Treatment with Sunitinib for Patients with Progressive Metastatic Pheochromocytomas and Sympathetic Paragangliomas
Open Access
- 1 November 2012
- journal article
- other
- Published by The Endocrine Society in Journal of Clinical Endocrinology & Metabolism
- Vol. 97 (11), 4040-4050
- https://doi.org/10.1210/jc.2012-2356
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 [18F]fluorodeoxyglucose/computed tomography ([18F]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 [18F]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 [18F]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.This publication has 34 references indexed in Scilit:
- Phase 1 trial of everolimus plus sunitinib in patients with metastatic renal cell carcinomaCancer, 2011
- Integrative genomic analysis reveals somatic mutations in pheochromocytoma and paragangliomaHuman Molecular Genetics, 2011
- Hypertension as a Biomarker of Efficacy in Patients With Metastatic Renal Cell Carcinoma Treated With SunitinibJNCI Journal of the National Cancer Institute, 2011
- Phase II Study of High-Dose [131I]Metaiodobenzylguanidine Therapy for Patients With Metastatic Pheochromocytoma and ParagangliomaJournal of Clinical Oncology, 2009
- Novel and Evolving Therapies in the Treatment of Malignant Phaeochromocytoma: Experience with the mTOR Inhibitor Everolimus (RAD001)Hormone and Metabolic Research, 2009
- From RECIST to PERCIST: Evolving Considerations for PET Response Criteria in Solid TumorsJournal of Nuclear Medicine, 2009
- Sunitinib, a Novel Therapy for Anthracycline- and Cisplatin-refractory Malignant PheochromocytomaJapanese Journal of Clinical Oncology, 2009
- New response evaluation criteria in solid tumours: Revised RECIST guideline (version 1.1)European Journal of Cancer, 2009
- The Role of Mammalian Target of Rapamycin Inhibitors in the Treatment of Advanced Renal CancerClinical Cancer Research, 2007
- A HIF1α Regulatory Loop Links Hypoxia and Mitochondrial Signals in PheochromocytomasPLoS Genetics, 2005