Phase I/II Study of Palliative Triple Metronomic Chemotherapy in Platinum-Refractory/Early-Failure Oral Cancer

Abstract

PURPOSE Platinum-resistant oral cancer has a dismal outcome with limited treatment options. We conducted a phase I/II study to identify the optimal biologic dose (OBD) of methotrexate when given along with erlotinib and celecoxib and to assess the efficacy of this three-drug regimen in advanced oral cancer. METHODS Patients with platinum-resistant or early-failure squamous cell carcinoma of the oral cavity were eligible for this study. They were orally administered erlotinib 150 mg once per day, celecoxib 200 mg twice per day, and methotrexate per week. The primary end point of phase I was to determine the OBD of methotrexate, and that of phase II was to determine the 3-month progression-free survival. The OBD of methotrexate was determined on the basis of the clinical benefit rate at 2 months and circulating endothelial cell level at day 8, using a de-escalation model. Pharmacokinetic evaluation was performed during phase I. Phase II consisted of an expansion cohort of 76 patients. RESULTS Fifteen patients were recruited in phase I, and 9 mg/m2 methotrexate was identified as the OBD. A total of 91 patients were recruited, and the median follow-up was 6.8 months (range, 0 to 16.8 months). The 3-month progression-free survival rate was 71.1% (95% CI, 60.5% to 79.3%), the 6-month overall survival rate was 61.2% (95% CI, 49.2% to 67.8%), and the response rate was 42.9% (95% CI, 33.2% to 53.1%; n = 39). The mean Functional Assessment of Cancer Therapy-Head and Neck Trial Outcome Index score at day 8 was improved by 6.1 units (standard deviation, 13.6 units) and was maintained around this magnitude ( P = .001). CONCLUSION Triple oral metronomic chemotherapy with erlotinib, methotrexate, and celecoxib is efficacious in platinum-refractory oral cavity cancers and represents a new therapeutic option in patients with poor prognosis.

Low-cost oral metronomic chemotherapy versus intravenous cisplatin in patients with recurrent, metastatic, inoperable head and neck carcinoma: an open-label, parallel-group, non-inferiority, randomised, phase 3 trial

“…1,2 Palliative systemic therapy is used to treat recurrent, relapsed, or newly diagnosed head and neck cancers that are not amenable to any localised therapy upfront. [3][4][5] The current standard options for palliative systemic therapy, according to the US National Compre hensive Cancer Network (NCCN) guidelines, 6 are the EXTREME trial 7 regimen (cisplatin, fluorouracil, and cetuximab) and the KEYNOTE-048 trial 8 regimen (pembrolizumab with or without cisplatin and fluorouracil). However, the use of these regimens is low (less than 1-3%) in LMICs because of their cost.…”

Recurrent cervical cancer treated with palliative chemotherapy: real-world outcome

“…Further data are needed regarding the outcomes and ideal protocols of OMC with pharmacokinetics in this population, as we have in head and neck cancer patients [26]. However, till such data become available, the use of well-tolerated simple CT protocols may form the cornerstone for effective palliation of such patients.…”

Widely disseminated metastatic Ewing sarcoma: Sustained, complete metabolic response to first‐line oral metronomic chemotherapy

“…However, careful patient selection is a vital factor for determining the success of any treatment; as of now, we do not have enough data to predict responses in patients. Further prospective trials focusing on optimal doses and circulating biomarkers are required to optimize the use of OMCT in different cancer subtypes, as was reported in head and neck cancers 25 . With such data, the indications and the use of OMCT may be widened and thus in this era of precision medicine, standardized OMCT protocols may be integrated into the mainstream of oncology both in LMICs and high income countries.…”