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Efficacy of imatinib mesylate in advanced medullary thyroid carcinoma

Endocrine Practice, Brückenstr. 21, 69120 Heidelberg, Germany, ¹ Department of Radiology, German Cancer Centre, 69120 Heidelberg, Germany and ² Department of Nuclear Medicine, University of Heidelberg, 69120 Heidelberg, Germany

(Correspondence should be addressed to K Frank-Raue; Email: karin.frankraue{at}raue-endokrinologie.de)

Objective: Medullary thyroid carcinoma (MTC) is often associated with gain-of-function mutations in the RET proto-oncogene, which is found in all hereditary cases and most sporadic cases. The activated RET receptor tyrosine kinase can be inhibited by tyrosine kinase inhibitors in vitro. We evaluated the efficacy of treatment with imatinib mesylate, a tyrosine kinase inhibitor, in patients with advanced MTC.

Design and patients: In this open-label clinical trial, nine patients, eight with sporadic and one with hereditary MTC, with unresectable, measurable, progressive metastases were treated with imatinib mesylate 600 mg daily. The tumour response to imatinib was evaluated after 3, 6 and 12 months by computed tomography and after 1 month by ¹⁸F-fluoro-2-deoxy D-glucose position-emission tomographic scanning. The median duration of therapy was 8 months.

Results: Overall, stable disease occurred in five patients for up to 6 months and in one patient for up to 12 months, with a median duration of progression-free survival of 6 months. Four patients had progressive disease after 12 months. One patient stopped therapy after 2 weeks because of worsening of diarrhoea. Therapy was well tolerated, although transient mild-to-moderate nausea (n = 3), oedema (n = 3), diarrhoea (n = 2) and skin rash (n = 2) were observed.

Conclusion: Imatinib mesylate is well tolerated, no tumour remission was observed, only transient stable disease was achieved in some patients with advanced MTC.