Study determines safe dose for the HDAC inhibitor in patients with gastrointestinal cancer-- Jeff Muise
Wednesday, April 7, 2010 (Last Updated: 04/08/2010)
WEDNESDAY, April 7 (HealthDay News) -- The histone deacetylase (HDAC) inhibitor vorinostat is safe to use in combination with short-term palliative radiotherapy for patients with gastrointestinal cancer, according to a study published online April 7 in The Lancet Oncology.
Anne Hansen Ree, M.D., of the Norwegian Radium Hospital in Oslo, and colleagues administered oral vorinostat to 17 patients with carcinoma, who were scheduled to receive pelvic radiation to 30 Gy in 3 Gy daily fractions over two weeks. The patients were medicated once daily, three hours before each radiotherapy session, at varied dose levels: 100, 200, 300 and 400 mg.
The researchers found that, among the 16 patients completing the study (one patient withdrew), most adverse events were grades 1 or 2, with fatigue and gastrointestinal events common to all patients. Grade 3 events included fatigue (five patients), acneiform rash (one), anorexia (three), diarrhea (two), hyponatraemia (one) and hypokalaemia (one). Dose-limiting toxicities occurred at the 300 mg dose in one of six patients (fatigue and anorexia), and at the 400 mg dose in two of six patients (diarrhea, fatigue, anorexia, hyponatraemia and hypokalaemia), suggesting a maximum daily dose of 300 mg. The researchers observed histone hyperacetylation, indicating biological activity of vorinostat.
"Vorinostat can be safely combined with short-term pelvic palliative radiotherapy. This study highlights the potential use of HDAC inhibitors with radiation, and suggests investigation of vorinostat in long-term curative pelvic radiotherapy -- e.g., as a component of preoperative chemoradiotherapy for rectal cancer," the authors write.
The study was funded in part by Merck & Company Inc., which markets vorinostat.
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