Treatment with sunitinib for patients with progressive metastatic pheochromocytomas and sympathetic paragangliomas - PubMed (original) (raw)

. 2012 Nov;97(11):4040-50.

doi: 10.1210/jc.2012-2356. Epub 2012 Sep 10.

Cecile N Chougnet, Mouhammed Amir Habra, J Lynn Palmer, Sophie Leboulleux, Maria E Cabanillas, Caroline Caramella, Pete Anderson, Abir Al Ghuzlan, Steven G Waguespack, Desirée Deandreis, Eric Baudin, Camilo Jimenez

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

Montserrat Ayala-Ramirez et al. J Clin Endocrinol Metab. 2012 Nov.

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.

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Figures

Fig. 1.

Fig. 1.

Median overall survival from sunitinib initiation.

Fig. 2.

Fig. 2.

PFS in patients with progressive metastatic PHEO or SPGL treated with sunitinib.

Fig. 3.

Fig. 3.

Positive response to sunitinib and rapamycin. A patient with both bone and soft-tissue sites of metastatic disease was treated with sunitinib. The results of two FDG-PET/CT studies are shown, obtained 36 months apart. A and B, A soft-tissue metastasis in the right flank decreased in intensity from an SUV of 17.5 before treatment to 2.7 after treatment; C and D, a lytic bone metastasis in the T11 vertebral body decreased in intensity from an SUV of 21.6 to 2.1; E and F, a lytic bone metastasis in the right iliac bone, although persistently hypermetabolic, showed positive response with a decline in SUV from 37.6–14.6.

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