Metronomic Therapy in Oral Squamous Cell Carcinoma

Abstract

Metronomic therapy is characterized by drug administration in a low-dose, repeated, and regular manner without prolonged drug-free interval. The two main anticancer mechanisms of metronomic therapy are antiangiogenesis and immunomodulation, which have been demonstrated in several delicate in vitro and in vivo experiments. In contrast to the traditional maximum tolerated dose (MTD) dosing of chemotherapy, metronomic therapy possesses comparative efficacy but greatlydecreases the incidence and severity of treatment side-effects. Clinical trials of metronomic anticancer treatment have revealed promising results in a variety cancer types and specific patient populations such as the elderly and pediatric malignancies. Oral cavity squamous cell carcinoma (OCSCC) is an important health issue in many areas around the world. Long-term survival is about 50% in locally advanced disease despite having high-intensity treatment combined surgery, radiotherapy, and chemotherapy. In this article, we review and summarize the essence of metronomic therapy and focus on its applications in OCSCC treatment.

Metronomic Chemotherapy in Oral Cancer: A Review

“…It was given as targeted therapy, vascular disrupting agents, and non-cytotoxic agents. It is either given as adjuvant or maintenance therapy immediately after curative surgery or as a mode of palliative therapy in recurrent or metastatic tumors [ 5 ]. MC is administered continuously until one of the following outcomes: surgical therapy for advanced cancer cases, clinical progression in cases with metastasis, side effects are unbearable, or fatal complications occur [ 6 ].…”

“…However, treatment with MTD is associated with systemic toxicity and has to maintain drug-free periods of three to four weeks to permit patient recovery. Genomic evolution of cancer cells can induce platinum resistance, which is also a worrisome factor [ 5 ].…”

“…Novel therapeutic strategies like oral metronomic therapy are being used to improve patient outcomes for several malignancies [ 5 , 6 , 7 ]. Low-dose, repetitive, regular medication delivery without extended drug-free intervals is the hallmark of metronomic therapy [ 5 ].…”

“…Novel therapeutic strategies like oral metronomic therapy are being used to improve patient outcomes for several malignancies [ 5 , 6 , 7 ]. Low-dose, repetitive, regular medication delivery without extended drug-free intervals is the hallmark of metronomic therapy [ 5 ]. Yeh et al have reported the antitumor effects of tegafur-uracil as a metronomic agent in advanced oral cancer and nasopharyngeal carcinoma [ 8 , 9 ].…”

Cisplatin for cancer therapy and overcoming chemoresistance

“…Glutathione-responsive prodrugs such as glutathione tripeptide are widely used for having enhanced cytoplasmic drug release in tumours and a double or triple-fold increase in the intracellular accumulation compared to the tumour extracellular environment [ 93 , 94 ]. Metronomic therapy consists of delivering fractionated dosages of a highly toxic drug for an uninterrupted duration to maintain a low cytotoxicity profile while exposing the patients to a continuous regimen of chemotherapy [ 95 , 96 ]. It has inhibited tumour neovascularisation, angiogenesis, and endothelial cell proliferation also with immunogenic modulation of tumour suppression by presenting neoantigens and increasing programmed tumour cell death [ 97 ].…”