Phase II trial of romidepsin (NSC-630176) in previously treated colorectal cancer patients with advanced disease: A Southwest Oncology Group study (S0336)

Robert P. Whitehead, Cathryn Rankin, Paulo M G Hoff, Philip J. Gold, Kevin Billingsley, Robert A. Chapman, Lucas Wong, John H. Ward, James L. Abbruzzese, Charles Blanke

    Research output: Contribution to journalArticle

    49 Citations (Scopus)

    Abstract

    Introduction: Patients with metastatic colorectal cancer who progress on standard chemotherapy have limited treatment options. New and effective drugs are needed for these patients. Romidepsin is a histone deacetylase inhibitor that can alter chromatin structure and gene transcription leading to multiple changes in cellular protein production. This may result in cell cycle arrest and tumor growth inhibition. Romidepsin has shown anti-proliferative activity in vitro against multiple mouse and human tumor cell lines and in vivo in human tumor xenograft models. Patients and methods: Patients were required to have pathologically verified, measurable, metastatic or locally advanced colorectal cancer that was surgically unresectable. They must have failed either one or two prior chemotherapy regimens, had performance status of 0-1, adequate bone marrow, renal and hepatic function, and no significant cardiac disease. Patients were treated with romidepsin at a dose of 13 mg/m2 as a 4-h iv infusion on days 1, 8, and 15 of a 28-day cycle. The study had a two stage design. The primary objective of the study was to determine the confirmed response probability in this group of patients treated with romidepsin. Results: Twenty-eight patients were registered to the study, two of whom were ineligible. One eligible patient refused all treatment and was not analyzed. For the 25 remaining patients, performance status was 0 in 16 patients and 1 in nine patients. Ten patients had received one prior chemotherapy regimen and fifteen 2 prior regimens. Out of the 25 eligible and analyzable patients accrued in the first stage of the protocol, no objective responses were observed and the study was permanently closed. Four patients had stable disease as the best response. Twenty-five patients were assessed for toxicity. No grade 4 or greater toxicities were seen. Fourteen of the 25 patients experienced grade 3 toxicities the most common of which were fatigue or anorexia. Conclusion: Romidepsin at this dose and schedule is ineffective in the treatment of patients with metastatic colorectal cancer after prior chemotherapy. Future trials might evaluate combinations of romidepsin with chemotherapeutic or other agents.

    Original languageEnglish (US)
    Pages (from-to)469-475
    Number of pages7
    JournalInvestigational New Drugs
    Volume27
    Issue number5
    DOIs
    StatePublished - Oct 2009

    Fingerprint

    Colorectal Neoplasms
    Drug Therapy
    romidepsin
    Histone Deacetylase Inhibitors
    Anorexia
    Cell Cycle Checkpoints
    Tumor Cell Line
    Heterografts
    Chromatin
    Fatigue
    Heart Diseases
    Neoplasms
    Appointments and Schedules
    Therapeutics
    Bone Marrow

    Keywords

    • Colorectal cancer
    • Phase II trial
    • Previously treated
    • Romidepsin
    • Southwest Oncology Group

    ASJC Scopus subject areas

    • Pharmacology
    • Pharmacology (medical)
    • Oncology

    Cite this

    Phase II trial of romidepsin (NSC-630176) in previously treated colorectal cancer patients with advanced disease : A Southwest Oncology Group study (S0336). / Whitehead, Robert P.; Rankin, Cathryn; Hoff, Paulo M G; Gold, Philip J.; Billingsley, Kevin; Chapman, Robert A.; Wong, Lucas; Ward, John H.; Abbruzzese, James L.; Blanke, Charles.

    In: Investigational New Drugs, Vol. 27, No. 5, 10.2009, p. 469-475.

    Research output: Contribution to journalArticle

    Whitehead, Robert P. ; Rankin, Cathryn ; Hoff, Paulo M G ; Gold, Philip J. ; Billingsley, Kevin ; Chapman, Robert A. ; Wong, Lucas ; Ward, John H. ; Abbruzzese, James L. ; Blanke, Charles. / Phase II trial of romidepsin (NSC-630176) in previously treated colorectal cancer patients with advanced disease : A Southwest Oncology Group study (S0336). In: Investigational New Drugs. 2009 ; Vol. 27, No. 5. pp. 469-475.
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    abstract = "Introduction: Patients with metastatic colorectal cancer who progress on standard chemotherapy have limited treatment options. New and effective drugs are needed for these patients. Romidepsin is a histone deacetylase inhibitor that can alter chromatin structure and gene transcription leading to multiple changes in cellular protein production. This may result in cell cycle arrest and tumor growth inhibition. Romidepsin has shown anti-proliferative activity in vitro against multiple mouse and human tumor cell lines and in vivo in human tumor xenograft models. Patients and methods: Patients were required to have pathologically verified, measurable, metastatic or locally advanced colorectal cancer that was surgically unresectable. They must have failed either one or two prior chemotherapy regimens, had performance status of 0-1, adequate bone marrow, renal and hepatic function, and no significant cardiac disease. Patients were treated with romidepsin at a dose of 13 mg/m2 as a 4-h iv infusion on days 1, 8, and 15 of a 28-day cycle. The study had a two stage design. The primary objective of the study was to determine the confirmed response probability in this group of patients treated with romidepsin. Results: Twenty-eight patients were registered to the study, two of whom were ineligible. One eligible patient refused all treatment and was not analyzed. For the 25 remaining patients, performance status was 0 in 16 patients and 1 in nine patients. Ten patients had received one prior chemotherapy regimen and fifteen 2 prior regimens. Out of the 25 eligible and analyzable patients accrued in the first stage of the protocol, no objective responses were observed and the study was permanently closed. Four patients had stable disease as the best response. Twenty-five patients were assessed for toxicity. No grade 4 or greater toxicities were seen. Fourteen of the 25 patients experienced grade 3 toxicities the most common of which were fatigue or anorexia. Conclusion: Romidepsin at this dose and schedule is ineffective in the treatment of patients with metastatic colorectal cancer after prior chemotherapy. Future trials might evaluate combinations of romidepsin with chemotherapeutic or other agents.",
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    T1 - Phase II trial of romidepsin (NSC-630176) in previously treated colorectal cancer patients with advanced disease

