Oblimersen and α-interferon in metastatic renal cancer: A phase II study of the California Cancer Consortium

Kim Margolin, Timothy W. Synold, Primo N Lara, Paul Frankel, Simon F. Lacey, David I. Quinn, Tracey Baratta, Janice P. Dutcher, Bixin Xi, Don J. Diamond, David R Gandara

Research output: Contribution to journalArticle

14 Scopus citations

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 languageEnglish (US)
Pages (from-to)705-711
Number of pages7
JournalJournal of Cancer Research and Clinical Oncology
Volume133
Issue number10
DOIs
StatePublished - Oct 2007

Keywords

  • α-Interferon
  • G3139
  • Oblimersen
  • Phase II
  • Renal cancer

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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