Luciana Audi de Castroneves1, Marcelo Vailati Negrão2, Ricardo Miguel Costa de Freitas3, Carla Papadia1, José Viana Lima4, Julia T Fukushima5, Eduardo Furquim Simão6, Marco Aurélio Vamondes Kulcsar7, Marcos Roberto Tavares8, Alexander Augusto de Lima Jorge9, Gilberto de Castro2, Paulo Marcelo Hoff2, Ana Oliveira Hoff1. 1. 1 Endocrinology Department; Instituto do Câncer do Estado de São Paulo , Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil . 2. 2 Medical Oncology Department; Instituto do Câncer do Estado de São Paulo , Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil . 3. 3 Radiology Department; Instituto do Câncer do Estado de São Paulo , Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil . 4. 4 Endocrinology Department, Irmandade da Santa Casa da Misericórdia de São Paulo , São Paulo, Brazil . 5. 5 Intensive Care Unit; Instituto do Câncer do Estado de São Paulo , Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil . 6. 6 Faculdade de Medicina da Universidade de São Paulo , São Paulo, Brazil . 7. 7 Head and Neck Surgery Department; Instituto do Câncer do Estado de São Paulo , Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil . 8. 8 Head and Neck Surgery Department; Hospital das Clínicas , Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil . 9. 9 Genetics Endocrinology LIM 25; Hospital das Clínicas , Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil .
Abstract
BACKGROUND: Treatment of advanced medullary thyroid carcinoma (MTC) was recently improved with the approval of vandetanib and cabozantinib. However, there is still a need to explore sequential therapy with more than one tyrosine kinase inhibitor (TKI) and to explore alternative therapies when vandetanib and cabozantinib are not available. This study reports the authors' experience with sorafenib as a treatment for advanced MTC. METHODS: This is a retrospective longitudinal study of 13 patients with progressive metastatic MTC treated with sorafenib 400 mg twice daily between December 2011 and January 2015. The primary endpoints were to evaluate response and progression-free survival (PFS) in patients treated with sorafenib outside a clinical trial. The secondary endpoint was an assessment of the toxicity profile. One patient was excluded because of a serious allergic skin rash one week after starting sorafenib. RESULTS: The analysis included 12 patients with metastatic MTC (median age 48 years), 10 with sporadic and 2 with hereditary disease. The median duration of treatment was 11 months, and the median follow-up was 15.5 months. At data cutoff, 2/12 (16%) patients were still on treatment for 16 and 34 months. According to Response Evaluation Criteria in Solid Tumors analysis, 10 (83.3%) patients showed stable disease, and two (16.6%) had progression of disease; no partial response was observed. The median PFS was nine months. However, three patients with extensive and rapidly progressive disease died within three months of sorafenib treatment. The median PFS excluding these three patients was 12 months. Adverse events (AE) occurred in nine (75%) patients. The main AEs were skin toxicity, weight loss, and fatigue. Five (41.6%) patients needed dose reduction, and one patient discontinued treatment because of toxicity. CONCLUSIONS: Treatment with sorafenib in progressive metastatic MTC is well tolerated and resulted in disease control and durable clinical benefit in 75% of patients. Sorafenib treatment could be considered when vandetanib and cabozantinib are not available or after failing these drugs.
BACKGROUND: Treatment of advanced medullary thyroid carcinoma (MTC) was recently improved with the approval of vandetanib and cabozantinib. However, there is still a need to explore sequential therapy with more than one tyrosine kinase inhibitor (TKI) and to explore alternative therapies when vandetanib and cabozantinib are not available. This study reports the authors' experience with sorafenib as a treatment for advanced MTC. METHODS: This is a retrospective longitudinal study of 13 patients with progressive metastatic MTC treated with sorafenib 400 mg twice daily between December 2011 and January 2015. The primary endpoints were to evaluate response and progression-free survival (PFS) in patients treated with sorafenib outside a clinical trial. The secondary endpoint was an assessment of the toxicity profile. One patient was excluded because of a serious allergic skin rash one week after starting sorafenib. RESULTS: The analysis included 12 patients with metastatic MTC (median age 48 years), 10 with sporadic and 2 with hereditary disease. The median duration of treatment was 11 months, and the median follow-up was 15.5 months. At data cutoff, 2/12 (16%) patients were still on treatment for 16 and 34 months. According to Response Evaluation Criteria in Solid Tumors analysis, 10 (83.3%) patients showed stable disease, and two (16.6%) had progression of disease; no partial response was observed. The median PFS was nine months. However, three patients with extensive and rapidly progressive disease died within three months of sorafenib treatment. The median PFS excluding these three patients was 12 months. Adverse events (AE) occurred in nine (75%) patients. The main AEs were skin toxicity, weight loss, and fatigue. Five (41.6%) patients needed dose reduction, and one patient discontinued treatment because of toxicity. CONCLUSIONS: Treatment with sorafenib in progressive metastatic MTC is well tolerated and resulted in disease control and durable clinical benefit in 75% of patients. Sorafenib treatment could be considered when vandetanib and cabozantinib are not available or after failing these drugs.
Authors: Lisly Chéry; Leonardo D Borregales; Bryan Fellman; Diana L Urbauer; Naveen Garg; Nathan Parker; Matthew H G Katz; Christopher G Wood; Jose A Karam Journal: Urology Date: 2017-07-10 Impact factor: 2.649
Authors: Michael K Kießling; Jan P Nicolay; Tabea Schlör; Claus-Detlev Klemke; Dorothee Süss; Peter H Krammer; Karsten Gülow Journal: Oncotarget Date: 2017-07-11
Authors: Masahiro Sonoshita; Alex P Scopton; Peter M U Ung; Matthew A Murray; Lisa Silber; Andres Y Maldonado; Alexander Real; Avner Schlessinger; Ross L Cagan; Arvin C Dar Journal: Nat Chem Biol Date: 2018-01-22 Impact factor: 15.040