25 had thymoma, and 16 had thymic carcinoma; patients had a median of two previous systemic regimens . Treatment was well tolerated, with nausea, vomiting, and fatigue being the most frequent FTY720 adverse effects. Two patients achieved partial response , 25 had stable disease, and 13 had progressive disease; there were no responses among patients with thymic carcinoma. Median times to progression and survival were 5.8 and 19.1 months, respectively. Survival of patients with thymoma was significantly longer than that of patients with thymic carcinoma . Protein acetylation, regulatory T cell numbers, and circulating angiogenic factors did not predict outcome.Thymic epithelial malignancies are rare tumors, with an incidence of 0.15 per million person years,1 yet they represent 50% of anterior mediastinal tumors.
2 Little is known about the biology of these tumors, which are usually relatively indolent, with overall 5 year survival rates higher than 50% in surgical series.2 Surgery is the mainstay of treatment for these tumors, and stage and completeness of resection are major prognostic factors.3WHOhistologic classification has also been shown Irinotecan molecular weight to be important in determining prognosis, with thymic carcinoma having a significantly worse prognosis than thymoma.3 Patients who present with advanced disease or large inoperable mediastinal masses, in addition to the 10%to30%who experience recurrence despite radical surgery, usually undergo chemotherapy. There are several active regimens, most of which contain cisplatin, with response rates varying from 30% to 70%.
3 Unfortunately, patients with advanced disease are not cured by chemotherapy, even if response rates are high, and duration of responses Pemetrexed price is long. There is no standard treatment for thymic malignancies after failure of platinum based chemotherapy. Few phase II studies have been performed in patients with this disease Irinotecan ic50 because of its rarity. A response rate of approximately 20% has been demonstrated with pemetrexed in patients with recurrent thymic malignancies,4 whereas epidermal growth factor receptor and c kit tyrosine kinase inhibitors have failed to show activity in phase II studies,3 which can be explained by the rarity of mutations in these genes.5,6 There is a need to test novel agents in thymic malignancies, possibly on the basis of a better understanding of the biology of the disease.
Histone deacetylases can regulate expression of tumor suppressor genes and activities of transcriptional factors involved in cancer initiation and progression through alteration of either DNA or the structural components of chromatin.7 Gene repression through acetylation has been clinically validated protein kinases with several inhibitors of HDACs. Vorinostat and depsipeptide have recently been approved by the US Food and Drug Administration for the treatment of cutaneous T cell lymphoma. Several other inhibitors are currently being developed. Belinostat is a hydroxamic acid pan HDAC inhibitor presently undergoing phase II studies in several malignancies. In a phase I study of this agent, one patient with thymoma had a minor response that lasted for 17 months while receiving treatment. 8 In general, the drug is well tolerated. We report results from a phase II study of belinostat in patients with recurrent or refractory .