Pilot study of dovitinib in patients with von Hippel-Lindau disease
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Patrick Pilié1, Elshad Hasanov2, Surena F. Matin3, Ashley H. Henriksen Woodson4, Valerie D. Marcott1, Shelly Bird1, Rebecca S. Slack5, Gregory N. Fuller6, Ian E. McCutcheon7 and Eric Jonasch1
1Department of Genitourinary Medical Oncology, Division of Cancer Medicine, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
2Department of Internal Medicine, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX 77030, USA
3Department of Urology, Division of Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
4Department of Clinical Cancer Genetics, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
5Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
6Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
7Department of Neurosurgery, Division of Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
Eric Jonasch, email: [email protected]
Keywords: von Hippel-Lindau; hemangioblastomas; tyrosine kinase inhibitor; dovitinib; fibroblast growth factor receptor
Received: November 30, 2017 Accepted: April 04, 2018 Published: May 04, 2018
Von Hippel-Lindau (VHL) disease is an autosomal dominant disease occurring in 1 in 35,000 births and leads to an increased risk of a phenotypically diverse array of tumor types including, but not limited to, clear cell renal cell carcinoma (ccRCC) and hemangioblastomas (HBs). Previous studies of patients with VHL disease treated with the tyrosine kinase inhibitor (TKI) sunitinib did not show clinical response in HBs. Interestingly, VHL-related HBs displayed increased fibroblast growth factor receptor 3 (FGFR3) protein expression when compared to VHL-related ccRCCs. Therefore, in this pilot study, we assessed the safety and efficacy profile of TKI 258 (dovitinib), a multi-tyrosine kinase inhibitor of VEGF receptor and fibroblast growth factor (FGF), in patients with VHL disease who had measureable HBs. The trial was stopped after six patients enrolled after the toxicity stopping rule was triggered. With regards to safety, 6/6 subjects had at least one adverse event (AE). Best response in 6/6 subjects was stable disease (SD) in HBs. While the negative safety and efficacy results of this pilot study do not favor the use of dovitinib for the treatment of asymptomatic HBs in VHL disease patients, further investigation into alternative scheduling and other FGFR inhibitors for the treatment of HBs in VHL disease patients is warranted given the promising pre-clinical and molecular data.
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