Oblimersen in combination with temozolomide and albumin-bound paclitaxel in patients with advanced melanoma: a phase I trial

Purpose The combination of oblimersen, a bcl-2 antisense oligonucleotide, and dacarbazine lead to superior progression-free survival in advanced melanoma patients. Albumin-bound paclitaxel (nab-paclitaxel) has single-agent activity in melanoma. Methods In a phase I trial, chemotherapy-naïve patients with metastatic melanoma and normal LDH levels were enrolled on 3 cohorts. The treatment regimen consisted of 56-day cycles of oblimersen (7 mg/kg/day continuous IV infusion on day 1–7 and 22–28 in cohort 1 and 2; 900 mg fixed dose, twice weekly in weeks 1–2, 4–5 for cohort 3), temozolomide (75 mg/m 2 , days 1–42), and nab-paclitaxel (175 mg/m 2 in cohort 1 and 3, 260 mg/m 2 in cohort 2 on day 7 and 28). Apoptosis markers were tested in pre- and post-treatment specimens of a subset of patients. Results Six grade 3 events (neutropenia, renal insufficiency, hyponatremia, elevated creatinine, allergic reaction, and neuropathy) and 2 grade 4 events (neutropenia and thrombocytopenia) were seen in 32 patients. The objective response rate was 40.6 % (2 complete responses and 11 partial responses) and 11 patients had stable disease, for a disease control rate of 75 %. Conclusions The combination of oblimersen, temozolomide, and nab-paclitaxel was well tolerated and demonstrated encouraging activity in patients with advanced melanoma.