    T2 - A Southwest Oncology Group study (S0336)

    AU - Whitehead, Robert P.

    AU - Rankin, Cathryn

    AU - Hoff, Paulo M G

    AU - Gold, Philip J.

    AU - Billingsley, Kevin

    AU - Chapman, Robert A.

    AU - Wong, Lucas

    AU - Ward, John H.

    AU - Abbruzzese, James L.

    AU - Blanke, Charles

    PY - 2009/10

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    N2 - Introduction: Patients with metastatic colorectal cancer who progress on standard chemotherapy have limited treatment options. New and effective drugs are needed for these patients. Romidepsin is a histone deacetylase inhibitor that can alter chromatin structure and gene transcription leading to multiple changes in cellular protein production. This may result in cell cycle arrest and tumor growth inhibition. Romidepsin has shown anti-proliferative activity in vitro against multiple mouse and human tumor cell lines and in vivo in human tumor xenograft models. Patients and methods: Patients were required to have pathologically verified, measurable, metastatic or locally advanced colorectal cancer that was surgically unresectable. They must have failed either one or two prior chemotherapy regimens, had performance status of 0-1, adequate bone marrow, renal and hepatic function, and no significant cardiac disease. Patients were treated with romidepsin at a dose of 13 mg/m2 as a 4-h iv infusion on days 1, 8, and 15 of a 28-day cycle. The study had a two stage design. The primary objective of the study was to determine the confirmed response probability in this group of patients treated with romidepsin. Results: Twenty-eight patients were registered to the study, two of whom were ineligible. One eligible patient refused all treatment and was not analyzed. For the 25 remaining patients, performance status was 0 in 16 patients and 1 in nine patients. Ten patients had received one prior chemotherapy regimen and fifteen 2 prior regimens. Out of the 25 eligible and analyzable patients accrued in the first stage of the protocol, no objective responses were observed and the study was permanently closed. Four patients had stable disease as the best response. Twenty-five patients were assessed for toxicity. No grade 4 or greater toxicities were seen. Fourteen of the 25 patients experienced grade 3 toxicities the most common of which were fatigue or anorexia. Conclusion: Romidepsin at this dose and schedule is ineffective in the treatment of patients with metastatic colorectal cancer after prior chemotherapy. Future trials might evaluate combinations of romidepsin with chemotherapeutic or other agents.

    AB - Introduction: Patients with metastatic colorectal cancer who progress on standard chemotherapy have limited treatment options. New and effective drugs are needed for these patients. Romidepsin is a histone deacetylase inhibitor that can alter chromatin structure and gene transcription leading to multiple changes in cellular protein production. This may result in cell cycle arrest and tumor growth inhibition. Romidepsin has shown anti-proliferative activity in vitro against multiple mouse and human tumor cell lines and in vivo in human tumor xenograft models. Patients and methods: Patients were required to have pathologically verified, measurable, metastatic or locally advanced colorectal cancer that was surgically unresectable. They must have failed either one or two prior chemotherapy regimens, had performance status of 0-1, adequate bone marrow, renal and hepatic function, and no significant cardiac disease. Patients were treated with romidepsin at a dose of 13 mg/m2 as a 4-h iv infusion on days 1, 8, and 15 of a 28-day cycle. The study had a two stage design. The primary objective of the study was to determine the confirmed response probability in this group of patients treated with romidepsin. Results: Twenty-eight patients were registered to the study, two of whom were ineligible. One eligible patient refused all treatment and was not analyzed. For the 25 remaining patients, performance status was 0 in 16 patients and 1 in nine patients. Ten patients had received one prior chemotherapy regimen and fifteen 2 prior regimens. Out of the 25 eligible and analyzable patients accrued in the first stage of the protocol, no objective responses were observed and the study was permanently closed. Four patients had stable disease as the best response. Twenty-five patients were assessed for toxicity. No grade 4 or greater toxicities were seen. Fourteen of the 25 patients experienced grade 3 toxicities the most common of which were fatigue or anorexia. Conclusion: Romidepsin at this dose and schedule is ineffective in the treatment of patients with metastatic colorectal cancer after prior chemotherapy. Future trials might evaluate combinations of romidepsin with chemotherapeutic or other agents.

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    KW - Previously treated

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