A multicenter phase 2 trial of pazopanib in metastatic and progressive medullary thyroid carcinoma

MC057H

Keith C. Bible, Vera Jean Suman, Julian R Molina, Robert Christian Smallridge, William J. Maples, Michael E. Menefee, Joseph Rubin, Nina Karlin, Kostandinos Sideras, John C. Morris, Bryan McIver, Ian D Hay, Vahab Fatourechi, Jill K. Burton, Kevin P. Webster, Carolyn Bieber, Anne M. Traynor, Patrick J. Flynn, Boon Cher Goh, Crescent R. Isham & 2 others Pamela Harris, Charles Erlichman

Research output: Contribution to journalArticle

49 Citations (Scopus)

Abstract

Context: Pazopanib is a small molecule inhibitor of kinases principally including vascular endothelial growth factor receptors-1, -2, and -3; platelet-derived growth factor receptors-α and -β; and c-Kit. We previously reported a tumor response rate of 49% in patients with advanced differentiated thyroid cancer and 0% in patients with advanced anaplastic thyroid cancer. The present report details results of pazopanib therapy in advanced medullary thyroid cancer (MTC). Objective, Design, Setting, Patients, Intervention, and Outcome Measures: Having noted preclinical activity of pazopanib in MTC, patients with advanced MTC who had disease progression within the preceding 6 months were accrued to this multiinstitutional phase II clinical trial to assess tumor response rate (by Response Evaluation Criteria In Solid Tumors criteria) and safety of pazopanib given orally once daily at 800 mg until disease progression or intolerability. Results: From September 22, 2008, to December 11, 2011, 35 individuals (80% males, median age 60 y) were enrolled. All patients have been followed up until treatment discontinuation or for a minimum of four cycles. Eight patients (23%) are still on the study treatment. The median number of therapy cycles was eight. Five patients attained partial Response Evaluation Criteria In Solid Tumors responses (14.3%; 90% confidence interval 5.8%-27.7%), with a median progression-free survival and overall survival of 9.4 and 19.9 months, respectively. Side effects included treatmentrequiring (new) hypertension (33%), fatigue (14%), diarrhea (9%), and abnormal liver tests (6%); 3 of 35 patients (8.6%) discontinued therapy due to adverse events. There was one death of a study patient after withdrawal from the trial deemed potentially treatment related. Conclusions: Pazopanib has promising clinical activity in metastatic MTC with overall manageable toxicities.

Original languageEnglish (US)
Pages (from-to)1687-1693
Number of pages7
JournalJournal of Clinical Endocrinology and Metabolism
Volume99
Issue number5
DOIs
StatePublished - 2014

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Tumors
Vascular Endothelial Growth Factor Receptor-1
Platelet-Derived Growth Factor Receptors
Disease Progression
Liver
Toxicity
Therapeutics
Phosphotransferases
Medullary Thyroid cancer
pazopanib
Fatigue of materials
Vascular Endothelial Growth Factor Receptor-2
Phase II Clinical Trials
Molecules
Thyroid Neoplasms
Disease-Free Survival
Fatigue
Diarrhea
Neoplasms
Outcome Assessment (Health Care)

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Endocrinology
  • Biochemistry, medical
  • Endocrinology, Diabetes and Metabolism

Cite this

A multicenter phase 2 trial of pazopanib in metastatic and progressive medullary thyroid carcinoma : MC057H. / Bible, Keith C.; Suman, Vera Jean; Molina, Julian R; Smallridge, Robert Christian; Maples, William J.; Menefee, Michael E.; Rubin, Joseph; Karlin, Nina; Sideras, Kostandinos; Morris, John C.; McIver, Bryan; Hay, Ian D; Fatourechi, Vahab; Burton, Jill K.; Webster, Kevin P.; Bieber, Carolyn; Traynor, Anne M.; Flynn, Patrick J.; Goh, Boon Cher; Isham, Crescent R.; Harris, Pamela; Erlichman, Charles.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 99, No. 5, 2014, p. 1687-1693.

