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

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.

• Authors: 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
• Journal: Cancer chemotherapy and pharmacology (Cancer Chemother Pharmacol) Vol. 71 Issue 1 Pg. 183-91 (Jan 2013) ISSN: 1432-0843 [Electronic] Germany
• PMID: 23064957 (Publication Type: Clinical Trial, Phase I, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

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