Treatment with sunitinib for patients with progressive metastatic pheochromocytomas and sympathetic paragangliomas

J Clin Endocrinol Metab. 2012 Nov;97(11):4040-50. doi: 10.1210/jc.2012-2356. Epub 2012 Sep 10.

Abstract

Context: Patients with progressive metastatic pheochromocytomas (PHEOs) or sympathetic paragangliomas (SPGLs) face a dismal prognosis. Current systemic therapies are limited.

Objectives: The primary end point was progression-free survival determined by RECIST 1.1 criteria or positron emission tomography with [(18)F]fluorodeoxyglucose/computed tomography ([(18)F]FDG-PET/CT), in the absence of measurable soft tissue targets. Secondary endpoints were tumor response according to RECIST criteria version 1.1 or FDG uptake, blood pressure control, and safety.

Design: We conducted a retrospective review of medical records of patients with metastatic PHEO/SPGL treated with sunitinib from December 2007 through December 2011. An intention-to-treat analysis was performed.

Patients and setting: Seventeen patients with progressive metastatic PHEO/SPGLs treated at the Institut Gustave-Roussy and MD Anderson Cancer Center.

Interventions: Patients treated with sunitinib.

Results: According to RECIST 1.1, eight patients experienced clinical benefit; three experienced partial response, and five had stable disease, including four with predominant skeletal metastases that showed a 30% or greater reduction in glucose uptake on [(18)F]FDG-PET/CT. Of 14 patients who had hypertension, six became normotensive and two discontinued antihypertensives. One patient treated with sunitinib and rapamycin experienced a durable benefit beyond 36 months. The median overall survival from the time sunitinib was initiated was 26.7 months with a progression-free survival of 4.1 months (95% confidence interval = 1.4-11.0). Most patients who experienced a clinical benefit were carriers of SDHB mutations.

Conclusion: Sunitinib is associated with tumor size reduction, decreased [(18)F]FDG-PET/CT uptake, disease stabilization, and hypertension improvement in some patients with progressive metastatic PHEO/PGL. Prospective multi-institutional clinical trials are needed to determine the true benefits of sunitinib.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Adrenal Gland Neoplasms / diagnosis
  • Adrenal Gland Neoplasms / drug therapy*
  • Adrenal Gland Neoplasms / pathology
  • Adult
  • Aged
  • Antineoplastic Agents / therapeutic use*
  • Disease-Free Survival
  • Female
  • Humans
  • Indoles / therapeutic use*
  • Male
  • Middle Aged
  • Paraganglioma / diagnosis
  • Paraganglioma / drug therapy*
  • Paraganglioma / secondary
  • Pheochromocytoma / diagnosis
  • Pheochromocytoma / drug therapy*
  • Pheochromocytoma / secondary
  • Pyrroles / therapeutic use*
  • Retrospective Studies
  • Sunitinib
  • Treatment Outcome

Substances

  • Antineoplastic Agents
  • Indoles
  • Pyrroles
  • Sunitinib