Abstract
Purpose: Oblimersen is an 18-base oligodeoxynucleotide encoding antisense to the gene for bcl-2, an anti-apoptotic protein that is upregulated in renal and other cancers. This study was designed to evaluate the combination of oblimersen with α-Interferon in advanced renal cancer. Trial endpoints were antitumor efficacy and toxicity, pharmacokinetics, and evidence of apoptosis in peripheral blood mononuclear cells. Methods: Patients with measurable advanced renal cancer and 0-1 prior therapy were eligible. Treatment consisted of oblimersen, 7 mg/kg/day, as a continuous intravenous infusion 7 days of every 14 day cycle, plus α-IFN, 5 million units/m2 subcutaneously, days 4 and 6 of the first oblimersen infusion, then thrice weekly. Blood for laboratory correlates was collected before treatment, during oblimersen, and during therapy with both agents. Results: Twenty-three patients were enrolled, five of whom had prior systemic therapy (three with prior high-dose interleukin-2). The median number of treatment cycles was 4 (range 1-12). One patient had a partial response lasting 2.5 months. The Grade 3-4 toxicities were fatigue, fever, myelosuppression, hepatic enzyme and metabolic abnormalities. Laboratory analyses of CD3+ lymphocyte apoptotic markers demonstrated no change between pre-treatment and on-treatment levels of bcl-2 or Annexin/PI positivity by flow cytometry. Mean oblimersen steady-state plasma concentration and clearance was 2.3 ± 0.9 μg/ml and 0.15 ± 0.07 l/h/kg, respectively. Conclusions: Oblimersen given in this dose and schedule with α-IFN does not appear sufficiently active to warrant further study in advanced renal cancer. Combinations with newer targeted agents may show greater promise.
Original language | English (US) |
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Pages (from-to) | 705-711 |
Number of pages | 7 |
Journal | Journal of Cancer Research and Clinical Oncology |
Volume | 133 |
Issue number | 10 |
DOIs | |
State | Published - Oct 2007 |
Keywords
- α-Interferon
- G3139
- Oblimersen
- Phase II
- Renal cancer
ASJC Scopus subject areas
- Cancer Research
- Oncology