A radical Chemoradiation schedule with hypofractionated radiotherapy plus capecitabine for esophageal cancer patients that are unfit for the standard chemoradiation; a phase II study

Rationale: This prospective study investigates the feasibility and toxicity of a hypo-fractionated radiation regime combined with an oral sensitizing drug (Capecitabine) in patients with a locally advanced esophageal tumor who are considered unfit for the standard chemoradiotherapy. Introduction: Technically irresectable or medically inoperable patients in a curable stage of disease of esophageal cancer are referred for curatively intended chemoradiation. The standard chemoradiation schedule consists of 50,4 Gy with 6x weekly Carboplatin and Paclitaxel. This schedule has a curative intent (3-years OS = 40%) but leads to grade III toxicity in about one third of the patients, with an excess in toxicity in older patients. This standard CRT regime is often considered too heavy for old or unfit patients. For patients considered not eligible for the standard chemoradiation, a palliative radiotherapy only schedule remains. The Dutch national radiation guideline suggests for unfit patients a hypo fractionated scheme of 50 Gy in 16 fractions, which is considered feasible in this patient group. However, radiation only for esophageal cancer should be considered as palliative. The combination of radiation with sensitizing chemotherapy has proven to change the intend from palliative to curative. Capecitabine, an oral drug which metabolizes in the body to the active drug 5-FU, is a well-known radiosensitizer, with a mild toxicity profile, which can be adapted quickly and easy according to the encountered toxicity. Primary question is whether this mild sensitizing drug combined with a high dose hypofractionated radiation regime to the esophageal region is feasible in this unfit patient group. Second question is whether this new schedule might lead to long term loco regional tumor control en thus eventually cure. Feasibility will be assessed as the number of patient completing the course. If feasible, and considered less toxic than the standard chemoradiaton regime, a national comparative study will be conducted between radiation with and without capecitabine. Objective: To investigate feasibility of a hypofractionated radiation schedule combined with daily Capecitabine for esophageal cancer patients considered unfit for standard chemoradiation Study design: A phase II prospective interventional drug study

a combination of 16 x 3.125 Gy plus twice daily capecitabine (825 mg\m2) is feasible for patients considered unfit for the standard radiochemotherapy (50,4 Gy + carboplatin and paclitaxel)

none

adding capecitabine to the standard radiation schedule