pyrimidinones and lenvatinib

Anaplastic thyroid cancer (ATC) has dismal prognosis and there is no effective treatment. We aimed to evaluate the efficacy of tyrosine kinase inhibitor (TKI) therapy in real-world clinic and to suggest the most effective treatment modality according to the combination of treatments.. This retrospective study evaluated clinical outcomes and cause of death with multimodal treatments in patients with ATC at Samsung Medical Center.. A total of 120 patients received anti-cancer treatment for ATC. Seventy-seven (64.2%) patients underwent surgery, 64 (53.3%) received radiotherapy, 29 (24.2%) received cytotoxic chemotherapy, and 19 (15.8%) received TKI therapy. In the TKI therapy group, eight achieved partial response (three with lenvatinib and five with dabrafenib plus trametinib), and two patients with lenvatinib showed stable disease. Median progression-free survival (PFS) of the TKI therapy group was 2.7 months (range: 0.1-12.7) and their median overall survival (OS) was 12.4 months (range: 1.7-47.7). Patients who received surgery or radiotherapy for local control showed superior OS than those who did not. In a multivariate analysis, surgery, TKI therapy, younger age, and no distant metastasis were associated with favorable OS. The combination of surgery, radiotherapy, and TKI therapy (median OS: 34.3 months, 6-month survival rates: 77.8%) was the most effective. Compared to the era without TKI therapy, distant metastasis has recently become the major cause of death in ATC over airway problems.. Multimodality treatment including TKI therapy demonstrated prolonged survival with dabrafenib plus trametinib as the most effective therapeutic option demonstrated for BRAF mutant ATC patients.

Topics: Age Factors; Aged; Antineoplastic Agents; Combined Modality Therapy; Female; Humans; Imidazoles; Male; Middle Aged; Oximes; Phenylurea Compounds; Prognosis; Protein Kinase Inhibitors; Pyridones; Pyrimidinones; Quinolines; Retrospective Studies; Thyroid Carcinoma, Anaplastic; Thyroid Neoplasms; Treatment Outcome

Patients with anaplastic thyroid cancer (ATC) have a dismal prognosis, despite systemic cytotoxic chemotherapy. The objective of this study was to investigate the efficacy and safety of targeted therapy in ATC patients when used outside of a clinical trial.. This is a retrospective review from April 2015 to May 2016 at a single academic institution where 16 ATC patients receiving targeted therapy outside of a clinical trial were studied. Ten patients (eight BRAF wild type and two BRAF. The majority of patients (63%) were men, and all had distant metastases or radiation-resistant primary disease at the time of treatment. In the entire cohort, 6/16 (38%) had a partial response, 6/16 (38%) had stable disease, and 2/16 (12%) had progressive disease. Two (12%) patients died before restaging. Median follow-up time was 11.8 months. Median progression-free survival was 3.7 months [confidence interval 1.8-7.6] in the entire cohort, 2.7 months for lenvatinib, and 5.2 months for dabrafenib plus trametinib. Median OS was 6.3 months [confidence interval 1.8-7.6] for the entire cohort, 3.9 months for lenvatinib, and 9.3 months for dabrafenib plus trametinib. Adverse events were as expected and manageable.. Targeted therapies, lenvatinib, and dabrafenib plus trametinib (for BRAF

Topics: Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Female; Humans; Imidazoles; Male; Middle Aged; Mutation; Oximes; Phenylurea Compounds; Prognosis; Progression-Free Survival; Proto-Oncogene Proteins B-raf; Pyridones; Pyrimidinones; Quinolines; Retrospective Studies; Thyroid Carcinoma, Anaplastic; Thyroid Neoplasms; Treatment Outcome