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

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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.

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Acknowledgments

We thank all participating patients at the New York University Cancer Institute. This work was supported by Genta, Inc.; Abraxis BioScience, LLC.

Conflict of interest

None.

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Authors and Affiliations

  1. Division of Medical Oncology, NYU Cancer Institute, New York University School of Medicine, New York, NY, 10016, USA

    Patrick A. Ott, Jason Chang, Kathleen Madden, Rajni Kannan, Caroline Muren, Crystal Escano, Sandra Mendoza, Alex Gandhi, Leonard Liebes & Anna C. Pavlick

  2. Division of Biostatistics, New York University School of Medicine, New York, NY, 10016, USA

    Xin Cheng & Yongzhao Shao

  3. Melanoma Disease Center, Dana-Farber Cancer Institute, Harvard Medical School, 450 Brookline Ave, Boston, MA, 02215-5450, USA

    Patrick A. Ott

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  1. Patrick A. Ott
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Correspondence to Patrick A. Ott.

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Ott, P.A., Chang, J., Madden, K. et al. Oblimersen in combination with temozolomide and albumin-bound paclitaxel in patients with advanced melanoma: a phase I trial. Cancer Chemother Pharmacol 71, 183–191 (2013). https://doi.org/10.1007/s00280-012-1995-7

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