Research output: Contribution to journalArticle

Bible, KC, Suman, VJ, Molina, JR, Smallridge, RC, Maples, WJ, Menefee, ME, Rubin, J, Karlin, N, Sideras, K, Morris, JC, McIver, B, Hay, ID, Fatourechi, V, Burton, JK, Webster, KP, Bieber, C, Traynor, AM, Flynn, PJ, Goh, BC, Isham, CR, Harris, P & Erlichman, C 2014, 'A multicenter phase 2 trial of pazopanib in metastatic and progressive medullary thyroid carcinoma: MC057H', Journal of Clinical Endocrinology and Metabolism, vol. 99, no. 5, pp. 1687-1693. https://doi.org/10.1210/jc.2013-3713
Bible, Keith C. ; Suman, Vera Jean ; Molina, Julian R ; Smallridge, Robert Christian ; Maples, William J. ; Menefee, Michael E. ; Rubin, Joseph ; Karlin, Nina ; Sideras, Kostandinos ; Morris, John C. ; McIver, Bryan ; Hay, Ian D ; Fatourechi, Vahab ; Burton, Jill K. ; Webster, Kevin P. ; Bieber, Carolyn ; Traynor, Anne M. ; Flynn, Patrick J. ; Goh, Boon Cher ; Isham, Crescent R. ; Harris, Pamela ; Erlichman, Charles. / A multicenter phase 2 trial of pazopanib in metastatic and progressive medullary thyroid carcinoma : MC057H. In: Journal of Clinical Endocrinology and Metabolism. 2014 ; Vol. 99, No. 5. pp. 1687-1693.
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abstract = "Context: Pazopanib is a small molecule inhibitor of kinases principally including vascular endothelial growth factor receptors-1, -2, and -3; platelet-derived growth factor receptors-α and -β; and c-Kit. We previously reported a tumor response rate of 49{\%} in patients with advanced differentiated thyroid cancer and 0{\%} in patients with advanced anaplastic thyroid cancer. The present report details results of pazopanib therapy in advanced medullary thyroid cancer (MTC). Objective, Design, Setting, Patients, Intervention, and Outcome Measures: Having noted preclinical activity of pazopanib in MTC, patients with advanced MTC who had disease progression within the preceding 6 months were accrued to this multiinstitutional phase II clinical trial to assess tumor response rate (by Response Evaluation Criteria In Solid Tumors criteria) and safety of pazopanib given orally once daily at 800 mg until disease progression or intolerability. Results: From September 22, 2008, to December 11, 2011, 35 individuals (80{\%} males, median age 60 y) were enrolled. All patients have been followed up until treatment discontinuation or for a minimum of four cycles. Eight patients (23{\%}) are still on the study treatment. The median number of therapy cycles was eight. Five patients attained partial Response Evaluation Criteria In Solid Tumors responses (14.3{\%}; 90{\%} confidence interval 5.8{\%}-27.7{\%}), with a median progression-free survival and overall survival of 9.4 and 19.9 months, respectively. Side effects included treatmentrequiring (new) hypertension (33{\%}), fatigue (14{\%}), diarrhea (9{\%}), and abnormal liver tests (6{\%}); 3 of 35 patients (8.6{\%}) discontinued therapy due to adverse events. There was one death of a study patient after withdrawal from the trial deemed potentially treatment related. Conclusions: Pazopanib has promising clinical activity in metastatic MTC with overall manageable toxicities.",
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T1 - A multicenter phase 2 trial of pazopanib in metastatic and progressive medullary thyroid carcinoma

T2 - MC057H

AU - Bible, Keith C.

AU - Suman, Vera Jean

AU - Molina, Julian R

AU - Smallridge, Robert Christian

AU - Maples, William J.

AU - Menefee, Michael E.

AU - Rubin, Joseph

AU - Karlin, Nina

AU - Sideras, Kostandinos

AU - Morris, John C.

