***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: 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 BACKGROUND Rosiglitazone is a peroxisome proliferator-activated receptor gamma ( PPARgamma ) agonist that has been shown to induce differentiation , cell cycle arrest , and apoptosis in a variety of human cancers including thyroid cancer . METHODS Ten patients with differentiated thyroid cancer were enrolled in an open-label , phase II trial of oral rosiglitazone treatment ( 4 mg daily for 1 week , then 8 mg daily for 7 weeks ) . The levels of PPARgamma receptor mRNA and protein expression were determined in the patient 's neoplasm . RESULTS Of 10 patients , 4 had positive radioiodine scans after rosiglitazone therapy with uptake in the neck in 3 patients and in the pelvis in 1 patient . After treatment , the serum thyroglobulin level decreased in 2 patients , increased in 5 patients , and was stable in 3 patients . No patient developed clinical ly important toxicity associated with rosiglitazone treatment . We found no relationship in the level of PPARgamma mRNA and protein expression in patients who had radioiodine uptake compared with those who did not . CONCLUSIONS Our findings suggest that rosiglitazone treatment may induce radioiodine uptake in some patients with thyroglobulin-positive and radioiodine-negative differentiated thyroid cancer . We found no relationship between the expression level of the PPARgamma mRNA and protein in the neoplasm and radioiodine uptake status after rosiglitazone therapy , question ing the potential pathway of effect BACKGROUND There are no known effective therapies for distantly metastatic , rapidly progressive thyroid carcinomas unresponsive to radioiodine . OBJECTIVE Since thyroid carcinomas are hypervascular and thalidomide is antiangiogenic , we assessed thalidomide 's tumoristatic effects and toxicity in a phase II trial . DESIGN Thirty-six patients with follicular , papillary , insular , or medullary thyroid carcinomas and distant , radioiodine-unresponsive metastases ( volumes increasing > or= 30 % per year before entry ) were accrued between July 2001 and December 2002 .  Daily thalidomide started at 200 mg , increasing over 6 weeks to 800 mg or maximum tolerated dose . Toxicities and responses were assessed at 8-week intervals with tumor volume assessment s. MAIN OUTCOMES Twenty-eight of 36 patients were evaluable , 5 with partial responses ( PR : 18 % ; 95 % confidence interval [ 95 % CI ] : 6 - 37 % ) and 9 patients with stable disease ( SD : 32 % ; 95 % CI : 12 - 42 % ) for overall 50 % response ( 95 % CI : 31 - 69 % ) . Median PR duration was 4 months ( range : 2 - 6 months ) , and SD duration was 6 months ( range : 2 - 14 months ) . Median survival was 23.5 months for responders ( PR + SD ) and 11 months for nonresponders . Most frequent toxicity was fatigue ( 69 % grade 1 - 2 , 8 % grade 3 - 4 ) . Four patients had grade 3 - 4 infections ( without neutropenia ) , one had pericardial effusion , and one had pulmonary embolus . CONCLUSIONS Thalidomide confers therapeutic benefit in subsets of thyroid cancer patients with rapidly progressive , distantly metastatic disease A r and omized evaluation of the effectiveness and toxicity of the combination of doxorubicin and cisplatin and of doxorubicin alone in patients with advanced thyroid carcinoma was carried out . Ninety‐two patients were entered and 84 were evaluable . They were stratified according to histological classification , Eastern Cooperative Oncology Group ( ECOG ) performance status , and metastatic sites . Forty‐one patients received doxorubicin as a single agent and seven had partial response ( 17 % ) . Forty‐three patients received the combination , and there were five complete and six partial responses ( combined response rate of 26 % ) . This difference for overall response rate is not significant ( P > 0.1 ) . However , five complete responses were seen in the combination‐treatment group , whereas none were observed in the single‐agent treatment group ; a significant difference was obtained ( P = 0.03 ) . Four of these five complete responders survived for more than 2 years , and two patients remained in a complete response after the discontinuation of therapy and are still alive . None of the partial responses exceeded 2 years in duration . The life‐threatening toxicities from chemotherapy occurred in five patients treated with the combination of drugs and two treated with doxorubicin alone . However , none of the toxicities were fatal . The study has shown clearly that the quality of response achieved by the combination of drugs is far superior to that achieved by single‐agent chemotherapy 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 BACKGROUND The expression of vascular endothelial growth factor ( VEGF ) is characteristic of differentiated thyroid cancer and is associated with aggressive tumor behavior and a poor clinical outcome . Motesanib diphosphate ( AMG 706 ) is a novel oral inhibitor of VEGF receptors , platelet-derived growth-factor receptor , and KIT . METHODS In an open-label , single-group , phase 2 study , we treated 93 patients who had progressive , locally advanced or metastatic , radioiodine-resistant differentiated thyroid cancer with 125 mg of motesanib diphosphate , administered orally once daily . The primary end point was an objective response as assessed by an independent radiographic review . Additional end points included the duration of the response , progression-free survival , safety , and changes in serum thyroglobulin concentration . RESULTS Of the 93 patients , 57 ( 61 % ) had papillary thyroid carcinoma . The objective response rate was 14 % . Stable disease was achieved in 67 % of the patients , and stable disease was maintained for 24 weeks or longer in 35 % ; 8 % had progressive disease as the best response . The Kaplan-Meier estimate of the median duration of the response was 32 weeks ( the lower limit of the 95 % confidence interval [ CI ] was 24 ; the upper limit could not be estimated because of an insufficient number of events ) ; the estimate of median progression-free survival was 40 weeks ( 95 % CI , 32 to 50 ) . Among the 75 patients in whom thyroglobulin analysis was performed , 81 % had decreased serum thyroglobulin concentrations during treatment , as compared with baseline levels . The most common treatment-related adverse events were diarrhea ( in 59 % of the patients ) , hypertension ( 56 % ) , fatigue ( 46 % ) , and weight loss ( 40 % ) . CONCLUSIONS Motesanib diphosphate can induce partial responses in patients with advanced or metastatic differentiated thyroid cancer that is progressive . ( Clinical Trials.gov number , NCT00121628 . 
    Output:
    
There is currently no reliable evidence available from r and omized controlled trials regarding the bene fi ts and harms of the use of  angiogenesis-inhibitors  for treating advanced thyroid cancer .