Three-Drug Palliative Chemotherapy Regimen Shows Promise for Advanced Oral Cancer

The methotrexate-based regimen proved to lengthen survival and improve quality of life among patients with platinum-resistant oral cancer.

A new triplet regimen, serving as palliative chemotherapy and comprised of erlotinib (Tarceva), celecoxib (Celebrex), and methotrexate improved survival and quality of life among patients with platinum-resistant oral cancer, according to phase I/II study findings published in the Journal of Clinical Oncology.

Platinum-resistant oral cancer leaves patients with few options. Among the worst cases, resistance to treatment develops within a month – and for those, the median survival is just 3 to 5 months beyond that, according to the literature. 

In phase I of the study, investigators identified the optimal biologic dose of methotrexate when given along with erlotinib and celecoxib in 15 patients, which was calculated by assessing the clinical benefit rate at the 2-month mark, and the counts of circulating endothelial cells at the day-8 mark.

With this, the investigators determined that 9 mg/mwas the optimal biologic dose. 

In phase II of the study, investigators then aimed to assess the efficacy of the 3-drug regimen in 91 patients, include 76 enrolled as part of the expansion cohort, with advanced oral cancer.

After a median follow-up of 6.8 months (range, 0 to 16.8 months), the 3-month progression-free survival (PFS) rate was 71.1% (95% CI, 60.5%-79.3%), the 6-month overall survival rate was 61.2% (95% CI, 49.2%-67.8%), and the response rate was 42.9% (95% CI, 33.2%-53.1%) – including 39 complete responses.

Regarding quality of life, 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). 

“The basic principle of any palliative therapy is to provide symptomatic relief and improve survival. Improvement in the quality of life rarely has been demonstrated with the use of palliative chemotherapy in head and neck cancer,” the investigators wrote. “The improvement of (Trial Outcome Index) scores in the current study suggests that this regimen provides symptom relief and thus improves the quality of life.”

“The combination of erlotinib, (methotrexate), and celecoxib in platinum-insensitive oral cancer results in promising response rates, progression-free survival, and overall survival,” the investigators wrote. “Its activity needs to be confirmed in a phase III randomized study.”

The investigators acknowledged the study was limited from being conducted in a single cancer center, and that the Indian population of oral cancer is predominantly associated with chewing tobacco, as opposed to most cases in the West.

Ultimately, the 3-drug regimen proves to have a net benefit for the toughest oral cancers which are stubbornly resistant to treatment, the investigators concluded.

“…The (response rates) and median PFS produced by the triple oral metronomic chemotherapy regimen, accompanied with a low rate of adverse events, is exciting and suggests its potential as an alternative treatment,” they added.


Patil VM, Noronha V, Joshi A, et al. Phase I/II Study of Palliative Triple Metronomic Chemotherapy in Platinum-Refractory/Early-Failure Oral Cancer. J Clin Oncol. doi:10.1200/JCO.19.01076.