Efficacy of imatinib mesylate in advanced medullary thyroid carcinoma.
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.


METHODS
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 (18)F-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.


CONCLUSIONS
Imatinib mesylate is well tolerated, no tumour remission was observed, only transient stable disease was achieved in some patients with advanced MTC.
Frank-Raue
Karin
K
Endocrine Practice, Brückenstr. 21, 69120 Heidelberg, Germany. karin.frankraue@raue-endokrinologie.de
Fabel
Michael
M
Delorme
Stefan
S
Haberkorn
Uwe
U
Raue
Friedhelm
F
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001549:Benzamides; D002116:Calcitonin / Q000097:blood; D018276:Carcinoma, Medullary / Q000000981:diagnostic imaging / Q000188:drug therapy*; D005260:Female; D019788:Fluorodeoxyglucose F18; D018095:Germ-Line Mutation / Q000235:genetics; D006801:Humans; D000068877:Imatinib Mesylate; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000009:adverse effects / Q000627:therapeutic use*; D049268:Positron-Emission Tomography; D000090063:Proto-Oncogene Mas; D011743:Pyrimidines / Q000009:adverse effects / Q000627:therapeutic use*; D016019:Survival Analysis; D013964:Thyroid Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy*
D000970:Antineoplastic Agents; D001549:Benzamides; C000715470:MAS1 protein, human; D010879:Piperazines; D000090063:Proto-Oncogene Mas; D011743:Pyrimidines; D019788:Fluorodeoxyglucose F18; D000068877:Imatinib Mesylate; D002116:Calcitonin