Cancer Chemotherapy and Pharmacology

, Volume 71, Issue 1, pp 183–191

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

  • Patrick A. Ott
  • Jason Chang
  • Kathleen Madden
  • Rajni Kannan
  • Caroline Muren
  • Crystal Escano
  • Xin Cheng
  • Yongzhao Shao
  • Sandra Mendoza
  • Alex Gandhi
  • Leonard Liebes
  • Anna C. Pavlick
Original Article

DOI: 10.1007/s00280-012-1995-7

Cite this article as:
Ott, P.A., Chang, J., Madden, K. et al. Cancer Chemother Pharmacol (2013) 71: 183. doi:10.1007/s00280-012-1995-7
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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/m2, days 1–42), and nab-paclitaxel (175 mg/m2 in cohort 1 and 3, 260 mg/m2 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.

Keywords

Albumin-bound paclitaxel Melanoma Neoplasm metastasis Oblimersen Temozolomide 

Copyright information

© Springer-Verlag Berlin Heidelberg 2012

Authors and Affiliations

  • Patrick A. Ott
    • 1
    • 3
  • Jason Chang
    • 1
  • Kathleen Madden
    • 1
  • Rajni Kannan
    • 1
  • Caroline Muren
    • 1
  • Crystal Escano
    • 1
  • Xin Cheng
    • 2
  • Yongzhao Shao
    • 2
  • Sandra Mendoza
    • 1
  • Alex Gandhi
    • 1
  • Leonard Liebes
    • 1
  • Anna C. Pavlick
    • 1
  1. 1.Division of Medical Oncology, NYU Cancer InstituteNew York University School of MedicineNew YorkUSA
  2. 2.Division of BiostatisticsNew York University School of MedicineNew YorkUSA
  3. 3.Melanoma Disease Center, Dana-Farber Cancer InstituteHarvard Medical SchoolBostonUSA