Abstract
Introduction
Pheochromocytomas and paragangliomas (Pheo/PGL) are rare, vascular, sometimes malignant endocrine tumors. Case reports indicate the activity of vascular endothelium growth factor receptor-targeted kinase inhibitors in these cancers.
Objectives
To assess the antitumor activity and tolerability of pazopanib in progressive malignant Pheo/PGL.
Patients and methods
This multicenter Phase II trial (MC107C) enrolled individuals ≥18 years old with disease progression ≤ 6 months prior to registration, Eastern Cooperative Oncology Group PS 0–2, and measurable disease (response evaluation criteria in solid tumors 1.0). Pazopanib was administered in 28-day cycles, with the regimen ultimately being as follows: cycle 1: 400 mg daily on days 1–14, cycle 2: 800 mg daily on days 1–14, and then cycle 2 + : 800 mg daily on all days.
Results
The study was halted due to poor accrual. Seven patients were enrolled (05/2011–11/2014). One patient withdrew consent prior to treatment, leaving six evaluable patients. Treatment was discontinued, due to the following reasons: disease progression (4); withdrawal (1); and grade 4 (Takotsubo) cardiomyopathy (1). The median number of cycles administered was 4 (range: 2–29, total: 49). Four patients had >1 dose reduction due to the following reasons: fatigue (1), abnormal liver tests (2), hypertension and (Takotsubo) cardiomyopathy (1), and headaches (1). Common severe (Common Terminology Criteria for Adverse Events v3.0 grades 3–5) toxicities were as follows: hypertension (3/6), (Takotsubo) cardiomyopathy (2/6), diarrhea (1/6), fatigue (1/6), headache (1/6), and hematuria (1/6). One confirmed partial response was observed in PGL (17%, duration 2.4 years); median progression-free survival and overall survival were 6.5 and 14.8 months, respectively.
Conclusion
Pazopanib has activity in Pheo/PGL requiring more study; optimal alpha- and beta-blockade are imperative pre-therapy in patients with secretory tumors, as risk of hypertension and cardiomyopathy are potentially life threatening.
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Acknowledgements
Research reported in this publication was supported by the National Cancer Institute of the National Institutes of Health under Award Number P30CA046592. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. We thank Elizabeth Hesseltine, NP, University of Michigan Comprehensive Cancer Center, for the help in data collection. This work was supported in part by NCI CA15083 and CM62205.
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Jasim, S., Suman, V.J., Jimenez, C. et al. Phase II trial of pazopanib in advanced/progressive malignant pheochromocytoma and paraganglioma. Endocrine 57, 220–225 (2017). https://doi.org/10.1007/s12020-017-1359-5
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DOI: https://doi.org/10.1007/s12020-017-1359-5