Substantial susceptibility of chronic lymphocytic leukemia to BCL2 inhibition: Results of a phase I study of navitoclax in patients with relapsed or refractory disease

Journal of Clinical Oncology

Volumn 30, Issue 5, 2012, Pages 488-496

  Roberts, Andrew W ^a,b,c,d   Seymour, John F ^c,e   Brown, Jennifer R ^f   Wierda, William G ^g   Kipps, Thomas J ^h   Khaw, Seong Lin ^b,d   Carney, Dennis A ^d,e   He, Simon Z ^a,b,d   Huang, David C S ^b,c,d   Xiong, Hao ⁱ   Cui, Yue ⁱ   Busman, Todd A ⁱ   McKeegan, Evelyn M ⁱ   Krivoshik, Andrew P ⁱ   Enschede, Sari H ⁱ   Humerickhouse, Rod ⁱ  

^a ROYAL MELBOURNE HOSPITAL   (Australia)

^b WALTER AND ELIZA HALL INSTITUTE OF MEDICAL RESEARCH   (Australia)

^c Australian Cancer Research Foundation Centre for Therapeutic Target Discovery   (Australia)

^d UNIVERSITY OF MELBOURNE   (Australia)

^e PETER MACCALLUM CANCER CENTRE   (Australia)

^f DANA FARBER CANCER INSTITUTE   (United States)

^g UNIVERSITY OF TEXAS MD ANDERSON CANCER CENTER   (United States)

^h UNIVERSITY OF CALIFORNIA   (United States)

ⁱ ABBOTT LABORATORIES   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

FLUDARABINE; NAVITOCLAX; PROTEIN BCL 2; PROTEIN BCL W; PROTEIN BCL XL; PROTEIN MCL 1;

ABDOMINAL PAIN; ADULT; AGED; ALOPECIA; APOPTOSIS; ARTHRALGIA; ARTICLE; BASAL CELL CARCINOMA; BIOLOGICAL ACTIVITY; CANCER RELAPSE; CANCER SUSCEPTIBILITY; CHRONIC LYMPHATIC LEUKEMIA; CLINICAL ARTICLE; CONTUSION; COUGHING; DECREASED APPETITE; DIARRHEA; DIZZINESS; DOSE RESPONSE; DRUG DOSE ESCALATION; DRUG SAFETY; DRUG WITHDRAWAL; DRY SKIN; DYSPEPSIA; DYSPNEA; EPISTAXIS; FATIGUE; FEMALE; FEVER; HEADACHE; HERPES SIMPLEX; HUMAN; HYPERTENSION; IN VITRO STUDY; INFLUENZA; INSOMNIA; LEUKEMIA CELL; LEUKOPENIA; LOWER RESPIRATORY TRACT INFECTION; LYMPHADENOPATHY; LYMPHOCYTOPENIA; LYMPHOCYTOSIS; MALE; MOUTH PAIN; MULTICENTER STUDY; NAUSEA; NEUTROPENIA; PAIN; PERIPHERAL EDEMA; PHASE 1 CLINICAL TRIAL; PHASE 2 CLINICAL TRIAL; PNEUMONIA; PRIORITY JOURNAL; PROGRESSION FREE SURVIVAL; PROTEIN EXPRESSION; RASH; RHINOPHARYNGITIS; SINUSITIS; SKIN DEFECT; SORE THROAT; SQUAMOUS CELL CARCINOMA; STOMATITIS; THROMBOCYTOPENIA; TREATMENT DURATION; TUMOR LYSIS SYNDROME; UPPER RESPIRATORY TRACT INFECTION; URINARY TRACT INFECTION; VIRUS INFECTION; VOMITING;

ADMINISTRATION, ORAL; AGED; ANILINE COMPOUNDS; ANTINEOPLASTIC AGENTS; APOPTOSIS REGULATORY PROTEINS; CHROMOSOME DELETION; DRUG ADMINISTRATION SCHEDULE; FEMALE; GENE EXPRESSION REGULATION, NEOPLASTIC; HUMANS; IN SITU HYBRIDIZATION, FLUORESCENCE; LEUKEMIA, LYMPHOCYTIC, CHRONIC, B-CELL; MALE; MEMBRANE PROTEINS; MIDDLE AGED; PROTO-ONCOGENE PROTEINS; PROTO-ONCOGENE PROTEINS C-BCL-2; SULFONAMIDES; THROMBOCYTOPENIA; TREATMENT OUTCOME; TUMOR MARKERS, BIOLOGICAL;

