A phase II study of obatoclax mesylate, a Bcl-2 antagonist, plus topotecan in relapsed small cell lung cancer

Lung Cancer

Volumn 74, Issue 3, 2011, Pages 481-485

  Paik, Paul K ^a   Rudin, Charles M ^b   Pietanza, Maria C ^a   Brown, Andrew ^a   Rizvi, Naiyer A ^a   Takebe, Naoko ^c   Travis, William ^a   James, Leonard ^a   Ginsberg, Michelle S ^a   Juergens, Rosalyn ^b   Markus, Susan ^b   Tyson, Leslie ^a   Subzwari, Sara ^a   Kris, Mark G ^a   Krug, Lee M ^a  

^a MEMORIAL SLOAN KETTERING CANCER CENTER   (United States)

^b JOHNS HOPKINS UNIVERSITY   (United States)

^c NATIONAL CANCER INSTITUTE   (United States)

Author keywords

Apoptosis; Obatoclax mesylate; Small cell lung cancer (SCLC); Topotecan

Indexed keywords

OBATOCLAX; TOPOTECAN;

ADULT; AGED; ANEMIA; ARTICLE; ATAXIA; CANCER COMBINATION CHEMOTHERAPY; CLINICAL ARTICLE; CONSTIPATION; DIZZINESS; DRUG DOSE REDUCTION; DRUG EFFICACY; DRUG WITHDRAWAL; FATIGUE; FEMALE; HUMAN; LUNG SMALL CELL CANCER; MALE; MUCOSA INFLAMMATION; MULTIPLE CYCLE TREATMENT; NAUSEA; NEUTROPENIA; OPEN STUDY; OUTCOME ASSESSMENT; PHASE 2 CLINICAL TRIAL; PRIORITY JOURNAL; THROMBOCYTOPENIA; TREATMENT OUTCOME; TREATMENT RESPONSE;

AGED; ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS; CARCINOMA, SMALL CELL; DISEASE PROGRESSION; FEMALE; HUMANS; LUNG NEOPLASMS; MIDDLE AGED; PROTO-ONCOGENE PROTEINS C-BCL-2; PYRROLES; RECURRENCE; THROMBOCYTOPENIA; TOPOTECAN;

EID: 80051721210     PISSN: 01695002     EISSN: 18728332     Source Type: Journal    
DOI: 10.1016/j.lungcan.2011.05.005     Document Type: Article

References (25)

