Efficacy of imatinib (Glivec®) in metastasising medullary thyroid carcinoma

Objectives: Medullary thyroid carcinoma (MTC) results from gain-of-function mutations in the RET proto-oncogene, which encodes a transmembrane tyrosine kinase receptor. In vitro the tyrosine kinase inhibitor imatinib (Glivec®) is able to retard cell growth in MTC cell lines and may activate apoptosis. We evaluated the efficacy of treatment with imatinib in patients with progressive metastasising MTC.

Methods: Eight patients (2 female, 6 male, mean age 48 years) with MTC (7 sporadic, 1 hereditary=MEN2b) and locoregional (n=8) and distant metastases (lung n=3; liver n=4; bone n=3) as well as elevated calcitonin (6200–104692, mean 38300 pg/ml) and CEA levels (20–590, mean 251 ng/ml) participated in this study. We assessed antitumor response of 600mg imatinib (Glivec®) taken orally by ultrasound scanning, cervical, mediastinal, and abdominal CT before as well as 3, 6,and 12 months after initiation of treatment. Whole-body F-18-FDG-PET was performed before, after 4 weeks and at the end of the study (12 months).

Results: Therapy with imatinib was well tolerated, although mild-to-moderate edema (n=2) and diarrhea (n=2) were observed. In one case, therapy was stopped after 2 weeks because of diarrhea. One patient died of progressive disease after 3 months; one patient stopped therapy after 3 month because of progression. Four of the remaining 5 patients have completed one year of treatment. One of these had progressive disease with doubling of metastases and increasing tumor markers within one year. The four remaining patients radiologically had stable disease with inceasing calcitonin and constant CEA. Overall, half of the patients achieved stable disease, but no reduction in tumor burden.

Conclusion: Imatinib induced a reduction of tumor growth after pretherapeutic progression in half of the patients with advanced progressive metastasising medullary thyroid carcinoma. Imatinib was well tolerated with minor adverse effects.