EID: 84863116430     PISSN: 0732183X     EISSN: 15277755     Source Type: Journal    
DOI: 10.1200/JCO.2011.34.7898     Document Type: Article

References (34)

1. O'Brien SM, Claxton DF, Crump M, et al: Phase I study of obatoclax mesylate (GX15-070), a small molecule pan-Bcl-2 family antagonist, in patients with advanced chronic lymphocytic leukemia. Blood 113:299-305, 2009
2. O'Brien SM, Cunningham CC, Golenkov AK, et al: Phase I to II multicenter study of oblimersen sodium, a Bcl-2 antisense oligonucleotide, in patients with advanced chronic lymphocytic leukemia. J Clin Oncol 23:7697-7702, 2005 (Pubitemid 46291834)
3. Oltersdorf T, Elmore SW, Shoemaker AR, et al: An inhibitor of Bcl-2 family proteins induces regression of solid tumours. Nature 435:677-681, 2005 (Pubitemid 40825512)
4. van Delft MF, Wei AH, Mason KD, et al: The BH3 mimetic ABT-737 targets selective Bcl-2 proteins and efficiently induces apoptosis via Bak/Bax if Mcl-1 is neutralized. Cancer Cell 10:389-399, 2006 (Pubitemid 44711953)
5. Tse C, Shoemaker AR, Adickes J, et al: ABT- 263: A potent and orally bioavailable Bcl-2 family inhibitor. Cancer Res 68:3421-3428, 2008
6. Vaux DL, Cory S, Adams JM: Bcl-2 gene promotes haemopoietic cell survival and cooperates with c-myc to immortalize pre-B cells. Nature 335: 440-442, 1988
7. Strasser A, Huang DC, Vaux DL: The role of the bcl-2/ced-9 gene family in cancer and general implications of defects in cell death control for tumourigenesis and resistance to chemotherapy. Biochim Biophys Acta 1333:F151-F178, 1997 (Pubitemid 27509075)
8. Schmitt CA, Lowe SW: Bcl-2 mediates chemoresistance in matched pairs of primary E(mu)- myc lymphomas in vivo. Blood Cells Mol Dis 27:206-216, 2001 (Pubitemid 32299776)
9. Kitada S, Takayama S, De Riel K, et al: Reversal of chemoresistance of lymphoma cells by antisense-mediated reduction of bcl-2 gene expression. Antisense Res Dev 4:71-79, 1994 (Pubitemid 24308374)
10. Miyashita T, Reed JC: bcl-2 gene transfer increases relative resistance of S49.1 and WEHI7.2 lymphoid cells to cell death and DNA fragmentation induced by glucocorticoids and multiple chemotherapeutic drugs. Cancer Res 52:5407-5411, 1992
11. Deng J, Carlson N, Takeyama K, et al: BH3 profiling identifies three distinct classes of apoptotic blocks to predict response to ABT-737 and conventional chemotherapeutic agents. Cancer Cell 12:171-185, 2007 (Pubitemid 47199122)
12. Tahir SK, Yang X, Anderson MG, et al: Influence of Bcl-2 family members on the cellular response of small-cell lung cancer cell lines to ABT-737. Cancer Res 67:1176-1183, 2007
13. Tahir SK, Wass J, Joseph MK, et al: Identification of expression signatures predictive of sensitivity to the Bcl-2 family member inhibitor ABT-263 in small cell lung carcinoma and leukemia/lymphoma cell lines. Mol Cancer Ther 9:545-557, 2010
14. Mason KD, Vandenberg CJ, Scott CL, et al: In vivo efficacy of the Bcl-2 antagonist ABT-737 against aggressive Myc-driven lymphomas. Proc Natl Acad Sci U S A 105:17961-17966, 2008
15. Ackler S, Mitten MJ, Foster K, et al: The Bcl-2 inhibitor ABT-263 enhances the response of multiple chemotherapeutic regimens in hematologic tumors in vivo. Cancer Chemother Pharmacol 66:869-880, 2010
16. Del Gaizo Moore V, Brown JR, Certo M, et al: Chronic lymphocytic leukemia requires BCL2 to sequester prodeath BIM, explaining sensitivity to BCL2 antagonist ABT-737. J Clin Invest 117:112- 121, 2007