1. Govindan R., Page N., Morgensztern D., Read W., Tierney R., Vlahiotis A., et al. Changing epidemiology of small-cell lung cancer in the united states over the last 30 years: analysis of the surveillance, epidemiologic, and end results database. J Clin Oncol 2006, 24:4539-4544.
2. Jemal A., Siegel R., Ward E., Hao Y., Xu J., Thun M.J. Cancer statistics, 2009. CA Cancer J Clin 2009, 59:225-249.
3. Lally B.E., Urbanic J.J., Blackstock A.W., Miller A.A., Perry M.C. Small cell lung cancer: have we made any progress over the last 25 years?. Oncologist 2007, 12:1096-1104.
4. O'Brien M.E.R., Ciuleanu T.-E., Tsekov H., Shparyk Y., Cucevia B., Juhasz G., et al. Phase III trial comparing supportive care alone with supportive care with oral topotecan in patients with relapsed small-cell lung cancer. J Clin Oncol 2006, 24:5441-5447.
5. von Pawel J., Schiller J.H., Shepherd F.A., Fields S.Z., Kleisbauer J.P., Chrysson N.G., et al. Topotecan versus cyclophosphamide, doxorubicin, and vincristine for the treatment of recurrent small-cell lung cancer. J Clin Oncol 1999, 17:658.
6. Evans W., Shepherd F., Feld R., Osoba D., Dang P., Deboer G. VP-16 and cisplatin as first-line therapy for small-cell lung cancer. J Clin Oncol 1985, 3:1471-1477.
7. Jiang S., Sato Y., Kuwao S., Kameya T. Expression of bcl-2 oncogene protein is prevalent in small cell lung carcinomas. J Pathol 1995, 177:135-138.
8. Sartorius U., Krammer P. Upregulation of bcl-2 is involved in the mediation of chemotherapy resistance in human small cell lung cancer cell lines. Int J Cancer 2002, 97:584-592.
9. Ziegler A., Luedke G.H., Fabbro D., Altmann K.H., Stahel R.A., Zangemeister-Wittke U. Induction of apoptosis in small-cell lung cancer cells by an antisense oligodeoxynucleotide targeting the Bcl-2 coding sequence. J Natl Cancer Inst 1997, 89:1027-1036.
10. Zangemeister-Wittke U., Schenker T., Luedke G., Stahel R. Synergistic cytotoxicity of bcl-2 antisense oligodeoxynucleotides and etoposide, doxorubicin and cisplatin on small-cell lung cancer cell lines. Br J Cancer 1998, 78:1035-1042.
11. Kim Y.H., Girard L., Giacomini C.P., Wang P., Hernandez-Boussard T., Tibshirani R., et al. Combined microarray analysis of small cell lung cancer reveals altered apoptotic balance and distinct expression signatures of MYC family gene amplification. Oncogene 2005, 25:130-138.
12. GeminX. Investigator's brochure GX15-070MS. Malvern, PA; 2006.
13. Perez-Galan P., Roue G., Villamor N. The small molecule pan-Bcl-2 inhibitor GX15-070 induces apoptosis in vitro in mantle cell lymphoma (MCL) cells and exhibits a synergistic effect in combination with the proteasome inhibitor bortezomib. AACR 2006, A575.
14. Li J., Viallet J., Haura E. A small molecule pan-Bcl-2 family inhibitor, GX15-070, induces apoptosis and enhances cisplatin-induced apoptosis in non-small cell lung cancer cells. Cancer Chemother Pharmacol 2008, 61:525-534.
15. Paik P., Rudin C., Brown A., Rizvi N., Takebe N., Travis W., 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.
16. Schimmer A.D., O'Brien S., Kantarjian H., Brandwein J., Cheson B.D., Minden M.D., et al. Study of the pan Bcl-2 family inhibitor obatoclax mesylate in patients with advanced hematologic malignancies. Clin Cancer Res 2008, 14:8295-8301.
17. Hwang J.J., Kuruvilla J., Mendelson D., Pishvaian M.J., Deeken J.F., Siu L.L., 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.
18. von Pawel J., Gatzemeier U., Pujol J.-L., Moreau L., Bildat S., Ranson M., et al. Phase II comparator study of oral versus intravenous topotecan in patients with chemosensitive small-cell lung cancer. J Clin Oncol 2001, 19:1743-1749.
19. Ardizzoni A., Hansen H., Dombernowsky P., Gamucci T., Kaplan S., Postmus P., et al. Topotecan, a new active drug in the second-line treatment of small-cell lung cancer: a phase II study in patients with refractory and sensitive disease, The European Organization for Research and Treatment of Cancer Early Clinical Studies Group and New Drug Development Office, and the Lung Cancer Cooperative Group. J Clin Oncol 1997, 15:2090-2096.
20. Chiappori A., Schreeder M., Moezi M., Stephenson J., Blakely J., Salgia R., et al. A phase Ib trial of Bcl-2 inhibitor obatoclax in combination with carboplatin and etoposide for previously untreated patients with extensive-stage small cell lung cancer (ES-SCLC). J Clin Oncol 2009, 27:3576. [abstract].
21. Rudin C., Oliveira R., Garon E., Bonomi P., Camidge D., Nolan C., et al. A phase IIa study of ABT-263 in patients with relapsed small-cell lung cancer (SCLC). J Clin Oncol 2010, 28(Suppl.):7046. [abstract].
22. Baggstrom M., Govindan R., Koczywas M., Argiris A., Millward M., Johnson E., et al. Phase II, trial of R-(-)-gossypol acetic acid (NSC 726190, AT-101) in patients with recurrent extensive stage small cell lung cancer (ES-SCLC). J Clin Oncol 2010, (Suppl.):e17523. [abstract].
23. Leal T., Schelman W., Traynor A., Kolesar J., Marnocha R., Eickhoff J., et al. A phase I study of R-(-)-gossypol (AT-101, NSC 726190) in combination with cisplatin (P) and etoposide (E) in patients with advanced solid tumors and extensive-stage small cell lung cancer (ES-SCLC). J Clin Oncol 2010, (Suppl.):e13030. [abstract].
24. Chiappori A., Schreeder M., Moezi M., Stephenson J., Blakely J., Salgia R., et al. Optimizing obatoclax administration schedule: safety and efficacy of 3-hour versus 24-hour infusion in combination with carboplatin and etoposide for patients with extensive-stage small cell lung cancer (ES-SCLC). J Clin Oncol 2010, (Suppl.):e13531. [abstract].
25. Vogler M., Weber K., Dinsdale D., Schmitz I., Schulze-Osthoff K., Dyer M.J.S., et al. Different forms of cell death induced by putative BCL2 inhibitors. Cell Death Differ 2009, 16:1030-1039.