Selumetinib Ups Radioiodine Uptake in Thyroid Cancer
Increases radioiodine uptake and retention in patients with radioiodine-refractory disease
WEDNESDAY, Feb. 13 (HealthDay News) -- The mitogen-activated protein kinase (MAPK) kinase (MEK) 1 and MEK2 inhibitor selumetinib generates clinically meaningful increases in iodine uptake and retention in patients with radioiodine-refractory thyroid cancer, according to a study published in the Feb. 14 issue of the New England Journal of Medicine.
Alan L. Ho, M.D., Ph.D., from the Memorial Sloan-Kettering Cancer Center in New York City, and colleagues treated 20 patients (median age 81 years; 11 men) with selumetinib (75 mg twice daily). Dosimetry with iodine-124 positron-emission tomography (PET) was performed following stimulation with thyrotropin alfa, before and after four weeks of treatment with selumetinib. The second PET study was used to indicate whether therapeutic radioiodine could be administered to metastatic lesions while the patient was receiving selumetinib.
The researchers found that selumetinib treatment correlated with increased uptake of iodine-124 in 12 of the 20 patients (four of nine patients with BRAF mutations and all five patients with NRAS mutations). All five patients with NRAS mutations as well as three others reached the dosimetry threshold for radioiodine therapy. Five of the eight patients treated with radioiodine had confirmed partial responses and three had stable disease. Decreases in serum thyroglobulin levels (mean reduction, 89 percent) were seen in all patients. No toxic effects of grade 3 or higher were attributable to selumetinib.
"These results provide a proof of principle that MEK inhibitors can induce iodine uptake and retention in thyroid tumors," the authors write.
The trial was partially funded by AstraZeneca, which owns the licensing rights to selumetinib, and Genzyme. The iodine-124 PET studies were partially supported by In-Vivo Cellular and Molecular Imaging Center.