Clinical and molecular responses in lung cancer patients receiving romidepsin.

Clinical and molecular responses in lung cancer patients receiving romidepsin. Research Abstract Details 

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Clinical and molecular responses in lung cancer patients receiving romidepsin. Abstract Text:

David S Schrump,Maria R Fischette,Dao M Nguyen,Ming Zhao,Xinmin Li,Tricia F Kunst,Ana Hancox,Julie A Hong,G Aaron Chen,Evgeny Kruchin,John J Wright,Douglas R Rosing,Alex Sparreboom,William D Figg,Seth M Steinberg,David S Schrump,Maria R Fischette,Dao M Nguyen,Ming Zhao,Xinmin Li,Tricia F Kunst,Ana Hancox,Julie A Hong,G Aaron Chen,Evgeny Kruchin,John J Wright,Douglas R Rosing,Alex Sparreboom,William D Figg,Seth M Steinberg,David S Schrump,Maria R Fischette,Dao M Nguyen,Ming Zhao,Xinmin Li,Tricia F Kunst,Ana Hancox,Julie A Hong,G Aaron Chen,Evgeny Kruchin,John J Wright,Douglas R Rosing,Alex Sparreboom,William D Figg,Seth M Steinberg,

PURPOSE: Our preclinical experiments indicated that Romidepsin (Depsipeptide FK228; DP) mediates growth arrest and apoptosis in cultured lung cancer cells. A phase II trial was done to examine clinical and molecular responses mediated by this histone deacetylase inhibitor in lung cancer patients. EXPERIMENTAL DESIGN: Nineteen patients with neoplasms refractory to standard therapy received 4-h DP infusions (17.8 mg/m(2)) on days 1 and 7 of a 21-day cycle. Each full course of therapy consisted of two identical 21-day cycles. Plasma DP levels were evaluated by liquid chromatography-mass spectrometry techniques. A variety of molecular end points were assessed in tumor biopsies via immunohistochemistry techniques. Long oligo arrays were used to examine gene expression profiles in laser-captured tumor cells before and after DP exposure, relative to lung cancer cells and adjacent normal bronchial epithelia from patients undergoing pulmonary resections. RESULTS: Nineteen patients were evaluable for toxicity assessment; 18 were evaluable for treatment response. Myelosuppression was dose limiting in one individual. No significant cardiac toxicities were observed. Maximum steady-state plasma DP concentrations ranged from 384 to 1,114 ng/mL. No objective responses were observed. Transient stabilization of disease was noted in nine patients. DP enhanced acetylation of histone H4, increased p21 expression in lung cancer cells, and seemed to shift global gene expression profiles in these cells toward those detected in normal bronchial epithelia. CONCLUSION: Although exhibiting minimal clinical efficacy at this dose and schedule, DP mediates biological effects that may warrant further evaluation of this histone deacetylase inhibitor in combination with novel-targeted agents in lung cancer patients.

Clinical and molecular responses in lung cancer patients receiving romidepsin. Publishing Authors By Initials

DS Schrump,MR Fischette,DM Nguyen,M Zhao,X Li,TF Kunst,A Hancox,JA Hong,GA Chen,E Kruchin,JJ Wright,DR Rosing,A Sparreboom,WD Figg,SM Steinberg,DS Schrump,MR Fischette,DM Nguyen,M Zhao,X Li,TF Kunst,A Hancox,JA Hong,GA Chen,E Kruchin,JJ Wright,DR Rosing,A Sparreboom,WD Figg,SM Steinberg,DS Schrump,MR Fischette,DM Nguyen,M Zhao,X Li,TF Kunst,A Hancox,JA Hong,GA Chen,E Kruchin,JJ Wright,DR Rosing,A Sparreboom,WD Figg,SM Steinberg,

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Clinical and molecular responses in lung cancer patients receiving romidepsin. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: Clinical cancer research : an official journal of

VOLUME: 14

Page Numbers: 188-98

Journal Abbreviation: Clin. Cancer Res.

ISSN: 1078-0432

DAY: 1

MONTH: Jan

YEAR: 2008

Clinical and molecular responses in lung cancer patients receiving romidepsin. Information

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LANGUAGE: eng

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AFFILIATION: Authors' Affiliations:Thoracic Oncology Section Surgery Branch, Medical Oncology Branch, Biostatistics and Data Management Section, Center for Cancer Research and Cancer Therapy Evaluation Program, National Cancer Institute.

Country: United States

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MEDLINETA: Clin Cancer Res

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