Metronomic Chemotherapy in Cancer Treatment

Metronomic chemotherapy is defined by the continuous or frequent administration of chemotherapeutic agents at substantially lower doses than those used in conventional maximum tolerated dose protocols, without prolonged drug-free intervals. Originally conceived to limit toxicity, this approach has revealed a multifaceted mechanism of action encompassing antiangiogenic effects, direct cytotoxicity, immunomodulation and metabolic reprogramming within the tumour microenvironment. By targeting rapidly proliferating endothelial cells and by normalising tumour vasculature, metronomic regimens suppress angiogenesis more effectively than intermittent high-dose schedules. Concurrently, low-dose administration shapes the host immune response by reducing regulatory T-cell populations and enhancing effector lymphocyte activity. Clinically, metronomic chemotherapy has evolved from salvage therapy for refractory and metastatic disease to adjuvant and maintenance settings for high-risk patients, with several late-phase trials demonstrating disease control in breast, lung, colorectal and paediatric malignancies. The reduced toxicity profile facilitates prolonged treatment courses, improves quality of life and offers a cost-effective alternative in resource-limited environments. Ongoing research seeks to optimise drug selection, scheduling and combination with targeted agents or immunotherapies, and to identify predictive biomarkers for individualised metronomic regimens.

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Metronomic Chemotherapy in Cancer Treatment publication trend

The graph below shows the total number of articles in metronomic chemotherapy in cancer treatment across all publications each year (not limited to Nature Index journals).

Technical terms

Antiangiogenesis: Inhibition of new blood vessel formation that supplies nutrients to tumours, achieved by sustained low-dose chemotherapy targeting endothelial cells.

Immunomodulation: Alteration of the immune system’s balance, often by reducing regulatory T-cells and enhancing cytotoxic lymphocyte activity under metronomic dosing.

Maximum Tolerated Dose (MTD): The highest drug dose at which a predefined level of toxicity is acceptable; traditional chemotherapy is administered at or near the MTD.

Maintenance Therapy: Prolonged administration of therapeutic agents at low or moderate intensity to sustain disease control after initial response.

Tumour Microenvironment: The cellular and non-cellular milieu surrounding cancer cells, including stromal cells, immune cells and vasculature, which influences tumour growth and treatment response.

References

1. Metronomic chemotherapy in cancer treatment: new wine in an old bottle. Theranostics (2024).
2. Phase II randomized trial comparing metronomic anthracycline-containing chemotherapy versus standard schedule in untreated HER2 negative advanced breast cancer: activity and quality of life results of the GOIM 21003 trial. The Breast (2024).
3. Metronomic Chemotherapy in Elderly Patients. Current Oncology Reports (2024).