title: Oblimersen and alpha-interferon in metastatic renal cancer: a phase II study of the California Cancer Consortium.
abstract: OBJECTIVE
  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 alpha-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 alpha-IFN, 5 million units/m(2) 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 microg/ml and 0.15 +/- 0.07 l/h/kg, respectively.
  
  
  CONCLUSIONS
  Oblimersen given in this dose and schedule with alpha-IFN does not appear sufficiently active to warrant further study in advanced renal cancer. Combinations with newer targeted agents may show greater promise.
authors.affiliation: Division of Medical Oncology, City of Hope National Medical Center, 1500 East Duarte Road, Duarte, CA 91010-3000, USA. cabrown@coh.org
authors.forename: Kim
authors.initials: K
authors.lastname: Margolin
authors.forename: Timothy W
authors.initials: TW
authors.lastname: Synold
authors.forename: Primo
authors.initials: P
authors.lastname: Lara
authors.forename: Paul
authors.initials: P
authors.lastname: Frankel
authors.forename: Simon F
authors.initials: SF
authors.lastname: Lacey
authors.forename: David I
authors.initials: DI
authors.lastname: Quinn
authors.forename: Tracey
authors.initials: T
authors.lastname: Baratta
authors.forename: Janice P
authors.initials: JP
authors.lastname: Dutcher
authors.forename: Bixin
authors.initials: B
authors.lastname: Xi
authors.forename: Don J
authors.initials: DJ
authors.lastname: Diamond
authors.forename: David R
authors.initials: DR
authors.lastname: Gandara
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D005260:Female; D006801:Humans; D007155:Immunologic Factors / Q000008:administration & dosage / Q000009:adverse effects; D016898:Interferon-alpha / Q000008:administration & dosage* / Q000009:adverse effects; D007680:Kidney Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D013873:Thionucleotides / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics
chemical_list: D007155:Immunologic Factors; D016898:Interferon-alpha; D013873:Thionucleotides; C408162:oblimersen