A phase II trial of imatinib therapy for metastatic medullary thyroid carcinoma.

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de Groot JW, Zonnenberg BA, van Ufford-Mannesse PQ, de Vries MM, Links TP, Lips CJ, Voest EE

A phase II trial of imatinib therapy for metastatic medullary thyroid carcinoma.

J Clin Endocrinol Metab. 2007 Sep;92(9):3466-9. Epub 2007 Jun 19.

PubMed ID

17579194 [ View in PubMed

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Abstract

CONTEXT: Medullary thyroid carcinoma (MTC) metastasizes early in its clinical course. No effective systemic therapy is available. Generally (somatic or germline), mutations in the rearranged during transfection gene are considered essential in the pathogenesis of MTC. OBJECTIVE: We investigated imatinib, a tyrosine kinase inhibitor, as a potential treatment in patients with disseminated MTC. DESIGN: A phase II study was initiated using 600 mg imatinib daily with a possible dose increase to 800 mg in case of progression. Standard Response Evaluation Criteria in Solid Tumors were used using computed tomography or magnetic resonance imaging every 2 months. RESULTS: There were 15 patients with disseminated MTC treated for up to 12 months. No objective responses were observed. Four patients had stable disease over 24 months. Three patients stopped treatment due to toxic effects [fatigue (n = 2) and nausea (n = 1)]. In four cases the dose of imatinib was decreased because of toxicity [rash and malaise (n = 2) and laryngeal swelling (n = 2)]. Emergency tracheotomy was performed in two cases due to mucosal swelling of the larynx in patients with recurrent nerve palsy and a narrow vocal cleft. In nine patients with a history of a thyroidectomy, the dose of supplemental thyroid hormone was increased because of serious hypothyroidism. CONCLUSIONS: Imatinib therapy yielded no objective responses and induced considerable toxicity in patients with MTC. A minority of patients had stable disease. Patients with supplemented hypothyroidism or with recurrent nerve palsy are specifically at risk for serious adverse events and need special attention when treated with imatinib.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Imatinib	High affinity nerve growth factor receptor	Protein	Humans	Unknown	Antagonist	Details