ORAL METHOTREXATE AS SECOND LINE CHEMOTHERAPY IN PLATINUM-REFRACTORY OR RELAPSED SQUAMOUS CELL CARCINOMA OF THE HEAD AND NECK
Purpose: Platinum-refractory or relapsed squamous cell carcinoma of the head and neck (SCCHN) is considered to have poor prognosis. Although cetuximab is currently recommended as category 1 in this group of patients, the use of it is hampered in low- and middle-income countries (LMICs) like Pakistan due to nancial constraints. Further, majority of the population of these countries is unable to tolerate toxicity related to other intravenous chemotherapeutic agents due to lower socioeconomic background with poor nutrition status. The aim of this study is to evaluate the response rate and toxicity of oral methotrexate (MTX) in platinum-refractory or relapsed SCCHN.
Methods: Between June 2008 and December 2012, 71 patients received palliative oral MTX either due to recurrent or persistent disease. With a median age of 51 years (range 22–75), there were 68% of males and 32% of females. Site distribution was as following; oral cavity 58%, nasopharynx 25%, hypopharynx 7%, paranasal sinuses 6%, larynx 3%, Oropharynx 1%. Patterns of recurrence; local 32%, regional 07%, loco regional 10%, distant 15% and persistent disease in 36% of the patients. All the patients received oral MTX 10 mg once a day, 4 days a week. To contain the possible side effects associated with MTX, folinic acid 15 mg per oral every 6 hourly on day 5 was prescribed. Response assessment was done on two monthly basis. Response, toxicity, mean response time and mean time to progression were determined.
Results: Response to MTX was as following; complete response 3%, partial response 4%, stable disease 11% and progressive disease in 82% of the patients respectively. Toxicity related to oral MTX includes neutropenia Grade III in 1% while mucositis Grade III in 10% of the patients, respectively. None of the patient had Grade IV mucositis or haematological toxicity. Treatment was stopped in 13% of the patients due to poor compliance. Mean response time was 4 months (range 1 – 20) and mean time to progression was 5 months (range 1–23).
Conclusion: Oral MTX is a simple, cost-effective and well-tolerated regimen to be used on outpatient basis for palliation in platinum refractory or relapsed SCCHN in LMICs and debilitated patients. This treatment merits further evaluation in large-scale clinical trials.
Key words: Oral methotrexate, platinum refractory, relapsed squamous cell carcinoma of head and neck
Stewart BW, Kleihues PE. World Cancer Report. Lyon, France: International Agency for Research on Cancer Press; 2003.
Lag R, Melbert D, Krapcho M. SEER Cancer Statistics Review, 1975-2004. Bethesda, MD: National Cancer Institute; 2006.
Vermorken JB, Mesia R, Rivera F, et al. Platinum-based chemotherapy plus cetuximab in head and neck cancer. N Engl J Med 2008;359:1116-27.
Forastiere AA, Metch B, Schuller DE, et al. Randomized comparison of cisplatin plus uorouracil and carboplatin plus fluorouracil versus methotrexate in advanced squamous-cell carcinoma of the head and neck: A southwest oncology group study. J Clin Oncol 1992;10:1245-51.
Cohen EE, Lingen MW, Vokes EE. The expanding role of systemic therapy in head and neck cancer. J Clin Oncol 2004;22:1743-52.
Jacobs C, Lyman G, Velez-García E, et al. A phase III randomized study comparing cisplatin and uorouracil as single agents and in combination for advanced squamous cell carcinoma of the head and neck. J Clin Oncol 1992;10:257-63.
Burtness B, Goldwasser MA, Flood W, et al. Phase III randomized trial of cisplatin plus placebo compared with cisplatin plus cetuximab in metastatic/recurrent head and neck cancer: An eastern cooperative oncology group study. J Clin Oncol 2005;23:8646-54.
Colevas AD. Chemotherapy options for patients with metastatic or recurrent squamous cell carcinoma of the head and neck. J Clin Oncol 2006;24:2644-52.
Vermorken JB, Specenier P. Optimal treatment for recurrent/ metastatic head and neck cancer. Ann Oncol 2010;21 Suppl 7:7252-61.
Price KA, Cohen EE. Current treatment options for metastatic head and neck cancer. Curr Treat Options Oncol 2012;13:35-46.
Vermorken J, Hitt R, Geoffrois L, et al. Cetuximab plus platinum-based therapy first-line in recurrent and/or metastatic (R/M) squamous cell carcinoma of the head and neck (SCCHN): Ef cacy and safety results of a randomized phase IIItrial (EXTREME). Eur J Cancer 2007;5:324.
Tejani MA, Cohen RB, Mehra R. The contribution of cetuximab in the treatment of recurrent and/or metastatic head and neck cancer. Biologics 2010;4:173-85.
Rivera F, García-Castaño A, Vega N, et al. Cetuximab in metastatic or recurrent head and neck cancer: The EXTREME trial. Expert Rev Anticancer Ther 2009;9:1421-8.
LeonX,HittR,ConstenlaM,etal.Aretrospectiveanalysis of the outcome of patients (pts) with recurrent or metastatic squamous cell carcinoma of the head and neck (R and M SCCHN) who are progressing while on a platinum- based palliative chemotherapy. Proc Am Soc Clin Oncol 2003;22:502.
HerbstRS,ArquetteM,ShinDM,etal.PhaseIImulticenter study of the epidermal growth factor receptor antibody cetuximab and cisplatin for recurrent and refractory squamous cell carcinoma of the head and neck. J Clin Oncol 2005;23:5578-87.
Baselga J, Trigo JM, Bourhis J, et al. Phase II multicenter study of the antiepidermal growth factor receptor monoclonal antibody cetuximab in combination with platinum-based chemotherapy in patients with platinum-refractory metastatic and/or recurrent squamous cell carcinoma of the head and neck. J Clin Oncol 2005;23:5568-77.
Yokota T, Onozawa Y, Boku N, et al. S-1 monotherapy for recurrent or metastatic squamous cell carcinoma of the head and neck after progression on platinum-based chemotherapy. Jpn J Clin Oncol 2011;41:1351-7.
Murthy V, Gupta T, Agarwal JP, et al. Cautious optimism in advanced incurable head neck cancer. Radiother Oncol 2008;89:123-4.
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