Patil VM, et al. - Via performing a phase 1/2 study, researchers sought to determine the optimal biologic dose (OBD) of methotrexate when given along with erlotinib and celecoxib and examined the effectiveness of this three-drug regimen in patients with platinum-resistant or early-failure squamous cell carcinoma of the oral cavity. Patients were provided erlotinib 150 mg once per day, celecoxib 200 mg twice per day, and methotrexate per week. Of phase 1, the primary endpoint was to define the OBD of methotrexate, and of phase 2, the primary endpoint was to determine the 3-month progression-free survival. In phase 1, 15 patients were recruited, and the identified OBD was 9 mg/m² for methotrexate. They noted 3-month progression-free survival rate of 71.1%, the 6-month overall survival rate of 61.2%, and the response rate of 42.9%. An improvement in the mean Functional Assessment of Cancer Therapy-Head and Neck Trial Outcome Index score at day 8 by 6.1 units was reported (standard deviation, 13.6 units) and it was maintained around this magnitude. Outcomes support the efficacy of triple oral metronomic chemotherapy with erlotinib, methotrexate, and celecoxib in platinum-refractory oral cavity cancers and describe it as a new therapeutic option in patients with poor prognosis.