Phase II trial of single agent amrubicin in patients with previously treated advanced thymic malignancies

Jessica A. Hellyer, Matthew A. Gubens, Kristen M. Cunanan, Sukhmani K. Padda, Matthew Burns, A. John Spittler, Jonathan W. Riess, Melanie San Pedro-Salcedo, Kavitha J. Ramchandran, Joel W. Neal, Heather A. Wakelee, Patrick J. Loehrer

Research output: Contribution to journalArticle

Abstract

Objectives: There are limited treatment options for patients with thymic malignancies. Here we present data supporting treatment with single agent amrubicin, a third generation anthracycline and topoisomerase II inhibitor. Materials and methods: This was a phase 2 open-label, single arm trial of amrubicin in patients with thymoma (T) or thymic carcinoma (TC), conducted at two academic institutions. Patients were included if they had received at least one prior chemotherapy regimen. The first 18 patients received amrubicin at 40 mg/m2 IV days 1–3 repeated every 3-weeks. Due to the high incidence of febrile neutropenia, dosing was subsequently amended to 35 mg/m2 for the final 15 patients. Results: A total of 33 patients (14 T/19 TC) were enrolled from 2011 to 2014. Median number of prior therapies was 2. Best response included 6 partial responses, 21 stable disease, and 6 progressive disease (all TC). Objective response rate was 18% (90% exact binomial CI 8.2%–32.8%; T = 4/14 (29%), TC = 2/19 (11%)). Median progression-free survival was 7.7 months (T: 8.3 months; TC: 7.3) and median overall survival was 29.7 months (T: 54.1 months; TC: 18 months). There was a high rate of febrile neutropenia (7 patients) that occurred despite a reduction in amrubicin dose and one related death. Five patients had reduction in LVEF below 50% during the course of treatment resulting in treatment discontinuation in one patient. Conclusion: Amrubicin shows promise as a single agent in heavily pre-treated patients with thymic malignancies. Notable side effects include febrile neutropenia and the use of growth factor support is essential. Further investigation of this agent is warranted.

Original languageEnglish (US)
Pages (from-to)71-75
Number of pages5
JournalLung Cancer
Volume137
DOIs
StatePublished - Nov 2019

Fingerprint

Thymoma
Neoplasms
Febrile Neutropenia
amrubicin
Topoisomerase II Inhibitors
Therapeutics
Anthracyclines
Disease-Free Survival
Intercellular Signaling Peptides and Proteins
Drug Therapy
Survival
Incidence

Keywords

  • Advanced stage
  • Amrubicin
  • Thymic carcinoma
  • Thymoma

ASJC Scopus subject areas

  • Oncology
  • Pulmonary and Respiratory Medicine
  • Cancer Research

Cite this

Phase II trial of single agent amrubicin in patients with previously treated advanced thymic malignancies. / Hellyer, Jessica A.; Gubens, Matthew A.; Cunanan, Kristen M.; Padda, Sukhmani K.; Burns, Matthew; Spittler, A. John; Riess, Jonathan W.; San Pedro-Salcedo, Melanie; Ramchandran, Kavitha J.; Neal, Joel W.; Wakelee, Heather A.; Loehrer, Patrick J.

In: Lung Cancer, Vol. 137, 11.2019, p. 71-75.

Research output: Contribution to journalArticle

Hellyer, JA, Gubens, MA, Cunanan, KM, Padda, SK, Burns, M, Spittler, AJ, Riess, JW, San Pedro-Salcedo, M, Ramchandran, KJ, Neal, JW, Wakelee, HA & Loehrer, PJ 2019, 'Phase II trial of single agent amrubicin in patients with previously treated advanced thymic malignancies', Lung Cancer, vol. 137, pp. 71-75. https://doi.org/10.1016/j.lungcan.2019.09.015
Hellyer, Jessica A. ; Gubens, Matthew A. ; Cunanan, Kristen M. ; Padda, Sukhmani K. ; Burns, Matthew ; Spittler, A. John ; Riess, Jonathan W. ; San Pedro-Salcedo, Melanie ; Ramchandran, Kavitha J. ; Neal, Joel W. ; Wakelee, Heather A. ; Loehrer, Patrick J. / Phase II trial of single agent amrubicin in patients with previously treated advanced thymic malignancies. In: Lung Cancer. 2019 ; Vol. 137. pp. 71-75.
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abstract = "Objectives: There are limited treatment options for patients with thymic malignancies. Here we present data supporting treatment with single agent amrubicin, a third generation anthracycline and topoisomerase II inhibitor. Materials and methods: This was a phase 2 open-label, single arm trial of amrubicin in patients with thymoma (T) or thymic carcinoma (TC), conducted at two academic institutions. Patients were included if they had received at least one prior chemotherapy regimen. The first 18 patients received amrubicin at 40 mg/m2 IV days 1–3 repeated every 3-weeks. Due to the high incidence of febrile neutropenia, dosing was subsequently amended to 35 mg/m2 for the final 15 patients. Results: A total of 33 patients (14 T/19 TC) were enrolled from 2011 to 2014. Median number of prior therapies was 2. Best response included 6 partial responses, 21 stable disease, and 6 progressive disease (all TC). Objective response rate was 18{\%} (90{\%} exact binomial CI 8.2{\%}–32.8{\%}; T = 4/14 (29{\%}), TC = 2/19 (11{\%})). Median progression-free survival was 7.7 months (T: 8.3 months; TC: 7.3) and median overall survival was 29.7 months (T: 54.1 months; TC: 18 months). There was a high rate of febrile neutropenia (7 patients) that occurred despite a reduction in amrubicin dose and one related death. Five patients had reduction in LVEF below 50{\%} during the course of treatment resulting in treatment discontinuation in one patient. Conclusion: Amrubicin shows promise as a single agent in heavily pre-treated patients with thymic malignancies. Notable side effects include febrile neutropenia and the use of growth factor support is essential. Further investigation of this agent is warranted.",
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AU - Gubens, Matthew A.

