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Dacarbazine with or without oblimersen (a Bcl-2 antisense oligonucleotide) in chemotherapy-naive patients with advanced melanoma and low–normal serum lactate dehydrogenase: ‘The AGENDA trial’

Bedikian, Agop Y.a; Garbe, Clause; Conry, Robertb; Lebbe, Celestec; Grob, Jean J.dthe Genasense Melanoma Study Group

doi: 10.1097/CMR.0000000000000056
ORIGINAL ARTICLES: Clinical research

In a previous large randomized, open-label study, retrospective subset analysis revealed that the addition of the Bcl-2 antisense oligonucleotide oblimersen to dacarbazine (Dac) significantly improved overall survival, progression-free survival, and the response rate in chemotherapy-naive patients with advanced melanoma and normal baseline serum lactate dehydrogenase (LDH) levels. To confirm and expand on this observation, we conducted a prospective double-blind, placebo-controlled study to determine whether oblimersen augmented the efficacy of Dac in advanced melanoma patients with low–normal baseline LDH levels. A total of 314 chemotherapy-naive patients were randomly assigned to receive Dac (1000 mg/m2) preceded by a 5-day continuous intravenous infusion of either oblimersen sodium (7 mg/kg/day) or placebo every 21 days for less than eight cycles. Co-primary efficacy endpoints were overall survival and progression-free survival. Response and progression of the disease were assessed by independent blinded review of computed tomography scan images. No difference in overall nor progression-free survival was observed between the Dac–oblimersen and Dac–placebo groups. Although the overall (17.2 vs. 12.1%) and durable (10.8 vs. 7.6%) response rates numerically favored Dac–oblimersen over Dac–placebo, they did not differ significantly (P=0.19 and 0.32, respectively). The incidence of hematologic adverse events, particularly thrombocytopenia and neutropenia, was higher in the Dac–oblimersen group than in the Dac–placebo group. Withdrawals from the study because of treatment-related adverse events were low (i.e. <2.5%) in both groups. The addition of oblimersen to Dac did not significantly improve overall survival nor progression-free survival in patients with advanced melanoma and low–normal levels of LDH at baseline.

aDepartment of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas

bDivision of Hematology/Oncology, University of Alabama at Birmingham, Birmingham, Alabama, USA

cDermatology Polyclinic, Saint Louis Hospital, Paris

dDepartment of Dermatology, Aix-Marseille University, Marseille, France

eDepartment of Dermatology, University Medical Centre, Tubingen, Germany

Correspondence to Agop Y. Bedikian, MD, Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Unit 430, 1515 Holcombe Blvd., Houston, TX 77030, USA Tel: +1 713 792 2921; fax: +1 713 745 1046; e-mail:

Received November 6, 2013

Accepted January 27, 2014

© 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins