SARC018-SPORE02

Phase II Study of Mocetinostat Administered with Gemcitabine for Patients with Metastatic Leiomyosarcoma with Progression or Relapse following Prior Treatment with Gemcitabine-Containing Therapy

Edwin Choy, Karla Ballman, James Chen, Mark A. Dickson, Rashmi Chugh, Suzanne George, Scott Heitaka Okuno, Raphael Pollock, Rajiv M. Patel, Antje Hoering, Shreyaskumar Patel

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Histone deacetylase inhibitors (HDACi) can reverse chemoresistance, enhance chemotherapy-induced cytotoxicity, and reduce sarcoma proliferation in cell lines and animal models. We sought to determine the safety and toxicity of mocetinostat and its ability to reverse chemoresistance when administered with gemcitabine in patients with metastatic leiomyosarcoma resistant to prior gemcitabine-containing therapy. Participants with metastatic leiomyosarcoma received mocetinostat orally, 70 mg per day, three days per week, increasing to 90 mg after three weeks if well tolerated. Gemcitabine was administered at 1,000 mg/m2 intravenously at 10 mg/m2/minute on days five and 12 of every 21-day cycle. Disease response was evaluated with CT or MRI. Twenty participants with leiomyosarcoma were evaluated for toxicity. Median time to disease progression was 2.0 months (95% CI 1.54-3.12). Eighteen participants were evaluated for radiologic response by RECIST 1.1. Best responses included one PR and 12 SD. Tumor size reduced in 3 patients. Most common toxicities were fatigue, thrombocytopenia, anemia, nausea, and anorexia. One patient experienced a significant pericardial adverse event. No study-related deaths were observed. Rechallenging with gemcitabine by adding mocetinostat was feasible and demonstrated modest activity in patients with leiomyosarcoma. Further studies are needed to better define the role of HDAC inhibitors in patients with metastatic leiomyosarcoma.

Original languageEnglish (US)
Article number2068517
JournalSarcoma
Volume2018
DOIs
StatePublished - Jan 1 2018

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gemcitabine
Leiomyosarcoma
Recurrence
Histone Deacetylase Inhibitors
Therapeutics
Anorexia
Sarcoma
Thrombocytopenia
Nausea
Fatigue
Disease Progression
Anemia
Animal Models
mocetinostat
Safety
Drug Therapy
Cell Line

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging

Cite this

SARC018-SPORE02 : Phase II Study of Mocetinostat Administered with Gemcitabine for Patients with Metastatic Leiomyosarcoma with Progression or Relapse following Prior Treatment with Gemcitabine-Containing Therapy. / Choy, Edwin; Ballman, Karla; Chen, James; Dickson, Mark A.; Chugh, Rashmi; George, Suzanne; Okuno, Scott Heitaka; Pollock, Raphael; Patel, Rajiv M.; Hoering, Antje; Patel, Shreyaskumar.

In: Sarcoma, Vol. 2018, 2068517, 01.01.2018.

Research output: Contribution to journalArticle

Choy, Edwin ; Ballman, Karla ; Chen, James ; Dickson, Mark A. ; Chugh, Rashmi ; George, Suzanne ; Okuno, Scott Heitaka ; Pollock, Raphael ; Patel, Rajiv M. ; Hoering, Antje ; Patel, Shreyaskumar. / SARC018-SPORE02 : Phase II Study of Mocetinostat Administered with Gemcitabine for Patients with Metastatic Leiomyosarcoma with Progression or Relapse following Prior Treatment with Gemcitabine-Containing Therapy. In: Sarcoma. 2018 ; Vol. 2018.
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abstract = "Histone deacetylase inhibitors (HDACi) can reverse chemoresistance, enhance chemotherapy-induced cytotoxicity, and reduce sarcoma proliferation in cell lines and animal models. We sought to determine the safety and toxicity of mocetinostat and its ability to reverse chemoresistance when administered with gemcitabine in patients with metastatic leiomyosarcoma resistant to prior gemcitabine-containing therapy. Participants with metastatic leiomyosarcoma received mocetinostat orally, 70 mg per day, three days per week, increasing to 90 mg after three weeks if well tolerated. Gemcitabine was administered at 1,000 mg/m2 intravenously at 10 mg/m2/minute on days five and 12 of every 21-day cycle. Disease response was evaluated with CT or MRI. Twenty participants with leiomyosarcoma were evaluated for toxicity. Median time to disease progression was 2.0 months (95{\%} CI 1.54-3.12). Eighteen participants were evaluated for radiologic response by RECIST 1.1. Best responses included one PR and 12 SD. Tumor size reduced in 3 patients. Most common toxicities were fatigue, thrombocytopenia, anemia, nausea, and anorexia. One patient experienced a significant pericardial adverse event. No study-related deaths were observed. Rechallenging with gemcitabine by adding mocetinostat was feasible and demonstrated modest activity in patients with leiomyosarcoma. Further studies are needed to better define the role of HDAC inhibitors in patients with metastatic leiomyosarcoma.",
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