Nightly dosing of regorafenib.

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549 Background: Fatigue and anorexia are major side effects in the use of regorafenib. These effects are compounded in patients with metastatic colon cancer to the liver. Finding a good fit for this agent has been difficult in patients when used in third and fourth line treatments. Our clinic has treated 21 patients with this agent. Methods: After the first four patients’s experienced extreme fatigue and anorexia at the recommended starting dose of 160mg daily, it was decided to start at a 21 day dose of 120mg. Even at this starting dose, it was necessary to dose deescalate. Ten patients were treated at the 120 mg daily dose and escalated 160 mg daily if tolerated. The agent was given at night to take advantage of the sleep period and the diurnal variation in adrenal gland function. No patient was treated with oral corticosteroids. Results: Two patients previously treated and responders were retreated after they decided they would give the agent a second opportunity. One of these patients, on day two of receiving the agent, developed a severe rash and the treatment was stopped. One patient received the agent for one week before he decided to stop, but was experiencing no side effects. Eight patients were eligible for evaluation. All patients had metastatic disease to the liver. Six were treated for at least two months and two were treated only for one month. All therapy was discontinued because of progression of disease. Fatigue and anorexia were evaluated by a change in their ECOG performance status, fatigue criteria and weight change. ECOG performance status of the patients was, ECOG 1, one patient, ECOG 2, six patients, ECOG 3, one patient. The evaluation was done before, during and after each monthly treatment. No patient had a greater than 5% weight loss. Four patients had Grade 1 fatigue, (fatigue relieved by resting). Six of the eight patients were escalated to 160mg daily after two weeks. Conclusions: Although this is a small sample study, it appears that night time dosing may be effective in helping a patient to achieve maximum benefit of regorafenib therapy. This study did not address the changes in absorption caused by a light fat free meal taken at night, and does not take into consideration the possible change in half-life of the agent when taken at night.