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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
Garcia-Donas, Jesus; Prieto, Mario; Rodriguez-Moreno, Juan Francisco; Navarro, Paloma; Hurtado, Alicia; Garrigos, Laia; Taus, Alvaro; Santaballa, Ana; Redondo, Andres; Vidal, Laura.
Affiliation
  • Garcia-Donas, Jesus; HM Hospitales-Centro Integral Oncológico HM Clara Campal. Madrid. Spain
  • Prieto, Mario; HM Hospitales-Centro Integral Oncológico HM Clara Campal. Madrid. Spain
  • Rodriguez-Moreno, Juan Francisco; HM Hospitales-Centro Integral Oncológico HM Clara Campal. Madrid. Spain
  • Navarro, Paloma; HM Hospitales-Centro Integral Oncológico HM Clara Campal. Madrid. Spain
  • Hurtado, Alicia; Hospital Universitario Fundación Alcorcón. Alcorcón. Spain
  • Garrigos, Laia; Hospital Universitario del Mar. Barcelona. Spain
  • Taus, Alvaro; Hospital Universitario La Fe. Valencia. Spain
  • Santaballa, Ana; Hospital Universitario La Paz. Madrid. Spain
  • Redondo, Andres; Hospital Universitario Clinico de Barcelona. Barcelona. Spain
  • Vidal, Laura; Hospital de Navarra. Pamplona. Spain
Clin. transl. oncol. (Print) ; 25(7): 2090-2098, jul. 2023. graf
Article in English | IBECS | ID: ibc-222380
Responsible library: ES1.1
Localization: ES15.1 - BNCS
ABSTRACT
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) (AU)
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Collection: National databases / Spain Database: IBECS Main subject: Ovarian Neoplasms / Steroid 17-alpha-Hydroxylase / Ketoconazole Limits: Female / Humans Language: English Journal: Clin. transl. oncol. (Print) Year: 2023 Document type: Article Institution/Affiliation country: HM Hospitales-Centro Integral Oncológico HM Clara Campal/Spain / Hospital Universitario Clinico de Barcelona/Spain / Hospital Universitario Fundación Alcorcón/Spain / Hospital Universitario La Fe/ Spain / Hospital Universitario La Paz/Spain / Hospital Universitario del Mar/Spain / Hospital de Navarra/Spain
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Collection: National databases / Spain Database: IBECS Main subject: Ovarian Neoplasms / Steroid 17-alpha-Hydroxylase / Ketoconazole Limits: Female / Humans Language: English Journal: Clin. transl. oncol. (Print) Year: 2023 Document type: Article Institution/Affiliation country: HM Hospitales-Centro Integral Oncológico HM Clara Campal/Spain / Hospital Universitario Clinico de Barcelona/Spain / Hospital Universitario Fundación Alcorcón/Spain / Hospital Universitario La Fe/ Spain / Hospital Universitario La Paz/Spain / Hospital Universitario del Mar/Spain / Hospital de Navarra/Spain
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