***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: 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 . DESIGN Open , single center , single arm 26-week prospect i ve 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 PURPOSE Patients with advanced , incurable thyroid cancer not amenable to surgery or radioactive iodine ( (131)I ) therapy have few satisfactory therapeutic options . This multi-institutional study assessed the activity and safety of axitinib , an oral , potent , and selective inhibitor of vascular endothelial growth factor receptors ( VEGFR ) 1 , 2 , and 3 in patients with advanced thyroid cancer . PATIENTS AND METHODS Patients with thyroid cancer of any histology that was resistant or not appropriate for (131)I were enrolled onto a single-arm phase II trial to receive axitinib orally ( starting dose , 5 mg twice daily ) . Objective response rate ( ORR ) by Response Evaluation Criteria in Solid Tumors was the primary end point . Secondary end points included duration of response , progression-free survival ( PFS ) , overall survival , safety , and modulation of soluble ( s ) VEGFR . RESULTS Sixty patients were enrolled . Partial responses were observed in 18 patients , yielding an ORR of 30 % ( 95 % CI , 18.9 to 43.2 ) . Stable disease lasting > or = 16 weeks was reported in another 23 patients ( 38 % ) . OBJECTIVE responses were noted in all histologic subtypes . Median PFS was 18.1 months ( 95 % CI , 12.1 to not estimable ) . Axitinib was generally well tolerated , with the most common grade > or = 3 treatment-related adverse event being hypertension ( n = 7 ; 12 % ) . Eight patients ( 13 % ) discontinued treatment because of adverse events . Axitinib selectively decreased sVEGFR-2 and sVEGFR-3 plasma concentrations versus sKIT , demonstrating its targeting of VEGFR . CONCLUSION Axitinib is a selective inhibitor of VEGFR with compelling antitumor activity in all histologic subtypes of advanced thyroid cancer PURPOSE Given the molecular pathophysiology of thyroid cancer and the spectrum of kinases inhibited by sorafenib , including Raf kinase , vascular endothelial growth factor receptors , platelet-derived growth factor receptor , and RET tyrosine kinases , we conducted an open-label phase II trial to determine the efficacy of sorafenib in patients with advanced thyroid carcinoma . PATIENTS AND METHODS Eligible patients with metastatic , iodine-refractory thyroid carcinoma received sorafenib 400 mg orally twice daily . Responses were measured radiographically every 2 to 3 months . The study end points included response rate , progression-free survival ( PFS ) , and best response by Response Evaluation Criteria in Solid Tumors . RESULTS Thirty patients were entered onto the study and treated for a minimum of 16 weeks . Seven patients ( 23 % ; 95 % CI , 0.10 to 0.42 ) had a partial response lasting 18 + to 84 weeks . Sixteen patients ( 53 % ; 95 % CI , 0.34 to 0.72 ) had stable disease lasting 14 to 89 + weeks . Seventeen ( 95 % ) of 19 patients for whom serial thyroglobulin levels were available showed a marked and rapid response in thyroglobulin levels with a mean decrease of 70 % . The median PFS was 79 weeks . Toxicity was consistent with other sorafenib trials , although a single patient died of liver failure that was likely treatment related . CONCLUSION Sorafenib has clinical ly relevant antitumor activity in patients with metastatic , iodine-refractory thyroid carcinoma , with an overall clinical benefit rate ( partial response + stable disease ) of 77 % , median PFS of 79 weeks , and an overall acceptable safety profile . These results represent a significant advance over chemotherapy in both response rate and PFS and support further investigation of this agent in these patients OBJECTIVE To determine the efficacy of gefitinib in patients with advanced thyroid cancer . DESIGN In this open-label phase II trial , 27 patients with radioiodine-refractory , locally advanced , or metastatic thyroid cancer were treated with 250 mg of daily gefitinib . Histologic subtypes included papillary ( 41 % ) , follicular ( 22 % ) , anaplastic ( 19 % ) , medullary ( 15 % ) , and Hürthle cell carcinomas ( 4 % ) . The primary endpoint was overall response rate . Secondary endpoints were toxicity , progression-free survival ( PFS ) , and overall survival ( OS ) . MAIN OUTCOMES There were no objective responses among the 25 patients evaluated . After 3 , 6 , and 12 months of treatment , 48 % , 24 % , and 12 % of patients had stable disease ( SD ) , respectively . Median PFS and OS were 3.7 and 17.5 months , respectively . Five patients with SD had a decrease in thyroglobulin ( Tg ) to < 90 % of baseline that was maintained for at least 3 months . CONCLUSIONS Although gefitinib therapy did not result in any tumor responses , 32 % of patients had reductions in tumor volume that did not meet criteria for partial response rate . Along with falling Tg levels and prolonged SD in a subset of patients , this may indicate biologic activity 
    Output:
    
V and etanib can significantly improve PFS .
Though it has some side effects , it is still a promising agent in the treatment of advanced or metastasized thyroid cancer , especially in those with metastasized or advanced medullary thyroid carcinoma