Beneficial effects of sorafenib on tumor progression, but not on radioiodine uptake, in patients with differentiated thyroid carcinoma.
OBJECTIVE
Treatment options for patients with radioactive iodine (RaI) refractory metastases of differentiated thyroid carcinoma (DTC) are limited. We studied the effects of the multitarget tyrosine kinase inhibitor sorafenib on the reinduction of RaI uptake and tumor progression.


METHODS
Open, single center, single arm 26-week prospective phase II study with open-ended extension.


METHODS
We treated 31 patients with progressive metastatic or locally advanced RaI refractory DTC with sorafenib 400 mg b.i.d. The primary endpoint was reinduction of RaI uptake at 26 weeks. Additional endpoints were the radiological response and the influence of bone metastases.


RESULTS
At 26 weeks of sorafenib therapy, no reinduction of RaI uptake at metastatic sites was observed, but 19 patients (59%) had a clinical beneficial response, eight of whom had a partial response (25%) and 11 had stable disease (34%). Seven patients had progressive disease (22%). Sorafenib was significantly less effective in patients with bone metastases. The estimated median progression free survival was 58 weeks (95% confidence interval, CI, 47-68). In general, thyroglobulin (Tg) response (both unstimulated and TSH stimulated) reflected radiological responses. The median time of the nadir of Tg levels was 3 months. Responses were not influenced by histological subtype, mutational status or other variables. No unusual side effects were observed.


CONCLUSIONS
Sorafenib has a beneficial effect on tumor progression in patients with metastatic DTC, but was less effective in patients with bone metastases. Diagnostic whole body scintigraphy did not reveal an effect of sorafenib on the reinduction of RaI uptake.
Department of Endocrinology and Metabolism, Leiden University Medical Center, PO Box 9600, 2300 RC Leiden, The Netherlands.
Hendrieke
H
Hoftijzer
Karen A
KA
Heemstra
Hans
H
Morreau
Marcel P
MP
Stokkel
Eleonora P
EP
Corssmit
Hans
H
Gelderblom
Karin
K
Weijers
Alberto M
AM
Pereira
Maya
M
Huijberts
Ellen
E
Kapiteijn
Johannes A
JA
Romijn
Johannes W
JW
Smit
D018263:Adenocarcinoma, Follicular / Q000188:drug therapy / Q000532:radiotherapy; D000368:Aged; D000369:Aged, 80 and over; D001557:Benzenesulfonates / Q000009:adverse effects / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000188:drug therapy / Q000532:radiotherapy / Q000556:secondary; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007457:Iodine Radioisotopes / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009536:Niacinamide / Q000031:analogs & derivatives; D010671:Phenylurea Compounds; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011725:Pyridines / Q000009:adverse effects / Q000627:therapeutic use*; D000077157:Sorafenib; D013954:Thyroglobulin / Q000378:metabolism; D013964:Thyroid Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy
D001557:Benzenesulfonates; D007457:Iodine Radioisotopes; D010671:Phenylurea Compounds; D011725:Pyridines; D009536:Niacinamide; D013954:Thyroglobulin; D000077157:Sorafenib; D011505:Protein-Tyrosine Kinases