title: Paradoxical secondary polycythemia in von Hippel-Lindau patients treated with anti-vascular endothelial growth factor receptor therapy.
abstract: Von Hippel-Lindau (VHL) disease is a dominantly inherited familial cancer syndrome caused by germline mutations in the VHL tumor-suppressor gene. Central nervous system (CNS) and retinal hemangioblastomas are highly vascular tumors that are hallmarks of the disease. These tumors overexpress vascular endothelial growth factor (VEGF) and represent a potential target for anti-angiogenic drugs. We observed, after 3 to 4 months of treatment, secondary paradoxical polycythemia in 3 VHL patients with CNS or retinal hemangioblastomas treated by the anti-VEGF receptor SU5416. Hematocrit was normal before the beginning of the trial, and no progression of hemangioblastomas was observed. Polycythemia vera and all known causes of secondary polycythemia were also ruled out. Polycythemia has never been reported in current SU5416 trials for advanced malignancies and could express a specific action on red blood cell precursors occurring only in the absence of a functional VHL gene. These findings could also affect the inclusion of VHL patients with pre-existing polycythemia in future anti-VEGF receptor trials.
authors: Génétique Oncologique EPHE, UPRESS 1601, Service d'Urologie, Laboratoire d'Hématologie, CNRS UMR 8603, Hôpital Necker, Paris, France. stephane.richard@kb.u-psud.fr
authors: Stéphane
authors: S
authors: Richard
authors: Laure
authors: L
authors: Croisille
authors: Jeannine
authors: J
authors: Yvart
authors: Nicole
authors: N
authors: Casadeval
authors: Pascal
authors: P
authors: Eschwège
authors: Nozar
authors: N
authors: Aghakhani
authors: Philippe
authors: P
authors: David
authors: Alain
authors: A
authors: Gaudric
authors: Paul
authors: P
authors: Scigalla
authors: Olivier
authors: O
authors: Hermine
mesh_terms: D000328:Adult; D020533:Angiogenesis Inhibitors / Q000009:adverse effects*; D004791:Enzyme Inhibitors / Q000009:adverse effects; D005260:Female; D006400:Hematocrit; D006801:Humans; D007211:Indoles / Q000009:adverse effects*; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D011086:Polycythemia / Q000175:diagnosis / Q000209:etiology*; D011758:Pyrroles / Q000009:adverse effects*; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D017978:Receptors, Growth Factor / Q000037:antagonists & inhibitors*; D040262:Receptors, Vascular Endothelial Growth Factor; D006623:von Hippel-Lindau Disease / Q000628:therapy*
chemical_list: D020533:Angiogenesis Inhibitors; D004791:Enzyme Inhibitors; D007211:Indoles; D011758:Pyrroles; D017978:Receptors, Growth Factor; C116890:Semaxinib; D020794:Receptor Protein-Tyrosine Kinases; D040262:Receptors, Vascular Endothelial Growth Factor