Obatoclax mesylate, a pan-Bcl-2 inhibitor, in combination with docetaxel in a phase 1/2 trial in relapsed non-small-cell lung cancer

Journal of Thoracic Oncology

Volumn 9, Issue 1, 2014, Pages 121-125

  Chiappori, Alberto ^a   Williams, Charles ^b   Northfelt, Donald W ^c   Adams, John W ^b   Malik, Shakun ^d   Edelman, Martin J ^e   Rosen, Peter ^f   Van Echo, David A ^g   Berger, Mark S ^h   Haura, Eric B ^a  

^a H LEE MOFFITT CANCER CENTER AND RESEARCH INSTITUTE   (United States)

^b Arlington Cancer Center   (United States)

^c MAYO CLINIC   (United States)

^d GEORGETOWN UNIVERSITY HOSPITAL   (United States)

^e UNIVERSITY OF MARYLAND GREENEBAUM CANCER CENTER   (United States)

^f Tower Cancer Research Foundation   (United States)

^g MEDSTAR RESEARCH INSTITUTE   (United States)

^h TEVA PHARMACEUTICALS   (Israel)

Author keywords

Apoptosis; Efficacy; Maximum tolerated dose; Non small cell lung cancer

Indexed keywords

DOCETAXEL; ERLOTINIB; GEFITINIB; OBATOCLAX; PACLITAXEL; RECOMBINANT GRANULOCYTE COLONY STIMULATING FACTOR;

ADULT; AGITATION; ALOPECIA; ANASARCA; ANEMIA; ANOREXIA; ANXIETY; ARTICLE; ATAXIA; BACKACHE; BRAIN ISCHEMIA; BRAIN METASTASIS; BRONCHOPNEUMONIA; CANCER COMBINATION CHEMOTHERAPY; CANCER RECURRENCE; CHILL; CLINICAL ARTICLE; CONFUSION; CONSTIPATION; COUGHING; DEHYDRATION; DIARRHEA; DIZZINESS; DRUG BLOOD LEVEL; DRUG DOSE REDUCTION; DRUG EFFICACY; DRUG SAFETY; DRUG TOLERABILITY; DRUG WITHDRAWAL; DYSGEUSIA; DYSPNEA; EMOTIONAL DISORDER; EUPHORIA; FATIGUE; FEBRILE NEUTROPENIA; FEVER; FLUSHING; FOLLOW UP; HALLUCINATION; HEADACHE; HUMAN; INSOMNIA; LEUKOPENIA; LUNG INFILTRATE; LUNG NON SMALL CELL CANCER; MAXIMUM TOLERATED DOSE; MULTIPLE CYCLE TREATMENT; NAUSEA; OPEN STUDY; PERIPHERAL EDEMA; PERIPHERAL NEUROPATHY; PHASE 1 CLINICAL TRIAL; PHASE 2 CLINICAL TRIAL; PLASMA CONCENTRATION-TIME CURVE; PRIORITY JOURNAL; PROGRESSION FREE SURVIVAL; SKIN DISEASE; SOMNOLENCE; SORE THROAT; THROMBOCYTOPENIA; VOMITING; YOUNG ADULT;

ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS; CARCINOMA, NON-SMALL-CELL LUNG; HUMANS; LUNG NEOPLASMS; MAXIMUM TOLERATED DOSE; NEOPLASM RECURRENCE, LOCAL; PYRROLES; TAXOIDS;

EID: 84891783231     PISSN: 15560864     EISSN: 15561380     Source Type: Journal    
DOI: 10.1097/JTO.0000000000000027     Document Type: Article

References (15)

1. Shepherd FA, Dancey J, Ramlau R, et al. Prospective randomized trial of docetaxel versus best supportive care in patients with non-small-cell lung cancer previously treated with platinum-based chemotherapy. J Clin Oncol 2000;18:2095-2103
2. Fossella FV, DeVore R, Kerr RN, et al. Randomized phase III trial of docetaxel versus vinorelbine or ifosfamide in patients with advanced nonsmall- cell lung cancer previously treated with platinum-containing chemotherapy regimens. The TAX 320 Non-Small Cell Lung Cancer Study Group. J Clin Oncol 2000;18:2354-2362
3. Berrieman HK, Smith L, OKane SL, Campbell A, Lind MJ, Cawkwell L. The expression of Bcl-2 family proteins differs between nonsmall cell lung carcinoma subtypes. Cancer 2005;103:1415-1419
4. Nguyen M, Marcellus RC, Roulston A, et al. Small molecule obatoclax (GX15-070) antagonizes MCL-1 and overcomes MCL-1-mediated resistance to apoptosis. Proc Natl Acad Sci USA 2007;104:19512-19517
5. Chiappori AA, Schreeder MT, Moezi MM, et al. A phase I trial of pan- Bcl-2 antagonist obatoclax administered as a 3-h or a 24-h infusion in combination with carboplatin and etoposide in patients with extensivestage small cell lung cancer. Br J Cancer 2012;106:839-845
6. Paik PK, Rudin CM, Brown A, et al. A phase I study of obatoclax mesylate, a Bcl-2 antagonist, plus topotecan in solid tumor malignancies. Cancer Chemother Pharmacol 2010;66:1079-1085
7. Paik PK, Rudin CM, Pietanza MC, et al. A phase II study of obatoclax mesylate, a Bcl-2 antagonist, plus topotecan in relapsed small cell lung cancer. Lung Cancer 2011;74:481-485
8. Therasse P, Arbuck SG, Eisenhauer EA, et al. New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst 2000;92:205-216
9. National Cancer Institute. Common Terminology Criteria for Adverse Events v3.0 (CTCAE). Available at: Http://ctep.cancer.gov/protocolDevelopment/ electronic-applications/docs/ctcaev3.pdf. Accessed December 17, 2012
10. Hwang JJ, Kuruvilla J, Mendelson D, et al. Phase I dose finding studies of obatoclax (GX15-070), a small molecule pan-BCL-2 family antagonist, in patients with advanced solid tumors or lymphoma. Clin Cancer Res 2010;16:4038-4045
11. Obrien 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 2009;113:299-305
12. Oki Y, Copeland A, Hagemeister F, et al. Experience with obatoclax mesylate (GX15-070), a small molecule pan-Bcl-2 family antagonist in patients with relapsed or refractory classical Hodgkin lymphoma. Blood 2012;119:2171-2172
13. Parikh SA, Kantarjian H, Schimmer A, et al. Phase II study of obatoclax mesylate (GX15-070), a small-molecule BCL-2 family antagonist, for patients with myelofibrosis. Clin Lymphoma Myeloma Leuk 2010;10:285-289
14. Schimmer AD, Obrien S, Kantarjian H, et al. A phase I study of the pan bcl-2 family inhibitor obatoclax mesylate in patients with advanced hematologic malignancies. Clin Cancer Res 2008;14:8295-8301
15. Hanna N, Shepherd FA, Fossella FV, et al. Randomized phase III trial of pemetrexed versus docetaxel in patients with non-small-cell lung cancer previously treated with chemotherapy. J Clin Oncol 2004;22:1589-1597