The Overall Efficacy and Outcomes of Metronomic Tegafur-Uracil Chemotherapy on Locally Advanced Head and Neck Squamous Cell Carcinoma: A Real-World Cohort Experience

Abstract

Metronomic chemotherapy inhibits tumor growth by continuous administration of lower-dose chemotherapy. Our study aimed to demonstrate the outcomes of metronomic chemotherapy with tegafur–uracil in locally advanced head and neck squamous cell carcinoma (LA HNSCC). This was a retrospective study including 240 patients with LA HNSCC. After standard treatment, 96 patients were further treated with metronomic tegafur-uracil, and 144 patients were not. No statistical differences were found between both groups with regard to sex, clinical stage, or primary treatment choice. There were more hypopharyngeal cancers and more patients with poor clinicopathological features, including lymphovascular invasion, extranodal extension, and positive margins in the tegafur–uracil group. The median follow-up duration was 31.16 months. Overall survival (OS) was not reached in the tegafur–uracil group and was 54.1 months in the control group (p = 0.008). The median disease-free survival (DFS) was 54.5 months in the tegafur–uracil group and 34.4 months in the control group (p = 0.03). Neither group reached distant metastasis-free survival (DMFS, p = 0.02). In patients with LA HNSCC, adding tegafur–uracil as metronomic chemotherapy after either curative surgery with adjuvant chemoradiotherapy or definitive concurrent chemoradiotherapy significantly improved the OS, DFS, and DMFS with tolerable adverse events.

Metronomic Chemotherapy in Oral Cancer: A Review

“…Metronomic chemotherapy (MC) utilizes lower doses of chemotherapeutic drugs than the MTD of conventional chemotherapy. It is administered at regular intervals without any long recovery phases between cycles, thereby maintaining a consistent drug level in the blood [6,[8][9][10].…”

“…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 ].…”

Shooting at Moving and Hidden Targets—Tumour Cell Plasticity and the Notch Signalling Pathway in Head and Neck Squamous Cell Carcinomas

“…The primary, initial treatment guidelines for HNSCC vary, according to the location of the tumour and stage of the disease, and can be improved with metronomic chemotherapy [ 61 ]. The mechanism of action for all “classic” chemotherapeutics is typically based on cytotoxicity, targeting generic, non-cancer specific processes such as mitosis and DNA damage/damage response.…”

Metronomic adjuvant chemotherapy evaluation in locally advanced head and neck cancers post radical chemoradiation – a randomised trial

“… 4 , 7 , 8 Multiple retrospective and prospective studies have suggested that adjuvant metronomic chemotherapy may improve outcomes in HNSCC. 9 , 10 , 11 , 12 , 13 In view of the encouraging data from palliative setting and small clinical data in the adjuvant setting we decided to test it in the adjuvant setting. Hence we did a phase 3 randomized study to assess whether adjuvant treatment with the metronomic combination of methotrexate and celecoxib leads to improvement in outcome in locally advanced head and neck cancers post radical chemoradiation.…”