Phase II study of belinostat in patients with recurrent or refractory advanced thymic epithelial tumors

Giuseppe Giaccone, Arun Rajan, Arlene Berman, Ronan J. Kelly, Eva Szabo, Ariel Lopez-Chavez, Jane Trepel, Min Jung Lee, Liang Cao, Igor Espinoza-Delgado, John Spittler, Patrick Loehrer

Research output: Contribution to journalArticle

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Abstract

Purpose: Thymic epithelial tumors are rare malignancies, and there is no standard treatment for patients with advanced disease in whom chemotherapy has failed. Antitumor activity of histone deacetylase (HDAC) inhibitors in this disease has been documented, including one patient with thymoma treated with the pan-HDAC inhibitor belinostat. Patients and Methods: Patients with advanced thymic epithelial malignancies in whom at least one line of platinum-containing chemotherapy had failed were eligible for this study. Other eligibility criteria included adequate organ function and good performance status. Belinostat was administered intravenously at 1 g/m2 on days 1 to 5 of a 21-day cycle until disease progression or development of intolerance. The primary objective was response rate in patients with thymoma. Results: Of the 41 patients enrolled, 25 had thymoma, and 16 had thymic carcinoma; patients had a median of two previous systemic regimens (range, one to 10 regimens). Treatment was well tolerated, with nausea, vomiting, and fatigue being the most frequent adverse effects. Two patients achieved partial response (both had thymoma; response rate, 8%; 95% CI, 2.2% to 25%), 25 had stable disease, and 13 had progressive disease; there were no responses among patients with thymic carcinoma. Median times to progression and survival were 5.8 and 19.1 months, respectively. Survival of patients with thymoma was significantly longer than that of patients with thymic carcinoma (median not reached v 12.4 months; P = .001). Protein acetylation, regulatory T-cell numbers, and circulating angiogenic factors did not predict outcome. Conclusion: Belinostat has modest antitumor activity in this group of heavily pretreated thymic malignancies. However, the duration of response and disease stabilization is intriguing, and additional testing of belinostat in this disease is warranted.

Original languageEnglish
Pages (from-to)2052-2059
Number of pages8
JournalJournal of Clinical Oncology
Volume29
Issue number15
DOIs
StatePublished - May 20 2011

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Thymoma
Histone Deacetylase Inhibitors
belinostat
Thymic epithelial tumor
Drug Therapy
Neoplasms
Survival
Angiogenesis Inducing Agents
Regulatory T-Lymphocytes
Acetylation
Platinum
Nausea
Vomiting
Fatigue
Disease Progression
Cell Count
Therapeutics

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Phase II study of belinostat in patients with recurrent or refractory advanced thymic epithelial tumors. / Giaccone, Giuseppe; Rajan, Arun; Berman, Arlene; Kelly, Ronan J.; Szabo, Eva; Lopez-Chavez, Ariel; Trepel, Jane; Lee, Min Jung; Cao, Liang; Espinoza-Delgado, Igor; Spittler, John; Loehrer, Patrick.

In: Journal of Clinical Oncology, Vol. 29, No. 15, 20.05.2011, p. 2052-2059.

Research output: Contribution to journalArticle

Giaccone, G, Rajan, A, Berman, A, Kelly, RJ, Szabo, E, Lopez-Chavez, A, Trepel, J, Lee, MJ, Cao, L, Espinoza-Delgado, I, Spittler, J & Loehrer, P 2011, 'Phase II study of belinostat in patients with recurrent or refractory advanced thymic epithelial tumors', Journal of Clinical Oncology, vol. 29, no. 15, pp. 2052-2059. https://doi.org/10.1200/JCO.2010.32.4467
Giaccone, Giuseppe ; Rajan, Arun ; Berman, Arlene ; Kelly, Ronan J. ; Szabo, Eva ; Lopez-Chavez, Ariel ; Trepel, Jane ; Lee, Min Jung ; Cao, Liang ; Espinoza-Delgado, Igor ; Spittler, John ; Loehrer, Patrick. / Phase II study of belinostat in patients with recurrent or refractory advanced thymic epithelial tumors. In: Journal of Clinical Oncology. 2011 ; Vol. 29, No. 15. pp. 2052-2059.
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AU - Rajan, Arun

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AU - Kelly, Ronan J.

AU - Szabo, Eva

AU - Lopez-Chavez, Ariel

AU - Trepel, Jane

AU - Lee, Min Jung

AU - Cao, Liang

AU - Espinoza-Delgado, Igor

AU - Spittler, John

AU - Loehrer, Patrick

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N2 - Purpose: Thymic epithelial tumors are rare malignancies, and there is no standard treatment for patients with advanced disease in whom chemotherapy has failed. Antitumor activity of histone deacetylase (HDAC) inhibitors in this disease has been documented, including one patient with thymoma treated with the pan-HDAC inhibitor belinostat. Patients and Methods: Patients with advanced thymic epithelial malignancies in whom at least one line of platinum-containing chemotherapy had failed were eligible for this study. Other eligibility criteria included adequate organ function and good performance status. Belinostat was administered intravenously at 1 g/m2 on days 1 to 5 of a 21-day cycle until disease progression or development of intolerance. The primary objective was response rate in patients with thymoma. Results: Of the 41 patients enrolled, 25 had thymoma, and 16 had thymic carcinoma; patients had a median of two previous systemic regimens (range, one to 10 regimens). Treatment was well tolerated, with nausea, vomiting, and fatigue being the most frequent adverse effects. Two patients achieved partial response (both had thymoma; response rate, 8%; 95% CI, 2.2% to 25%), 25 had stable disease, and 13 had progressive disease; there were no responses among patients with thymic carcinoma. Median times to progression and survival were 5.8 and 19.1 months, respectively. Survival of patients with thymoma was significantly longer than that of patients with thymic carcinoma (median not reached v 12.4 months; P = .001). Protein acetylation, regulatory T-cell numbers, and circulating angiogenic factors did not predict outcome. Conclusion: Belinostat has modest antitumor activity in this group of heavily pretreated thymic malignancies. However, the duration of response and disease stabilization is intriguing, and additional testing of belinostat in this disease is warranted.

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