AU - Cunanan, Kristen M.

AU - Padda, Sukhmani K.

AU - Burns, Matthew

AU - Spittler, A. John

AU - Riess, Jonathan W.

AU - San Pedro-Salcedo, Melanie

AU - Ramchandran, Kavitha J.

AU - Neal, Joel W.

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N2 - Objectives: There are limited treatment options for patients with thymic malignancies. Here we present data supporting treatment with single agent amrubicin, a third generation anthracycline and topoisomerase II inhibitor. Materials and methods: This was a phase 2 open-label, single arm trial of amrubicin in patients with thymoma (T) or thymic carcinoma (TC), conducted at two academic institutions. Patients were included if they had received at least one prior chemotherapy regimen. The first 18 patients received amrubicin at 40 mg/m2 IV days 1–3 repeated every 3-weeks. Due to the high incidence of febrile neutropenia, dosing was subsequently amended to 35 mg/m2 for the final 15 patients. Results: A total of 33 patients (14 T/19 TC) were enrolled from 2011 to 2014. Median number of prior therapies was 2. Best response included 6 partial responses, 21 stable disease, and 6 progressive disease (all TC). Objective response rate was 18% (90% exact binomial CI 8.2%–32.8%; T = 4/14 (29%), TC = 2/19 (11%)). Median progression-free survival was 7.7 months (T: 8.3 months; TC: 7.3) and median overall survival was 29.7 months (T: 54.1 months; TC: 18 months). There was a high rate of febrile neutropenia (7 patients) that occurred despite a reduction in amrubicin dose and one related death. Five patients had reduction in LVEF below 50% during the course of treatment resulting in treatment discontinuation in one patient. Conclusion: Amrubicin shows promise as a single agent in heavily pre-treated patients with thymic malignancies. Notable side effects include febrile neutropenia and the use of growth factor support is essential. Further investigation of this agent is warranted.

AB - Objectives: There are limited treatment options for patients with thymic malignancies. Here we present data supporting treatment with single agent amrubicin, a third generation anthracycline and topoisomerase II inhibitor. Materials and methods: This was a phase 2 open-label, single arm trial of amrubicin in patients with thymoma (T) or thymic carcinoma (TC), conducted at two academic institutions. Patients were included if they had received at least one prior chemotherapy regimen. The first 18 patients received amrubicin at 40 mg/m2 IV days 1–3 repeated every 3-weeks. Due to the high incidence of febrile neutropenia, dosing was subsequently amended to 35 mg/m2 for the final 15 patients. Results: A total of 33 patients (14 T/19 TC) were enrolled from 2011 to 2014. Median number of prior therapies was 2. Best response included 6 partial responses, 21 stable disease, and 6 progressive disease (all TC). Objective response rate was 18% (90% exact binomial CI 8.2%–32.8%; T = 4/14 (29%), TC = 2/19 (11%)). Median progression-free survival was 7.7 months (T: 8.3 months; TC: 7.3) and median overall survival was 29.7 months (T: 54.1 months; TC: 18 months). There was a high rate of febrile neutropenia (7 patients) that occurred despite a reduction in amrubicin dose and one related death. Five patients had reduction in LVEF below 50% during the course of treatment resulting in treatment discontinuation in one patient. Conclusion: Amrubicin shows promise as a single agent in heavily pre-treated patients with thymic malignancies. Notable side effects include febrile neutropenia and the use of growth factor support is essential. Further investigation of this agent is warranted.

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