2026-05-17T01:15:59Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/260442025-12-18T12:56:20Zcom_20.500.12105_2052com_20.500.12105_2051col_20.500.12105_19616

00925njm 22002777a 4500 dc Garcia-Donas, Jesus author Hurtado, Alicia author Garrigos, Laia author Santaballa, Ana author Redondo, Andres author Vidal, Laura author Lainez, Nuria author Guerra, Eva author Rodriguez, Victor author Cueva, Juan author Bover, Isabel author Palacio, Isabel author Rubio, Maria Jesus author Prieto, Mario author Lopez-Guerrero, Jose Antonio author Rodriguez-Moreno, Juan Francisco author Garcia-Casado, Zaida author Garcia-Martinez, Elena author Taus, Alvaro author Perez de Castro, Ignacio author Navarro, Paloma author Grande, Enrique author Spanish Group for Research in Orphan, Infrequent Tumors (GETHI) author 2023-07 Background: Granulosa cell ovarian tumor (GCT) is characterized by a pathognomonic mutation in the FOXL2 gene (402 C > G) that leads to an overactivation of steroidogenesis. CYP17 is a key enzyme in such process and can be inhibited by ketoconazole. Methods: We designed a phase II clinical trial to assess the efficacy of ketoconazole in advanced GCT and conducted several in vitro studies to support the clinical findings. Results: From October 1st 2012 to January 31st 2014, six evaluable patients were recruited in ten hospitals of the Spanish Group for Transversal Oncology and Research in Orphan and Infrequent Tumors" (GETTHI). FOXL2 (402C > G) mutation was confirmed in three; two cases were wild type and it could not be assessed in one. No objective response by RECIST was observed, but five cases achieved stable disease longer than 12 months. Median progression-free survival was 14.06 months (CI 95% 5.43-22.69) for the whole study population (3.38 and 13.47 months for wild-type cases and 14.06, 20.67 and 26.51 for those with confirmed FOXL2 mutation). Median overall survival was 22·99 months (CI 95% 8.99-36.99). In vitro assays confirmed the activity of ketoconazole in this tumor and suggested potential synergisms with other hormone therapies. Conclusion: Ketoconazole has shown activity in advanced GCT in clinical and in vitro studies. Based on these data, an orphan designation was granted by the European Medicines Agency for ketoconazole in GCT (EU/3/17/1857). Gov identifier: NCT01584297. Garcia-Donas J, Hurtado A, Garrigos L, Santaballa A, Redondo A, Vidal L, Lainez N, Guerra E, Rodriguez V, Cueva J, Bover I, Palacio I, Rubio MJ, Prieto M, Lopez-Guerrero JA, Rodriguez-Moreno JF, Garcia-Casado Z, Garcia-Martinez E, Taus A, de Castro IP, Navarro P, Grande E; Spanish Group for Research in Orphan, Infrequent Tumors (GETHI). Open-label phase II clinical trial of ketoconazole as CYP17 inhibitor in metastatic or advanced non-resectable granulosa cell ovarian tumors: the GREKO (GRanulosa Et KetOconazole) trial, GETHI 2011-03. Clin Transl Oncol. 2023 Jul;25(7):2090-2098. 10.1007/s12094-023-03085-w 1699-3055 1699-048X Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico 36708371 https://hdl.handle.net/20.500.12105/26044 Granulosa cell ovarian cancer Hormonetherapy Ketoconazole Open-label phase II clinical trial of ketoconazole as CYP17 inhibitor in metastatic or advanced non-resectable granulosa cell ovarian tumors: the GREKO (GRanulosa Et KetOconazole) trial, GETHI 2011-03