Abraxane, temozolomide, and oblimersen (The ATG Trial): A final report of toxicity and clinical efficacy in metastatic melanoma patients with normal lactate dehydrogenase (LDH).

8545 Background: The combination (combo) of oblimersen (OBL), a bcl-2 anti-sense agent, with dacarbazine showed promise in metastatic melanoma (MM) patients (pts) with normal (nl) LDH. OBL, temozolomide (TMZ), and abraxane (ABX) were synergistic in preclinical models of A375 MM cell lines. We conducted a phase I trial of this combo in MM pts with nl LDH and will present the final analysis of toxicity (tox) and clinical efficacy. Methods: Chemo-naive MM pts (ECOG PS≤2, nl LDH, measurable disease per RECIST) were enrolled onto a phase I protocol with 3 cohorts (ct). Treatment regimen consisted of 56-day cycles of OBL 7 mg/kg/d continuous IV infusion (CIV), d 1-7 and 22-28 in ct 1-2; OBL 900 mg fixed dose over 1 hour, twice weekly in weeks 1-2, 4-5 [d 1,4,8,11,22,25,29,32] for ct 3; TMZ 75/m2/d in ct 1-3, d 1-42, and ABX 175 mg/m2 in ct 1 and 3, 260 mg/m2 in ct 2, d 7 and 28. IHC staining for Bcl-2, Bcl-XL, BAK and caspase 3 were performed in pre- and post-therapy tumor samples. ABX and OBL PK and shed serum...