Substantial Susceptibility of Chronic Lymphocytic Leukemia to BCL2 Inhibition: Results of a Phase I Study of Navitoclax in Patients With Relapsed or Refractory Disease

• Published in: Journal of clinical oncology Vol. 30; no. 5; pp. 488 - 496
• Main Authors: Roberts, Andrew W., Seymour, John F., Brown, Jennifer R., Wierda, William G., Kipps, Thomas J., Khaw, Seong Lin, Carney, Dennis A., He, Simon Z., Huang, David C.S., Xiong, Hao, Cui, Yue, Busman, Todd A., McKeegan, Evelyn M., Krivoshik, Andrew P., Enschede, Sari H., Humerickhouse, Rod
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Society of Clinical Oncology 10.02.2012
• Subjects: Administration, Oral; Aged; Aniline Compounds - administration & dosage; Aniline Compounds - adverse effects; Aniline Compounds - pharmacokinetics; Aniline Compounds - pharmacology; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - adverse effects; Antineoplastic Agents - pharmacokinetics; Antineoplastic Agents - pharmacology; Apoptosis Regulatory Proteins - metabolism; Bcl-2-Like Protein 11; Biological and medical sciences; Biomarkers, Tumor - metabolism; Chromosome Deletion; Drug Administration Schedule; Female; Gene Expression Regulation, Neoplastic; Hematologic and hematopoietic diseases; Humans; In Situ Hybridization, Fluorescence; Leukemia, Lymphocytic, Chronic, B-Cell - drug therapy; Leukemia, Lymphocytic, Chronic, B-Cell - genetics; Leukemia, Lymphocytic, Chronic, B-Cell - metabolism; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Male; Medical sciences; Membrane Proteins - metabolism; Middle Aged; Myeloid Cell Leukemia Sequence 1 Protein; ORIGINAL REPORTS; Proto-Oncogene Proteins - metabolism; Proto-Oncogene Proteins c-bcl-2 - antagonists & inhibitors; Proto-Oncogene Proteins c-bcl-2 - metabolism; Sulfonamides - administration & dosage; Sulfonamides - adverse effects; Sulfonamides - pharmacokinetics; Sulfonamides - pharmacology; Thrombocytopenia - chemically induced; Treatment Outcome; Tumors; Human; Relapse; Treatment resistance; Malignant hemopathy; Chronic lymphocytic leukemia; Cancerology; Treatment; Lymphoproliferative syndrome; C-Onc gene; Phase I trial; Inhibitor; Protooncogene; Cancer

BCL2 overexpression is a hallmark of chronic lymphocytic leukemia (CLL). The novel BH3 mimetic navitoclax (ABT-263) specifically inhibits BCL2 and related proteins BCL-x(l) and BCL-w, potently inducing apoptosis of CLL cells in vitro. A phase I trial in patients with CLL was conducted to evaluate th...