Bcl-2 Antisense (oblimersen sodium) Plus Dacarbazine in Patients With Advanced Melanoma: The Oblimersen Melanoma Study Group

• Published in: Journal of clinical oncology Vol. 24; no. 29; pp. 4738 - 4745
• Main Authors: BEDIKIAN, Agop Y, MILLWARD, Michael, KIRKWOOD, John M, HALUSKA, Frank G, PEHAMBERGER, Hubert, CORNY, Robert, GORE, Martin, TREFZER, Uwe, PAVLICK, Anna C, DECONTI, Ronald, HERSH, Evan M, HERSEY, Peter
• Format: Journal Article
• Language: English
• Published: Baltimore, MD American Society of Clinical Oncology 10.10.2006; Lippincott Williams & Wilkins
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; Antineoplastic Agents, Alkylating - therapeutic use; Biological and medical sciences; Combined Modality Therapy; Dacarbazine - therapeutic use; Dermatology; Disease Progression; Drug Resistance, Neoplasm; Female; Humans; L-Lactate Dehydrogenase - blood; Male; Medical sciences; Melanoma - drug therapy; Melanoma - pathology; Middle Aged; Oligonucleotides, Antisense - therapeutic use; Proto-Oncogene Proteins c-bcl-2; Skin Neoplasms - drug therapy; Skin Neoplasms - pathology; Survival Analysis; Thionucleotides - therapeutic use; Treatment Outcome; Tumors; Tumors of the skin and soft tissue. Premalignant lesions; Antineoplastic agent; Human; Dacarbazine; Alkylating agent; Cancerology; Sodium; C-Onc gene; Malignant melanoma; Advanced stage; Malignant tumor; Oblimersen; Protooncogene
• ISSN: 0732-183X; 1527-7755
• DOI: 10.1200/JCO.2006.06.0483

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. 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. 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. 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.