Oral cancer, the sixth most common cancer worldwide, remains the most prevalent. Despite recent advancements in surgery and radiotherapy, the overall cure rate is achieved in less than 50% of patients. In contrast to many other cancers, distant metastasis is rarely present at diagnosis, but due to improved local control, the incidence of systemic spread is rapidly increasing. Most combination radiation-chemotherapy regimens have been developed empirically by administering drugs that exhibited some activity against the targeted tumors, using a dosage and timing sequence known to be tolerable in a single-modality therapy setting. Likewise, adjuvant chemotherapy following surgical resection did not show a survival benefit.