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Originally published as JCO Early Release 10.1200/JCO.2006.06.0483 on September 11 2006

Journal of Clinical Oncology, Vol 24, No 29 (October 10), 2006: pp. 4738-4745
© 2006 American Society of Clinical Oncology.
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Bcl-2 Antisense (oblimersen sodium) Plus Dacarbazine in Patients With Advanced Melanoma: The Oblimersen Melanoma Study Group

Agop Y. Bedikian, Michael Millward, Hubert Pehamberger, Robert Conry, Martin Gore, Uwe Trefzer, Anna C. Pavlick, Ronald DeConti, Evan M. Hersh, Peter Hersey, John M. Kirkwood, Frank G. Haluska

From the University of Texas M.D. Anderson Cancer Center, Houston, TX; Sydney Cancer Centre and Sydney Melanoma Unit, Sydney, Australia; Division of General Dermatology, Medical University of Vienna, Vienna, Austria; University of Alabama at Birmingham, Hematology/Oncology, Birmingham, AL; Royal Marsden Hospital, London, United Kingdom; Klinik fur Dermatologie, Venerologie, und Allergologie mit Asthmapoliklinik, Charité Universitätsmedizin Berlin, Berlin, Germany; New York University School of Medicine, New York, NY; H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL; Arizona Cancer Center, Tucson, AZ; Newcastle Mater Misericordiae Hospital, Waratah, Australia; University of Pittsburgh Cancer Institute, Pittsburgh, PA; and Tufts-New England Medical Center, Boston, MA

Address reprint requests to Frank G. Haluska, MD, PhD, Tufts-New England Medical Center, 750 Washington St, Box 6626, Boston, MA 02111; e-mail: FHaluska{at}tufts-nemc.org

PURPOSE: Chemotherapy resistance in melanoma has been linked to antiapoptotic effects mediated by Bcl-2 protein. We evaluated whether targeting Bcl-2 using an antisense oligonucleotide (oblimersen sodium) could improve the efficacy of systemic chemotherapy in patients with advanced melanoma.

PATIENTS AND METHODS: We randomly assigned chemotherapy-naïve patients with advanced melanoma to treatment with dacarbazine (1,000 mg/m2) alone or preceded by a 5-day continuous intravenous infusion of oblimersen sodium (7 mg/kg/d) every 3 weeks for up to eight cycles. Patients were stratified by Eastern Cooperative Oncology Group performance status, liver metastases, disease site, and serum lactate dehydrogenase (LDH). The primary efficacy end point was overall survival.

RESULTS: Among 771 patients randomly assigned, the addition of oblimersen to dacarbazine yielded a trend toward improved survival at 24-month minimum follow-up (median, 9.0 v 7.8 months; P = .077) and significant increases in progression-free survival (median, 2.6 v 1.6 months; P < .001), overall response (13.5% v 7.5%; P = .007), complete response (2.8% v 0.8%), and durable response (7.3% v 3.6%; P = .03). A significant interaction between baseline serum LDH and treatment was observed; oblimersen significantly increased survival in patients whose baseline serum LDH was not elevated (median overall survival, 11.4 v 9.7 months; P = .02). Neutropenia and thrombocytopenia were increased in the oblimersen-dacarbazine group; however, there was no increase in serious infections or bleeding events.

CONCLUSION: The addition of oblimersen to dacarbazine significantly improved multiple clinical outcomes in patients with advanced melanoma and increased overall survival in patients without an elevated baseline serum LDH.

published online ahead of print at www.jco.org on September 11, 2006.

Supported by Genta, Inc.

Presented in part at the 41st Annual Meeting of the American Society of Clinical Oncology, Orlando, FL, May 13-17, 2005.

Terms in blue are defined in the glossary, found at the end of this article and online at www.jco.org.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.


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Related Editorial

  • Reaching First Base in the Treatment of Metastatic Melanoma
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    JCO 2006 24: 4673-4674 [Full Text]

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  • Molecular Classification of Patients With Malignant Melanoma for New Therapeutic Strategies
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  • Molecular Classification of Patients With Malignant Melanoma for New Therapeutic Strategies
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