期刊
CLINICAL & TRANSLATIONAL ONCOLOGY
卷 25, 期 7, 页码 2090-2098出版社
SPRINGER INT PUBL AG
DOI: 10.1007/s12094-023-03085-w
关键词
Granulosa cell ovarian cancer; Ketoconazole; Hormonetherapy
类别
Digoxin can inhibit the growth of gastrointestinal tumor cells and induce apoptosis, indicating its potential anti-tumor effect.
BackgroundGranulosa 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.MethodsWe 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.ResultsFrom 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 center dot 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.ConclusionKetoconazole 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). ClinicalTrials.gov IdentifierNCT01584297.
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