Preliminary report of the use of Everolimus in a patient with progressive medullary thyroid carcinoma

T T Chung, M R Druce, K T Maher, S Grozinsky-Glasberg, D J Gross, J S Chambers, A B Grossman  

Introduction / Background

Medullary thyroid carcinoma (MTC) accounts for about 5-10% of all thyroid cancers, and while disease localised to the thyroid can be cured by surgery, there is no effective treatment for disseminated MTC.   Constitutive activation of the RET proto-oncogene is implicated in familial and a proportion of sporadic cases, and up-regulates the AKT/PI3-kinase/mTOR signal transduction pathway. Recent studies have shown that the inhibitor of mTOR, everolimus (RAD001, Novartis, Basel), can inhibit the proliferation of the TT cell line and human MTC tumour cells in vitro. Clinically, everolimus has been shown to attenuate the progression of some gastrointestinal neuroendocrine tumours, but its clinical use in MTC has not yet been evaluated.



An early progress report on the use of RAD001 in the clinical treatment of a patient with progressive MTC.


Materials and Methods

A patient with metastatic MTC received RAD001 (with institutional approval for compassionate use) and the effects evaluated.



The patient was a 57 year old lady with MEN2A and C634Y missense mutation in exon 11 of the RET proto-oncogene. She had presented with a right adrenal nodule (noted on imaging for recurrent urinary tract infection) and a calcitonin level of >10,000 ng/L (normal range <10 ng/L). She subsequently underwent laparoscopic adrenalectomy for pheochromocytoma and total thyroidectomy in 2003, when MTC was confirmed. Postoperative calcitonin was 16.2 ng/L but this rose progressively over time and pulmonary metastases were noted. A radiolabelled octreotide scan was negative, while a MIBG scan was positive in the neck but negative in the lung, suggesting poor therapeutic utility for radiolabelled MIBG. CT scans in March 2009 showed progressive disease and calcitonin had risen further, with a calculated doubling time of approximately 6 months. She commenced everolimus 10 mg daily for 12 months with good drug tolerance, apart from an increase in total and LDL cholesterol necessitating commencement of statin therapy, an asymptomatic decrease in haemoglobin from 13.8 to 10.6 g/dL and troublesome aphthous ulcerations. Currently, imaging is currently suggestive of stable disease. The mean of the 2 pre-therapy calcitonin levels was 5160 ng/L and is presently 5310 ng/L, suggesting that tumour progression has been halted. She remains asymptomatic.



Preliminary results of the use of everolimus  in a single patient with MTC have shown it to be well tolerated: after 12 months, disease which was previously progressive as assessed by cross-sectional imaging and calcitonin levels, appears to be stable. Further observation will be required to demonstrate whether a durable response of tumour burden and biochemical parameters can be achieved.