Capecitabine-A "Permanent Mission" in Head and Neck Cancers "War Council"?

Capecitabine, an oral pro-drug that is metabolized to 5-FU, has been used in clinical practice for more than 20 years, being part of the therapeutic standard for digestive and breast cancers. The use of capecitabine has been evaluated in many trials including cases diagnosed in recurrent or metastatic settings. Induction regimens or a combination with radiation therapy were evaluated in head and neck cancers, but 5-FU still remained the fluoropyrimidine used as a part of the current therapeutic standard. Quantifications of levels or ratios for enzymes are involved in the capecitabine metabolism to 5-FU but are also involved in its conversion and elimination that may lead to discontinuation, dose reduction or escalation of treatment in order to obtain the best therapeutic ratio. These strategies based on biomarkers may be relevant in the context of the implementation of precision oncology. In particular for head and neck cancers, the identification of biomarkers to select possible cases of severe toxicity requiring discontinuation of treatment, including "multi-omics" approaches, evaluate not only serological biomarkers, but also miRNAs, imaging and radiomics which will ensure capecitabine a role in both induction and concomitant or even adjuvant and palliative settings. An approach including routine testing of dihydropyrimidine dehydrogenase (DPD) or even the thymidine phosphorylase (TP)/DPD ratio and the inclusion of miRNAs, imaging and radiomics parameters in multi-omics models will help implement "precision chemotherapy" in HNC, a concept supported by the importance of avoiding interruptions or treatment delays in this type of cancer. The chemosensitivity and prognostic features of HPV-OPC cancers open new horizons for the use of capecitabine in heavily pretreated metastatic cases. Vorinostat and lapatinib are agents that can be associated with capecitabine in future clinical trials to increase the therapeutic ratio.