In patients with non-resectable head and neck cancer concomitant chemoradiotherapy is increasingly used, especially in cases of oropharyngeal and hypopharyngeal tumours. Most chemoradiotherapy regimens contain cisplatin as a single agent or in combination with fluorouracil. However, not all patients are fit enough for a cisplatin-containing regimen or they refuse hospital admission. Raltitrexed is a specific thymidylate synthase inhibitor that has been studied as a radiosensitiser in rectal cancer. Raltitrexed can be administered easily in an outpatient setting and has few short-term side-effects. We studied raltitrexed at escalating doses combined with standard radiotherapy in advanced head and neck cancer patients. Seventeen patients with locally advanced head and neck cancer were enrolled in the study. Raltitrexed was administered at dose levels of 1.5, 2.0, 2.5 and 3.0 mg/m 2 intravenously (i.v.), once every 3 weeks, for two doses. Radiotherapy consisted of 70 Gy given over 7 weeks in five fractions of 2 Gy per week. In general, treatment was well tolerated. Toxicity consisted mainly of locoregional radiation toxicity (mucositis and skin toxicity). Systemic dose-limiting toxicity (DLT), complicated febrile neutropenia, was observed at 3.0 mg/m 2 in two of four patients. The dose of 2.5 mg/m 2 was extended thereafter with 3 additional patients without major toxicity. Radiotherapy had to be interrupted in one patient. Five patients had a clinical complete response (CR) and eleven a partial response (PR) six weeks after the last fraction of radiotherapy. Twelve out of 17 patients remained free of locoregional recurrence after a median follow-up of 24 + months (range 3-60+ months). Raltitrexed, at a dose of 2.5 mg/m 2 given twice 3 weeks apart, can be administered in combination with 70 Gy of radiotherapy in locally advanced head and neck cancer patients with a manageable tolerability profile. The clinical results and convenience of the schedule make raltitrexed an attractive drug to explore further in patients considered unfit for cisplatin-containing chemoradiation regimens.

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doi.org/10.1016/j.ejca.2004.09.022, hdl.handle.net/1765/65697
European Journal of Cancer
Department of Otorhinolaryngology

Planting, A.S.Th, de Jonge, M.J.A, Jansen, P.P, Kerrebijn, J.D.F, Smith, M, & Verweij, J. (2005). Phase I study of concomitant chemoradiation with raltitrexed in locally advanced head and neck cancer. European Journal of Cancer, 41(1), 93–97. doi:10.1016/j.ejca.2004.09.022