Phase II trial of pazopanib in advanced/progressive malignant pheochromocytoma and paraganglioma

Sina Jasim, Vera Jean Suman, Camilo Jimenez, Pamela Harris, Kostandinos Sideras, Jill K. Burton, Francis Paul Worden, Richard J. Auchus, Keith C. Bible

Research output: Contribution to journalArticle

13 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)220-225
Number of pages6
JournalEndocrine
Volume57
Issue number2
DOIs
StatePublished - Aug 1 2017

Fingerprint

Paraganglioma
Pheochromocytoma
Takotsubo Cardiomyopathy
Hypertension
Fatigue
Headache
Disease Progression
Neoplasms
Growth Factor Receptors
Vascular Endothelium
Hematuria
Cardiomyopathies
Terminology
Disease-Free Survival
Blood Vessels
pazopanib
Diarrhea
Phosphotransferases
Therapeutics
Survival

Keywords

  • Metastatic
  • Paraganglioma
  • Pazopanib
  • Takotsubo cardiomyopathy

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

Cite this

Jasim, S., Suman, V. J., Jimenez, C., Harris, P., Sideras, K., Burton, J. K., ... Bible, K. C. (2017). Phase II trial of pazopanib in advanced/progressive malignant pheochromocytoma and paraganglioma. Endocrine, 57(2), 220-225. https://doi.org/10.1007/s12020-017-1359-5

Phase II trial of pazopanib in advanced/progressive malignant pheochromocytoma and paraganglioma. / Jasim, Sina; Suman, Vera Jean; Jimenez, Camilo; Harris, Pamela; Sideras, Kostandinos; Burton, Jill K.; Worden, Francis Paul; Auchus, Richard J.; Bible, Keith C.

In: Endocrine, Vol. 57, No. 2, 01.08.2017, p. 220-225.

Research output: Contribution to journalArticle

Jasim, S, Suman, VJ, Jimenez, C, Harris, P, Sideras, K, Burton, JK, Worden, FP, Auchus, RJ & Bible, KC 2017, 'Phase II trial of pazopanib in advanced/progressive malignant pheochromocytoma and paraganglioma', Endocrine, vol. 57, no. 2, pp. 220-225. https://doi.org/10.1007/s12020-017-1359-5
Jasim, Sina ; Suman, Vera Jean ; Jimenez, Camilo ; Harris, Pamela ; Sideras, Kostandinos ; Burton, Jill K. ; Worden, Francis Paul ; Auchus, Richard J. ; Bible, Keith C. / Phase II trial of pazopanib in advanced/progressive malignant pheochromocytoma and paraganglioma. In: Endocrine. 2017 ; Vol. 57, No. 2. pp. 220-225.
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