title: Sunitinib in the therapy of malignant paragangliomas: report on the efficacy in a SDHB mutation carrier and review of the literature.
abstract: Metastatic pheochromocytomas (PHEOs) and paragangliomas (sPGLs) are rare neural crest-derived tumors with a poor prognosis. About 50% of them are due to germ-line mutations of the SDHB gene. At present, there is no cure for these tumors. Their therapy is palliative and represented by different options among which antiangiogenic drugs, like sunitinib, have been hypothesized to be effective especially in malignant SDHB mutated tumors. We report the effects of sunitinib therapy in a SDHB mutation carrier affected by a malignant sPGL. During 101 weeks of therapy at different doses, sunitinib was able to cause a partial response and then a stable disease for a total of 78 weeks. This favorable response is the longest, out of the 35 so far reported in the literature, registered in a patient treated exclusively with sunitinib but, similarly to the other responses, the effect was limited in time. From our analysis of the scanty data present in the literature, the effect of sunitinib does not seem to be different among wild-type patients and those carrying a cluster 1 germ-line mutation. Sunitinib seems able to slow the disease progression in some patients with malignant PHEO/PGL and therefore may represent a therapeutic option, although randomized controlled studies are needed to assess its efficacy definitively in the treatment of these aggressive tumors.
authors.affiliation: Department of Experimental and Clinical Biomedical Sciences, University of Florence, Florence, Italy.
authors.forename: Letizia
authors.initials: L
authors.lastname: Canu
authors.affiliation: Department of Diagnostic Radiology 2, Azienda Ospedaliera-Universitaria Careggi, Florence, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Pradella
authors.affiliation: Department of Experimental and Clinical Biomedical Sciences, University of Florence, Florence, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Rapizzi
authors.affiliation: Department of Experimental and Clinical Biomedical Sciences, University of Florence, Florence, Italy.
authors.forename: Rossella
authors.initials: R
authors.lastname: Fucci
authors.affiliation: General and Surgical Unit, Azienda Ospedaliera-Universitaria Careggi, Florence, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Valeri
authors.affiliation: Division of Nuclear Medicine, Azienda Ospedaliera-Universitaria Careggi, Florence, Italy.
authors.forename: Vittorio
authors.initials: V
authors.lastname: Briganti
authors.affiliation: Department of Experimental and Clinical Biomedical Sciences, University of Florence, Florence, Italy.
authors.forename: Valentino
authors.initials: V
authors.lastname: Giachè
authors.affiliation: Endocrinology Unit, Azienda Ospedaliera-Universitaria Careggi, Florence, Italy.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Parenti
authors.affiliation: Department of Experimental and Clinical Biomedical Sciences, University of Florence, Florence, Italy.
authors.forename: Tonino
authors.initials: T
authors.lastname: Ercolino
authors.affiliation: Department of Experimental and Clinical Biomedical Sciences, University of Florence, Florence, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Mannelli
mesh_terms: D000328:Adult; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D006801:Humans; D007211:Indoles / Q000627:therapeutic use*; D008297:Male; D009154:Mutation / Q000235:genetics*; D009362:Neoplasm Metastasis; D010235:Paraganglioma / Q000098:blood supply / Q000188:drug therapy* / Q000235:genetics; D011758:Pyrroles / Q000627:therapeutic use*; D013385:Succinate Dehydrogenase / Q000235:genetics*; D000077210:Sunitinib; D016896:Treatment Outcome
chemical_list: D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D007211:Indoles; D011758:Pyrroles; C108095:SDHB protein, human; D013385:Succinate Dehydrogenase; D000077210:Sunitinib