastoma, glioblastoma, and ovarian cancer, often in advanced disease, for maintenance therapy, or in combination with targeted therapies or immunotherapy. Evidence ranges from preclinical models to phase II trials, and results are heterogeneous, so it is not universally adopted as a replacement for conventional regimens.