title: Sunitinib for the treatment of benign and malignant neoplasms from von Hippel-Lindau disease: A single-arm, prospective phase II clinical study from the PREDIR group.
abstract: Von Hippel-Lindau (VHL) disease is an autosomal dominant hereditary cancer syndrome that predisposes affected individuals to the development of multiple benign and malignant tumors. One of the main manifestations of VHL is renal cell carcinoma (RCC). RCC is increasingly being treated with targeted therapies, which offer an alternative treatment option for patients with VHL disease. This study investigated the effectiveness of sunitinib in VHL patients with advanced tumors or tumors unsuitable for surgery.This multicenter, phase II, open-label study from the PREDIR VHL network, treated patients with genetically-confirmed advanced VHL disease with oral sunitinib (50 mg/day for 28 days then a 2-week rest period) until progression. Lesions were performed using magnetic resonance imaging (MRI) and computed tomographic (CT) scan. The primary endpoint was objective response rate; secondary endpoints included tolerability and overall survival.All five patients showed stable disease as best response at 6 months. Two patients showed impressive transitory clinical improvement during early cycles. No patient died during sunitinib treatment. Reasons for discontinuing sunitinib therapy were disease progression (n=1), unacceptable toxicity (n=3) and lack of clinical improvement after 7 cycles (10.5 months) with unacceptable toxicity (n=1).In conclusion, sunitinib was of limited benefit in patients with advanced VHL disease, but had better efficacy against metastatic RCC than other VHL-related lesions. Treatment-related toxicity is an important limiting factor in this frail patient population. New agents with different mechanisms of action are required to treat this disease.
authors.affiliation: Department of Nephrology, Hôpital Necker, Paris, AP-HP, France.|Department of Urology, Hôpital Européen Georges Pompidou, Paris, AP-HP, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Oudard
authors.affiliation: Ecole Pratique des Hautes Etudes, Paris, France Laboratoire de Génétique Oncologique EPHE, INSERM, Villejuif, France and Faculté de Médecine Université Paris-Sud, Le Kremlin-Bicêtre, France.
authors.forename: Reza
authors.initials: R
authors.lastname: Elaidi
authors.affiliation: Ecole Pratique des Hautes Etudes, Paris, France Laboratoire de Génétique Oncologique EPHE, INSERM, Villejuif, France and Faculté de Médecine Université Paris-Sud, Le Kremlin-Bicêtre, France.
authors.forename: Mara
authors.initials: M
authors.lastname: Brizard
authors.affiliation: Ecole Pratique des Hautes Etudes, Paris, France Laboratoire de Génétique Oncologique EPHE, INSERM, Villejuif, France and Faculté de Médecine Université Paris-Sud, Le Kremlin-Bicêtre, France.
authors.forename: Céline
authors.initials: C
authors.lastname: Le Rest
authors.affiliation: Department of Urology, Hôpital Européen Georges Pompidou, Paris, AP-HP, France.
authors.forename: Valérie
authors.initials: V
authors.lastname: Caillet
authors.affiliation: Department of Urology, Hôpital Européen Georges Pompidou, Paris, AP-HP, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Deveaux
authors.affiliation: Department of Urology, Hôpital Européen Georges Pompidou, Paris, AP-HP, France.
authors.forename: Gérard
authors.initials: G
authors.lastname: Benoit
authors.affiliation: Department of Urology, Hôpital Européen Georges Pompidou, Paris, AP-HP, France.
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Corréas
authors.affiliation: Department of Urology, Hôpital Européen Georges Pompidou, Paris, AP-HP, France.
authors.forename: Farida
authors.initials: F
authors.lastname: Benoudiba
authors.affiliation: Department of Urology, Hôpital Européen Georges Pompidou, Paris, AP-HP, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: David
authors.affiliation: Department of Urology, Hôpital Européen Georges Pompidou, Paris, AP-HP, France.
authors.forename: Alain
authors.initials: A
authors.lastname: Gaudric
authors.affiliation: Department of Urology, Hôpital Européen Georges Pompidou, Paris, AP-HP, France.
authors.forename: Pascal
authors.initials: P
authors.lastname: Hammel
authors.affiliation: Department of Urology, Hôpital Européen Georges Pompidou, Paris, AP-HP, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Joly
authors.affiliation: Department of Urology, Hôpital Européen Georges Pompidou, Paris, AP-HP, France.
authors.forename: Marc Olivier
authors.initials: MO
authors.lastname: Timsit
authors.affiliation: Department of Urology, Hôpital Européen Georges Pompidou, Paris, AP-HP, France.
authors.forename: Arnaud
authors.initials: A
authors.lastname: Méjean
authors.affiliation: Department of Urology, Hôpital Européen Georges Pompidou, Paris, AP-HP, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Richard
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000209:etiology / Q000401:mortality; D005260:Female; D005602:France; D006801:Humans; D007211:Indoles / Q000627:therapeutic use*; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000209:etiology / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D009369:Neoplasms / Q000188:drug therapy* / Q000209:etiology / Q000401:mortality; D011446:Prospective Studies; D011758:Pyrroles / Q000627:therapeutic use*; D000077210:Sunitinib; D016019:Survival Analysis; D016896:Treatment Outcome; D006623:von Hippel-Lindau Disease / Q000150:complications / Q000188:drug therapy* / Q000401:mortality
chemical_list: D000970:Antineoplastic Agents; D007211:Indoles; D011758:Pyrroles; D000077210:Sunitinib
keywords: hemangioblastoma; renal cell carcinoma; sunitinib; toxicity; von Hippel-Lindau disease