17. Vogler M, Dinsdale D, Sun XM, et al: A novel paradigm for rapid ABT-737-induced apoptosis involving outer mitochondrial membrane rupture in primary leukemia and lymphoma cells. Cell Death Differ 15:820-830, 2008 (Pubitemid 351524424)
18. Vogler M, Furdas SD, Jung M, et al: Diminished sensitivity of chronic lymphocytic leukemia cells to ABT-737 and ABT-263 due to albumin binding in blood. Clin Cancer Res 16:4217-4225, 2010
19. Mason KD, Khaw SL, Rayeroux KC, et al: The BH3 mimetic compound, ABT-737, synergizes with a range of cytotoxic chemotherapy agents in chronic lymphocytic leukemia. Leukemia 23:2034-2041, 2009
20. Mason KD, Carpinelli MR, Fletcher JI, et al: Programmed anuclear cell death delimits platelet life span. Cell 128:1173-1186, 2007 (Pubitemid 46427871)
21. Nakayama K, Nakayama K, Negishi I, et al: Targeted disruption of Bcl-2 alpha beta in mice: Occurrence of gray hair, polycystic kidney disease, and lymphocytopenia. Proc Natl Acad Sci U S A 91:3700-3704, 1994
22. Print CG, Loveland KL, Gibson L, et al: Apoptosis regulator bcl-w is essential for spermatogenesis but appears otherwise redundant. Proc Natl Acad Sci U S A 95:12424-12431, 1998 (Pubitemid 28483781)
23. Zhang H, Nimmer PM, Tahir SK, et al: Bcl-2 family proteins are essential for platelet survival. Cell Death Differ 14:943-951, 2007 (Pubitemid 46655455)
24. Schoenwaelder SM, Yuan Y, Josefsson EC, et al: Two distinct pathways regulate platelet phosphatidylserine exposure and procoagulant function. Blood 114:663-666, 2009
25. Storer BE: An evaluation of phase I clinical trial designs in the continuous dose-response setting. Stat Med 20:2399-2408, 2001
26. Potter DM: Adaptive dose finding for phase I clinical trials of drugs used for chemotherapy of cancer. Stat Med 21:1805-1823, 2002
27. Cancer Therapy Evaluation Program: Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0. http://ctep.cancer.gov/protocolDevelopment/ electronic-applications/ctc.htm
28. Cheson BD, Bennett JM, Grever M, et al: National Cancer Institute-sponsored Working Group guidelines for chronic lymphocytic leukemia: Revised guidelines for diagnosis and treatment. Blood 87:4990-4997, 1996 (Pubitemid 26189840)
29. Hallek M, Cheson BD, Catovsky D, et al: Guidelines for the diagnosis and treatment of chronic lymphocytic leukemia: A report from the International Workshop on Chronic Lymphocytic Leukemia updating the National Cancer Institute- Working Group 1996 guidelines. Blood 111:5446-5456, 2008
30. Döhner H, Stilgenbauer S, Benner A, et al: Genomic aberrations and survival in chronic lymphocytic leukemia. N Engl J Med 343:1910-1916, 2000 (Pubitemid 32064784)
31. Chen L, Willis SN, Wei A, et al: Differential targeting of prosurvival Bcl-2 proteins by their BH3- only ligands allows complementary apoptotic function. Mol Cell 17:393-403, 2005 (Pubitemid 40193310)
32. Wilson WH, O'Connor OA, Czuczman MS, et al: Navitoclax, a targeted high-affinity inhibitor of BCL-2, in lymphoid malignancies: A phase 1 dose-escalation study of safety, pharmacokinetics, pharmacodynamics, and antitumour activity. Lancet Oncol 11:1149-1159, 2010
33. Vogler M, Weber K, Dinsdale D, et al: Different forms of cell death induced by putative BCL2 inhibitors. Cell Death Differ 16:1030-1039, 2009
34. Konopleva M, Contractor R, Tsao T, et al: Mechanisms of apoptosis sensitivity and resistance to the BH3 mimetic ABT-737 in acute myeloid leukemia. Cancer Cell 10:375-388, 2006 (Pubitemid 44693472)