AU - McIver, Bryan

AU - Hay, Ian D

AU - Fatourechi, Vahab

AU - Burton, Jill K.

AU - Webster, Kevin P.

AU - Bieber, Carolyn

AU - Traynor, Anne M.

AU - Flynn, Patrick J.

AU - Goh, Boon Cher

AU - Isham, Crescent R.

AU - Harris, Pamela

AU - Erlichman, Charles

PY - 2014

Y1 - 2014

N2 - Context: Pazopanib is a small molecule inhibitor of kinases principally including vascular endothelial growth factor receptors-1, -2, and -3; platelet-derived growth factor receptors-α and -β; and c-Kit. We previously reported a tumor response rate of 49% in patients with advanced differentiated thyroid cancer and 0% in patients with advanced anaplastic thyroid cancer. The present report details results of pazopanib therapy in advanced medullary thyroid cancer (MTC). Objective, Design, Setting, Patients, Intervention, and Outcome Measures: Having noted preclinical activity of pazopanib in MTC, patients with advanced MTC who had disease progression within the preceding 6 months were accrued to this multiinstitutional phase II clinical trial to assess tumor response rate (by Response Evaluation Criteria In Solid Tumors criteria) and safety of pazopanib given orally once daily at 800 mg until disease progression or intolerability. Results: From September 22, 2008, to December 11, 2011, 35 individuals (80% males, median age 60 y) were enrolled. All patients have been followed up until treatment discontinuation or for a minimum of four cycles. Eight patients (23%) are still on the study treatment. The median number of therapy cycles was eight. Five patients attained partial Response Evaluation Criteria In Solid Tumors responses (14.3%; 90% confidence interval 5.8%-27.7%), with a median progression-free survival and overall survival of 9.4 and 19.9 months, respectively. Side effects included treatmentrequiring (new) hypertension (33%), fatigue (14%), diarrhea (9%), and abnormal liver tests (6%); 3 of 35 patients (8.6%) discontinued therapy due to adverse events. There was one death of a study patient after withdrawal from the trial deemed potentially treatment related. Conclusions: Pazopanib has promising clinical activity in metastatic MTC with overall manageable toxicities.

AB - Context: Pazopanib is a small molecule inhibitor of kinases principally including vascular endothelial growth factor receptors-1, -2, and -3; platelet-derived growth factor receptors-α and -β; and c-Kit. We previously reported a tumor response rate of 49% in patients with advanced differentiated thyroid cancer and 0% in patients with advanced anaplastic thyroid cancer. The present report details results of pazopanib therapy in advanced medullary thyroid cancer (MTC). Objective, Design, Setting, Patients, Intervention, and Outcome Measures: Having noted preclinical activity of pazopanib in MTC, patients with advanced MTC who had disease progression within the preceding 6 months were accrued to this multiinstitutional phase II clinical trial to assess tumor response rate (by Response Evaluation Criteria In Solid Tumors criteria) and safety of pazopanib given orally once daily at 800 mg until disease progression or intolerability. Results: From September 22, 2008, to December 11, 2011, 35 individuals (80% males, median age 60 y) were enrolled. All patients have been followed up until treatment discontinuation or for a minimum of four cycles. Eight patients (23%) are still on the study treatment. The median number of therapy cycles was eight. Five patients attained partial Response Evaluation Criteria In Solid Tumors responses (14.3%; 90% confidence interval 5.8%-27.7%), with a median progression-free survival and overall survival of 9.4 and 19.9 months, respectively. Side effects included treatmentrequiring (new) hypertension (33%), fatigue (14%), diarrhea (9%), and abnormal liver tests (6%); 3 of 35 patients (8.6%) discontinued therapy due to adverse events. There was one death of a study patient after withdrawal from the trial deemed potentially treatment related. Conclusions: Pazopanib has promising clinical activity in metastatic MTC with overall manageable toxicities.

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DO - 10.1210/jc.2013-3713

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