Research Papers:

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

Stéphane Oudard _, Reza Elaidi, Mara Brizard, Céline Le Rest, Valérie Caillet, Sophie Deveaux, Gérard Benoit, Jean-Michel Corréas, Farida Benoudiba, Philippe David, Alain Gaudric, Pascal Hammel, Dominique Joly, Marc Olivier Timsit, Arnaud Méjean and Stéphane Richard

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Oncotarget. 2016; 7:85306-85317. https://doi.org/10.18632/oncotarget.13301

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Stéphane Oudard1,2, Reza Elaidi3, Mara Brizard3, Céline Le Rest3, Valérie Caillet2,4, Sophie Deveaux2, Gérard Benoit2,5, Jean-Michel Corréas2,6, Farida Benoudiba2,7, Philippe David2,8, Alain Gaudric2,4, Pascal Hammel2,9, Dominique Joly2,10, Marc Olivier Timsit2,11, Arnaud Méjean2,11, Stéphane Richard2,12

 1Department of Medical Oncology, Hôpital Européen Georges Pompidou, AP-HP, Paris, France

 2Réseau Expert National pour Cancers Rares de l’Adulte PREDIR AP-HP/INCa, Hôpital Bicêtre, Le Kremlin Bicêtre, France

 3Association pour la Recherche sur les Thérapeutiques Innovantes en Cancérologie, HEGP, Paris, France

 4Department of Ophthalmology, Hôpital Lariboisière, Paris, AP-HP, France

 5Department of Urology, Hôpital Bicêtre, AP-HP, Le Kremlin-Bicêtre, France

 6Department of Radiology, Hôpital Necker, AP-HP, Paris, France

 7Department of Neuroradiology, Hôpital Bicêtre, Le Kremlin-Bicêtre, AP-HP, France

 8Department of Neurosurgery, Hôpital Bicêtre, Le Kremlin-Bicêtre, AP-HP, France

 9Department of Digestive Oncology, Hôpital Beaujon, Clichy, AP-HP, France

10Department of Nephrology, Hôpital Necker, Paris, AP-HP, France

11Department of Urology, Hôpital Européen Georges Pompidou, Paris, AP-HP, France

12Ecole 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

Correspondence to:

Stéphane Oudard, email: [email protected]

Keywords: sunitinib, von Hippel-Lindau disease, renal cell carcinoma, hemangioblastoma, toxicity

Received: September 02, 2016     Accepted: October 22, 2016     Published: November 11, 2016


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.

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