DOI: 10.1200/jco.2004.10.148. Phase I Study of G3139, a <i>bcl-2</i> Antisense Oligonucleotide, Combined With Carboplatin and Etoposide in Patients With Small-Cell Lung Cancer

Phase I Study of G3139, a bcl-2 Antisense Oligonucleotide, Combined With Carboplatin and Etoposide in Patients With Small-Cell Lung Cancer

10.1200/jco.2004.10.148

Crossref journal-article

American Society of Clinical Oncology (ASCO)

Journal of Clinical Oncology (233)

Abstract

Purpose Bcl-2 is expressed in the majority of cases of small cell lung cancer (SCLC) and may contribute to chemotherapeutic resistance. Bcl-2 suppression by G3139 (oblimersen sodium), a phosphorothioate oligonucleotide complementary to the bcl-2 mRNA, has the potential to enhance the antitumor efficacy of standard cytotoxic chemotherapy. A dose-finding study was performed evaluating the combination of G3139, carboplatin, and etoposide in patients with previously untreated extensive stage SCLC. Patients and Methods Sixteen patients were treated in three consecutive cohorts. Cohort 1 (n = 5) received G3139 5 mg/kg/d on days 1 to 8 of a 21 day cycle, with carboplatin area under the curve (AUC) = 6 on day 6, and etoposide 80 mg/m2/d on days 6 to 8. In cohort 2 (n = 4), carboplatin dose was reduced to AUC = 5. In cohort 3 (n = 7), G3139 dose was escalated to 7 mg/kg/d. G3139 plasma concentrations and Bcl-2 protein levels in peripheral blood mononuclear cells were evaluated. Results Two of three assessable patients in cohort 1 experienced cycle 1 dose-limiting toxicity (grade 4 neutropenia). No cycle 1 dose-limited toxicity was observed in cohorts 2 or 3. Of 14 patients assessable for response, partial response was documented in 12 patients (86%), and stable disease in two. Median time to progression was 5.9 months. Carboplatin and etoposide administration did not appear to alter G3139 pharmacokinetics. No evidence of Bcl-2 suppression in peripheral blood mononuclear cells was observed. Conclusion The combination of G3139, carboplatin, and etoposide is well tolerated and results in an encouraging response rate and time to progression in patients with extensive stage SCLC.

Bibliography

Rudin, C. M., Kozloff, M., Hoffman, P. C., Edelman, M. J., Karnauskas, R., Tomek, R., Szeto, L., & Vokes, E. E. (2004). Phase I Study of G3139, a bcl-2 Antisense Oligonucleotide, Combined With Carboplatin and Etoposide in Patients With Small-Cell Lung Cancer. Journal of Clinical Oncology, 22(6), 1110â1117.

Authors 8

Charles M. Rudin (first)
Mark Kozloff (additional)
Philip C. Hoffman (additional)
Martin J. Edelman (additional)
Robyn Karnauskas (additional)
Ronald Tomek (additional)
Livia Szeto (additional)
Everett E. Vokes (additional)

References 48 Referenced 133

10.3322/canjclin.52.1.23
10.1200/JCO.1999.17.6.1794
10.1200/JCO.1991.9.9.1627
10.1200/JCO.1989.7.9.1333
10.1200/JCO.1994.12.7.1427
Bunn PA Jr, Carney DN: Overview of chemotherapy for small cell lung cancer. Semin Oncol 24:S7,1997-69-S7-74, (2 suppl 7)
Sandler AB: Current management of small cell lung cancer. Semin Oncol 24:463,1997-476,
10.1093/oxfordjournals.annonc.a058931
Kosmidis PA, Samantas E, Fountzilas G, et al: Cisplatin/etoposide versus carboplatin/etoposide chemotherapy and irradiation in small cell lung cancer: A randomized phase III study. Hellenic Cooperative Oncology Group for Lung Cancer Trials. Semin Oncol 21:23,1994-30,
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Lotem J, Sachs L: Regulation by bcl-2, c-myc, and p53 of susceptibility to induction of apoptosis by heat shock and cancer chemotherapy compounds in differentiation-competent and -defective myeloid leukemic cells. Cell Growth Differ 4:41,1993-47,
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Walton MI, Whysong D, O'Connor PM, et al: Constitutive expression of human Bcl-2 modulates nitrogen mustard and camptothecin induced apoptosis. Cancer Res 53:1853,1993-1861,
Dole M, Nunez G, Merchant AK, et al: Bcl-2 inhibits chemotherapy-induced apoptosis in neuroblastoma. Cancer Res 54:3253,1994-3259,
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Dates

Type	When
Created	21 years, 5 months ago (March 12, 2004, 6:33 p.m.)
Deposited	3 years, 3 months ago (May 25, 2022, 4:49 p.m.)
Indexed	5 months ago (March 28, 2025, 6:59 a.m.)
Issued	21 years, 5 months ago (March 15, 2004)
Published	21 years, 5 months ago (March 15, 2004)
Published Print	21 years, 5 months ago (March 15, 2004)

Funders 0

None

BibTeX

@article{Rudin_2004, title={Phase I Study of G3139, a bcl-2 Antisense Oligonucleotide, Combined With Carboplatin and Etoposide in Patients With Small-Cell Lung Cancer}, volume={22}, ISSN={1527-7755}, url={http://dx.doi.org/10.1200/jco.2004.10.148}, DOI={10.1200/jco.2004.10.148}, number={6}, journal={Journal of Clinical Oncology}, publisher={American Society of Clinical Oncology (ASCO)}, author={Rudin, Charles M. and Kozloff, Mark and Hoffman, Philip C. and Edelman, Martin J. and Karnauskas, Robyn and Tomek, Ronald and Szeto, Livia and Vokes, Everett E.}, year={2004}, month=mar, pages={1110–1117} }

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