Authors: Kim Margolin Timothy W Synold Primo Lara Paul Frankel Simon F Lacey David I Quinn Tracey Baratta Janice P Dutcher Bixin Xi Don J Diamond David R Gandara
Publish Date: 2007/05/17
Volume: 133, Issue: 10, Pages: 705-711
Abstract
Oblimersen is an 18base oligodeoxynucleotide encoding antisense to the gene for bcl2 an antiapoptotic protein that is upregulated in renal and other cancers This study was designed to evaluate the combination of oblimersen with αInterferon in advanced renal cancer Trial endpoints were antitumor efficacy and toxicity pharmacokinetics and evidence of apoptosis in peripheral blood mononuclear cellsPatients 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 αIFN 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 agentsTwentythree patients were enrolled five of whom had prior systemic therapy three with prior highdose interleukin2 The median number of treatment cycles was 4 range 1–12 One patient had a partial response lasting 25 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 pretreatment and ontreatment levels of bcl2 or Annexin/PI positivity by flow cytometry Mean oblimersen steadystate plasma concentration and clearance was 23 ± 09 μg/ml and 015 ± 007 l/h/kg respectively
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