Phase I to II multicenter study of oblimersen sodium, a Bcl-2 antisense oligonucleotide, in patients with advanced chronic lymphocytic leukemia

Journal of Clinical Oncology

Volumn 23, Issue 30, 2005, Pages 7697-7702

  O'Brien, Susan M ^a   Cunningham, Charles C ^a   Golenkov, Anatoliy K ^a   Turkina, Anna G ^a   Novick, Steven C ^a   Rai, Kanti R ^a  

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

Author keywords

[No Author keywords available]

Indexed keywords

ANTISENSE OLIGONUCLEOTIDE; DRUG METABOLITE; FLUDARABINE; OBLIMERSEN; PROTEIN BCL 2; MESSENGER RNA; NUCLEOTIDE;

ADULT; ADVANCED CANCER; AGED; ANOREXIA; ANTINEOPLASTIC ACTIVITY; ANTISENSE THERAPY; ANXIETY; ARTHRALGIA; CANCER FATIGUE; CANCER RELAPSE; CHRONIC LYMPHATIC LEUKEMIA; CLINICAL ARTICLE; CLINICAL TRIAL; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; COUGHING; CYTOKINE RELEASE; DEHYDRATION; DIARRHEA; DOSE RESPONSE; DRUG BLOOD LEVEL; DRUG CLEARANCE; DRUG DOSE REDUCTION; DRUG EFFICACY; DRUG ELIMINATION; DRUG METABOLISM; DRUG RESPONSE; DRUG SAFETY; DRUG WITHDRAWAL; DUODENUM OBSTRUCTION; DYSPNEA; FEMALE; FEVER; HEART ATRIUM FIBRILLATION; HEPATOMEGALY; HUMAN; HYPOKALEMIA; HYPOMAGNESEMIA; HYPOTENSION; INJECTION SITE REACTION; MALE; MAXIMUM TOLERATED DOSE; MULTICENTER STUDY; MULTIPLE CYCLE TREATMENT; NAUSEA; NEUTROPENIA; NIGHT SWEAT; PHASE 1 CLINICAL TRIAL; PHASE 2 CLINICAL TRIAL; PNEUMONIA; PRIORITY JOURNAL; RASH; REVIEW; SIDE EFFECT; SPLENOMEGALY; VOMITING; ARTICLE; DRUG EFFECT; GENE EXPRESSION REGULATION; GENETICS; INTRAVENOUS DRUG ADMINISTRATION; METABOLISM; MIDDLE AGED; PROGNOSIS; REMISSION; SURVIVAL RATE;

ADULT; AGED; DOSE-RESPONSE RELATIONSHIP, DRUG; FEMALE; GENE EXPRESSION REGULATION, LEUKEMIC; HUMANS; INFUSIONS, INTRAVENOUS; LEUKEMIA, LYMPHOCYTIC, CHRONIC; MALE; MAXIMUM TOLERATED DOSE; MIDDLE AGED; OLIGONUCLEOTIDES, ANTISENSE; PROGNOSIS; PROTO-ONCOGENE PROTEINS C-BCL-2; REMISSION INDUCTION; RNA, MESSENGER; SURVIVAL RATE; THIONUCLEOTIDES;

EID: 32944475363     PISSN: 0732183X     EISSN: None     Source Type: Journal    
DOI: 10.1200/JCO.2005.02.4364     Document Type: Review

References (23)

