Rationale and evidence for sunitinib in the treatment of malignant paraganglioma/pheochromocytoma.
BACKGROUND
Paragangliomas are tumors that develop from extraadrenal chromaffin cells. Approximately 20% of paragangliomas are malignant, and surgical resection is considered the primary treatment when possible. The optimal systemic treatment for advanced disease is undefined, due in part to lack of effective agents. Here we report our experience suggesting that sunitinib is an effective agent in this malignancy.


METHODS
Three patients with metastatic paraganglioma were treated with sunitinib at the Princess Margaret Hospital. Limited analyses of tumor tissue and germline DNA were available.


METHODS
Sunitinib at a standard dose (50 mg daily, 4 wk on, 2 wk off) was titrated to patient tolerance.


RESULTS
One patient has achieved a near complete response, and two patients demonstrated partial responses. Two patients demonstrated germline defects suggesting a pseudo-hypoxic drive to the tumor whereas the third demonstrated immunohistochemical evidence of this phenomenon.


CONCLUSIONS
Sunitinib appears to be an active agent in this malignancy based on this limited cohort, with an understandable mechanism of action similar to that described in other hypoxia-driven tumors. A single arm phase 2 trial is underway.
Joshua
Anthony M
AM
Department of Medical Oncology, Princess Margaret Hospital, University Health Network, 610 University Avenue, M5G 2M9 Toronto, Ontario, Canada.
Ezzat
Shereen
S
Asa
Sylvia L
SL
Evans
Andrew
A
Broom
Reuben
R
Freeman
Marc
M
Knox
Jennifer J
JJ
D000310:Adrenal Gland Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D000328:Adult; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D006801:Humans; D007211:Indoles / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010235:Paraganglioma / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D010673:Pheochromocytoma / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D011758:Pyrroles / Q000627:therapeutic use*; D000077210:Sunitinib; D014057:Tomography, X-Ray Computed
D000970:Antineoplastic Agents; D007211:Indoles; D011758:Pyrroles; D000077210:Sunitinib