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

Cancer Chemother Pharmacol. 2013 Jan;71(1):183-91. doi: 10.1007/s00280-012-1995-7. Epub 2012 Oct 12.

Abstract

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.

Publication types

  • Clinical Trial, Phase I
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Albumin-Bound Paclitaxel
  • Albumins / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Apoptosis / drug effects*
  • Dacarbazine / administration & dosage
  • Dacarbazine / analogs & derivatives
  • Humans
  • Male
  • Melanoma / drug therapy*
  • Melanoma / pathology
  • Middle Aged
  • Neoplasm Metastasis
  • Oligonucleotides, Antisense / administration & dosage
  • Paclitaxel / administration & dosage
  • Skin Neoplasms / drug therapy*
  • Skin Neoplasms / pathology
  • Temozolomide
  • Thionucleotides / administration & dosage
  • Treatment Outcome

Substances

  • Albumin-Bound Paclitaxel
  • Albumins
  • Oligonucleotides, Antisense
  • Thionucleotides
  • Dacarbazine
  • oblimersen
  • Paclitaxel
  • Temozolomide