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.
Oncotarget. 2016 Nov 11 [Epub ahead of print]
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, Stéphane Richard
Department of Nephrology, Hôpital Necker, Paris, AP-HP, France., 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., Department of Urology, Hôpital Européen Georges Pompidou, Paris, AP-HP, France.