Clinical Experience With Intravenous and Oral Formulations of the Novel Histone Deacetylase Inhibitor Suberoylanilide Hydroxamic Acid in Patients With Advanced Hematologic Malignancies

Owen A O'Connor; Mark L Heaney; Lawrence Schwartz; Stacie Richardson; Robert Willim; Barbara MacGregor-Cortelli; Tracey Curly; Craig Moskowitz; Carol Portlock; Steven Horwitz; Andrew D Zelenetz; Stanley Frankel; Victoria Richon; Paul Marks; William K Kelly

doi:10.1200/JCO.2005.01.9679

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Clinical Experience With Intravenous and Oral Formulations of the Novel Histone Deacetylase Inhibitor Suberoylanilide Hydroxamic Acid in Patients With Advanced Hematologic Malignancies

Journal article

Peer reviewed

Clinical Experience With Intravenous and Oral Formulations of the Novel Histone Deacetylase Inhibitor Suberoylanilide Hydroxamic Acid in Patients With Advanced Hematologic Malignancies

Owen A O'Connor, Mark L Heaney, Lawrence Schwartz, Stacie Richardson, Robert Willim, Barbara MacGregor-Cortelli, Tracey Curly, Craig Moskowitz, Carol Portlock, Steven Horwitz, …

Journal of clinical oncology, Vol.24(1), pp.166-173

2006-01-01

DOI: https://doi.org/10.1200/JCO.2005.01.9679

PMID: 16330674

Abstract

Purpose To document the toxicity and activity of the histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA) in patients with pretreated hematologic malignancies. Patients and Methods Two formulations of SAHA (intravenous [IV] and oral) have been assessed in two consecutive phase I trials. In both trials, dose escalation was performed in parallel and independently in patients with solid tumors and hematologic malignancies. Eligible patients were required to have adequate hepatic and renal function, an absolute neutrophil count ≥ 500/μL and a platelet count more than 25,000/mL. All patients provided informed consent for study inclusion. Results A total of 39 patients with hematologic malignancy were enrolled (14 on IV SAHA and 25 on oral SAHA), of whom 35 were treated. The spectrum of diseases included patients with diffuse large B-cell lymphoma (n = 12), Hodgkin's disease (HD; n = 12), multiple myeloma (n = 2), T-cell lymphoma (n = 3), mantle cell lymphoma (n = 2), small lymphocytic lymphoma (n = 2), and myeloid leukemia (n = 2). Major adverse events with the oral formulation included fatigue, diarrhea, anorexia, and dehydration, whereas myelosuppression and thrombocytopenia were more prominent with the IV formulation. Typically, the hematologic toxicities resolved shortly after SAHA was stopped. There was no neutropenic fever or neutropenic sepsis. Reduction in measurable tumor was observed in five patients. One patient with transformed small lymphocytic lymphoma met criteria for complete response, whereas another met the criteria for partial response (PR). One patient with refractory HD had a PR, whereas three patients had stable disease for up to 9 months. Conclusion These results suggest that SAHA has activity in hematologic malignancies including HD and select subtypes of non-Hodgkin's lymphoma.

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Collaboration types: Industry collaboration; Domestic collaboration
Citation topics: 1 Clinical & Life Sciences; 1.25 Molecular & Cell Biology - Cancer, Autophagy & Apoptosis; 1.25.1461 Histone Deacetylase
Web Of Science research areas: Oncology
ESI research areas: Clinical Medicine

