Methotrexate, an attractive agent for palliation in head and neck cancers.

Dear Editor,

We would like to commend Chakraborty et al.[1] for reigniting interest in the use of methotrexate in palliative care in head and neck carcinomas. Palliation in head and neck region poses many problems; most of the patients are elderly with a multitude of comorbidities. Years of neglect, reluctance to give up smoking and decreased intake compounds the problem. Methotrexate has been one of the initial agents that have proven to be successful in the palliation of advanced malignancies of this region. Its low cost and availability increase its appeal in expanding its use in developing nations.

Two recent trials have studied methotrexate in palliative setting in head and neck carcinomas and deserve special mention.

In a phase III study, on 486 patients by Stewart et al.,[2] oral gefitinib, neither in a dose of 250 mg nor 500 mg was able to improve survival rates in recurrent squamous cell carcinoma of the head and neck. Though methotrexate was used in a dose of 40 mg/m2 weekly the adverse events between the two schedules were not different.

The other study GORTEC 9803 was closed early, and only 57 patients were included.[3] The intensive schedule of reirradiation given concurrently with hydroxyurea and fluorouracil was not found to be better than methotrexate in terms of survival rate.

Thus, methotrexate has compared well with contemporary palliative treatments on randomized comparisons. This is further established in the study by Chakraborty et al.[1]

The oral bioavailability of methotrexate is good, and if the patient is having oral intake, this route would save the already infirm patients the relatively painful intravenous route. Thus, it would also be a much cheaper alternative to gefitinib.

The point of concern is that common medications need to be monitored during methotrexate therapy. Pain is a common complaint in advanced head and neck malignancy, and non-steroidal anti-inflammatory drug are commonly prescribed to such patients. Many fatal interactions have been described on concomitant use.[4] Many other common drugs like folic acid, proton pump inhibitors, etc., have effects on either the toxicity or the effectiveness of this drug.[5] Thus, due caution in use with methotrexate is needed.

To conclude, the options like methotrexate need to be explored further. Low-income groups would definitely benefit with such approaches.