Use of the tyrosine kinase inhibitor sunitinib in a patient with von Hippel-Lindau disease: targeting angiogenic factors in pheochromocytoma and other von Hippel-Lindau disease-related tumors.
BACKGROUND
von Hippel-Lindau disease is characterized by highly vascularized tumors of multiple organs.


METHODS
We present a patient with von Hippel-Lindau disease with multiple renal and pancreatic tumors and a malignant pheochromocytoma infiltrative of the sacrum and associated with lymph nodule metastases. The pheochromocytoma expressed high protein level of vascular endothelial growth factor and platelet-derived growth factor-beta receptor. The patient presented with a poor performance status, severe pelvic pain, weight loss, and manifestations of catecholamine excess.


RESULTS
Treatment against malignant pheochromocytoma with surgery, chemotherapy, or participation in clinical trials was not feasible because of the patient's poor performance status, the presence of multiple tumors, and the extension of the pheochromocytoma into the bones. Patient was treated with sunitinib, a potent tyrosine kinase inhibitor of vascular endothelial growth factor, platelet-derived growth factor, RET, c-KIT, and FLT-3 receptors. Six months of treatment with sunitinib was associated with normalization of the patient's performance status and blood pressure, absence of symptoms of catecholamine excess, weight gain, disappearance of pain, shrinkage of each of the tumors (50% in the largest renal tumor, 38% in the largest islet cell tumor, 21% in the pelvic malignant pheochromocytoma), and reduction of plasma normetanephrines and chromogranin A.


CONCLUSIONS
This study provides evidence that targeting tyrosine kinase receptors such as the vascular endothelial growth factor pathway and the platelet-derived growth factor-beta receptor may have value in the treatment of VHL-related tumors including pheochromocytoma.
Jimenez
Camilo
C
Department of Endocrine Neoplasia and Hormonal Disorders, Unit 435, The University of Texas M. D. Anderson Cancer, Center, Houston, Texas 77030, USA. cjimenez@mdanderson.org
Cabanillas
Maria E
ME
Santarpia
Libero
L
Jonasch
Eric
E
Kyle
Karen L
KL
Lano
Elizabeth A
EA
Matin
Surena F
SF
Nunez
Rodolfo F
RF
Perrier
Nancy D
ND
Phan
Alexandria
A
Rich
Thereasa A
TA
Shah
Beejal
B
Williams
Michelle D
MD
Waguespack
Steven G
SG
D000310:Adrenal Gland Neoplasms / Q000098:blood supply / Q000150:complications / Q000188:drug therapy* / Q000235:genetics; D000328:Adult; D043925:Angiogenesis Inducing Agents / Q000037:antagonists & inhibitors; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D016503:Drug Delivery Systems / Q000379:methods; D005260:Female; D006801:Humans; D007211:Indoles / Q000627:therapeutic use*; D009378:Neoplasms, Multiple Primary / Q000098:blood supply / Q000188:drug therapy* / Q000235:genetics; D010673:Pheochromocytoma / Q000098:blood supply / Q000150:complications / Q000188:drug therapy* / Q000235:genetics; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D011758:Pyrroles / Q000627:therapeutic use*; D000077210:Sunitinib; D016896:Treatment Outcome; D051794:Von Hippel-Lindau Tumor Suppressor Protein / Q000235:genetics; D006623:von Hippel-Lindau Disease / Q000150:complications / Q000188:drug therapy* / Q000235:genetics
D043925:Angiogenesis Inducing Agents; D020533:Angiogenesis Inhibitors; D007211:Indoles; D047428:Protein Kinase Inhibitors; D011758:Pyrroles; D051794:Von Hippel-Lindau Tumor Suppressor Protein; C497446:VHL protein, human; D000077210:Sunitinib