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Title: Clinical Experience With Intravenous and Oral Formulations of the Novel Histone Deacetylase Inhibitor Suberoylanilide Hydroxamic Acid in Patients With Advanced Hematologic Malignancies
Creators: Owen A O'Connor - From the Department of Medicine, Division of Hematologic Oncology, Lymphoma Service, Leukemia Service, Division of Solid Tumor Oncology, Developmental Chemotherapy Service, Genitourinary Oncology Service, Department of Radiology, Department of Nursing, Cell Biology Program, Memorial Sloan-Kettering Cancer Center, Sloan-Kettering Institute, New York, NY; and Merck and Co, Whitehouse Station, NJ
Mark L Heaney - From the Department of Medicine, Division of Hematologic Oncology, Lymphoma Service, Leukemia Service, Division of Solid Tumor Oncology, Developmental Chemotherapy Service, Genitourinary Oncology Service, Department of Radiology, Department of Nursing, Cell Biology Program, Memorial Sloan-Kettering Cancer Center, Sloan-Kettering Institute, New York, NY; and Merck and Co, Whitehouse Station, NJ
Lawrence Schwartz - From the Department of Medicine, Division of Hematologic Oncology, Lymphoma Service, Leukemia Service, Division of Solid Tumor Oncology, Developmental Chemotherapy Service, Genitourinary Oncology Service, Department of Radiology, Department of Nursing, Cell Biology Program, Memorial Sloan-Kettering Cancer Center, Sloan-Kettering Institute, New York, NY; and Merck and Co, Whitehouse Station, NJ
Stacie Richardson - From the Department of Medicine, Division of Hematologic Oncology, Lymphoma Service, Leukemia Service, Division of Solid Tumor Oncology, Developmental Chemotherapy Service, Genitourinary Oncology Service, Department of Radiology, Department of Nursing, Cell Biology Program, Memorial Sloan-Kettering Cancer Center, Sloan-Kettering Institute, New York, NY; and Merck and Co, Whitehouse Station, NJ
Robert Willim - From the Department of Medicine, Division of Hematologic Oncology, Lymphoma Service, Leukemia Service, Division of Solid Tumor Oncology, Developmental Chemotherapy Service, Genitourinary Oncology Service, Department of Radiology, Department of Nursing, Cell Biology Program, Memorial Sloan-Kettering Cancer Center, Sloan-Kettering Institute, New York, NY; and Merck and Co, Whitehouse Station, NJ
Barbara MacGregor-Cortelli - From the Department of Medicine, Division of Hematologic Oncology, Lymphoma Service, Leukemia Service, Division of Solid Tumor Oncology, Developmental Chemotherapy Service, Genitourinary Oncology Service, Department of Radiology, Department of Nursing, Cell Biology Program, Memorial Sloan-Kettering Cancer Center, Sloan-Kettering Institute, New York, NY; and Merck and Co, Whitehouse Station, NJ
Tracey Curly - From the Department of Medicine, Division of Hematologic Oncology, Lymphoma Service, Leukemia Service, Division of Solid Tumor Oncology, Developmental Chemotherapy Service, Genitourinary Oncology Service, Department of Radiology, Department of Nursing, Cell Biology Program, Memorial Sloan-Kettering Cancer Center, Sloan-Kettering Institute, New York, NY; and Merck and Co, Whitehouse Station, NJ
Craig Moskowitz - From the Department of Medicine, Division of Hematologic Oncology, Lymphoma Service, Leukemia Service, Division of Solid Tumor Oncology, Developmental Chemotherapy Service, Genitourinary Oncology Service, Department of Radiology, Department of Nursing, Cell Biology Program, Memorial Sloan-Kettering Cancer Center, Sloan-Kettering Institute, New York, NY; and Merck and Co, Whitehouse Station, NJ
Carol Portlock - From the Department of Medicine, Division of Hematologic Oncology, Lymphoma Service, Leukemia Service, Division of Solid Tumor Oncology, Developmental Chemotherapy Service, Genitourinary Oncology Service, Department of Radiology, Department of Nursing, Cell Biology Program, Memorial Sloan-Kettering Cancer Center, Sloan-Kettering Institute, New York, NY; and Merck and Co, Whitehouse Station, NJ
Steven Horwitz - From the Department of Medicine, Division of Hematologic Oncology, Lymphoma Service, Leukemia Service, Division of Solid Tumor Oncology, Developmental Chemotherapy Service, Genitourinary Oncology Service, Department of Radiology, Department of Nursing, Cell Biology Program, Memorial Sloan-Kettering Cancer Center, Sloan-Kettering Institute, New York, NY; and Merck and Co, Whitehouse Station, NJ
Andrew D Zelenetz - From the Department of Medicine, Division of Hematologic Oncology, Lymphoma Service, Leukemia Service, Division of Solid Tumor Oncology, Developmental Chemotherapy Service, Genitourinary Oncology Service, Department of Radiology, Department of Nursing, Cell Biology Program, Memorial Sloan-Kettering Cancer Center, Sloan-Kettering Institute, New York, NY; and Merck and Co, Whitehouse Station, NJ
Stanley Frankel - From the Department of Medicine, Division of Hematologic Oncology, Lymphoma Service, Leukemia Service, Division of Solid Tumor Oncology, Developmental Chemotherapy Service, Genitourinary Oncology Service, Department of Radiology, Department of Nursing, Cell Biology Program, Memorial Sloan-Kettering Cancer Center, Sloan-Kettering Institute, New York, NY; and Merck and Co, Whitehouse Station, NJ
Victoria Richon - From the Department of Medicine, Division of Hematologic Oncology, Lymphoma Service, Leukemia Service, Division of Solid Tumor Oncology, Developmental Chemotherapy Service, Genitourinary Oncology Service, Department of Radiology, Department of Nursing, Cell Biology Program, Memorial Sloan-Kettering Cancer Center, Sloan-Kettering Institute, New York, NY; and Merck and Co, Whitehouse Station, NJ
Paul Marks - From the Department of Medicine, Division of Hematologic Oncology, Lymphoma Service, Leukemia Service, Division of Solid Tumor Oncology, Developmental Chemotherapy Service, Genitourinary Oncology Service, Department of Radiology, Department of Nursing, Cell Biology Program, Memorial Sloan-Kettering Cancer Center, Sloan-Kettering Institute, New York, NY; and Merck and Co, Whitehouse Station, NJ
William K Kelly - From the Department of Medicine, Division of Hematologic Oncology, Lymphoma Service, Leukemia Service, Division of Solid Tumor Oncology, Developmental Chemotherapy Service, Genitourinary Oncology Service, Department of Radiology, Department of Nursing, Cell Biology Program, Memorial Sloan-Kettering Cancer Center, Sloan-Kettering Institute, New York, NY; and Merck and Co, Whitehouse Station, NJ
Publication Details: Journal of clinical oncology, Vol.24(1), pp.166-173
Academic Unit: Miller School of Medicine; UMMG Department of Medicine
Language: English
Resource Type: Journal article
PMID: 16330674
Record Identifier: 991031614560302976