1. Wu GS, El-Deiry WS: Apoptotic death of tumor cells correlates with chemosensitivity, independent of p53 or Bcl-2. Clin Cancer Res 2:623-633, 1996
2. Perry DK, Smyth MJ, Wang H-G, et al: Bcl-2 acts upstream of the PARP protease and prevents its activation. Cell Death Differ 4:29-33, 1997
3. Chen LB: Mitochondrial membrane potential in living cells. Annu Rev Cell Biol 4:155-181, 1988
4. Beham A, Marin MC, Fernandez A, et al: Bcl-2 inhibits p53 nuclear import following DNA damage. Oncogene 15:2767-2772, 1997
5. Tsujimoto Y, Cossman J, Jaffe E, et al: Involvement of the bcl-2 gene in human follicular lymphoma. Science 228:1440-1443, 1985
6. Lazaridou A, Miraxtsi C, Korantzis J, et al: Simultaneous detection of BCL-2 protein, trisomy 12, retinoblastoma and P53 monoallelic gene deletions in B-cell chronic lymphocytic leukemia by fluorescence in situ hybridization (FISH): Relation to disease status. Leuk Lymphoma 36:503-512, 2000
7. Pepper C, Bentley P, Hoy T: Regulation of clinical chemoresistance by bcl-2 and bax oncoproteins in B-cell chronic lymphocytic leukaemia. Br J Haematol 95:513-517, 1996
8. Veis DJ, Sorenson CM, Shutter JR, et al: Bcl-2-deficient mice demonstrate fulminant lymphoid apoptosis, polycystic kidneys, and hypopigmented hair. Cell 75:229-240, 1993
9. Klasa RJ, Gillum AM, Klem RE, et al: Oblimersen Bcl-2 antisense: Facilitating apoptosis in anticancer treatment. Antisense Nucleic Acid Drug Dev 12:193-213, 2002
10. Pepper C, Thomas A, Hoy T, et al: Antisense-mediated suppression of Bcl-2 highlights its pivotal role in failed apoptosis in B-cell chronic lymphocytic leukaemia. Br J Haematol 107:611-615, 1999
11. Joshi SS, Wang P, Dickinson JE, et al: Manipulation of differentially expressed genes such as bcl-2 leads to increased killing of B chronic lymphocytic leukemia. Proc Am Assoc Cancer Res 42:659, 2001 (abstr 3547)
12. Auer RL, Corbo M, Fegan CD, et al: Bcl-2 antisense (Genasense) induces apoptosis and potentiates activity of both cytotoxic chemotherapy and rituximab in primary CLL cells. Blood 98:808a, 2001 (suppl, abstr)
13. Cotter FE, Auer M, Corbo S, et al: Oblimersen sodium (G3139) sensitizes malignant B-cells to alemtuzumab induced apoptosis. J Clin Oncol 22:227a, 2003 (suppl, abstr 910)
14. 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
15. Jansen B, Wacheck V, Heere-Ress E, et al: Clinical, pharmacologic, and pharmacodynamic study of Genasense (G3139, Bcl-2 antisense oligonucleotide) and dacarbazine (DTIC) in patients with malignant melanoma. Proc Am Soc Clin Oncol 20:357a, 2001 (abstr 1426)
16. Winkler U, Jensen M, Manzke O, et al: Cytokine-release syndrome in patients with B-cell chronic lymphocytic leukemia and high lymphocyte counts after treatment with an anti-CD20 monoclonal antibody (rituximab, IDEC-C2B8). Blood 94:2217-2224, 1999
17. Chanan-Khan AA, Mavromatis B, Kanti R, et al: Pilot study of Genasense (oblimersen sodium, Bcl-2 antisense oligonucleotide), fludarabine and rituximab in previously treated and untreated subjects with chronic lymphocytic leukemia. Blood 104:289b, 2004 (suppl)
18. Waters JS, Webb A, Cunningham D, et al: Phase I clinical and pharmacokinetic study of bcl-2 antisense oligonucleotide therapy in patients with non-Hodgkin's lymphoma. J Clin Oncol 18:1812-1823, 2000
19. Raynaud FI, Orr RM, Goddard PM, et al: Pharmacokinetics of G3139, a phosphorothioate oligodeoxynucleotide antisense to Bcl-2, after intravenous administration or continuous subcutaneous infusion to mice. J Pharmacol Exp Ther 281:420-427, 1997
20. Genta Incorporated: Data on file. Berkeley Heights, NJ, Genta Incorporated
21. Cossum PA, Sasmor H, Dellinger D, et al: Disposition of the 14C-labeled phosphorothioate oligonucleotide ISIS 2105 after intravenous administration to rats. J Pharmacol Exp Ther 267: 1181-1190, 1993
22. Cossum PA, Truong L, Owens SR, et al: Pharmacokinetics of a 14C-labeled phosphorothioate oligonucleotide, ISIS 2105, after intradermal administration to rats. J Pharmacol Exp Ther 269:89-94, 1994
23. Crooke ST, Grillone LR, Tendolkar A, et al: A pharmacokinetic evaluation of 14C-labeled afovirsen sodium in patients with genital warts. Clin Pharmacol Ther 56:641-646, 1994