Docetaxel plus oblimersen sodium (Bcl-2 antisense oligonucleotide): an EORTC multicenter, randomized phase II study in patients with castration-resistant prostate cancer

Ann Oncol. 2009 Jul;20(7):1264-9. doi: 10.1093/annonc/mdn784. Epub 2009 Mar 17.

Abstract

Background: This randomized, phase II study assessed the activity of oblimersen sodium, a Bcl-2 antisense oligonucleotide, administered before docetaxel (Taxotere) to patients with castration-resistant prostate cancer.

Patients and methods: Chemotherapy-naive patients with prostate-specific antigen (PSA) progression and testosterone < or = 0.5 ng/ml received docetaxel 75 mg/m2 on day 1 or oblimersen 7 mg/kg/day continuous i.v. infusion on days 1-7 with docetaxel 75 mg/m2 on day 5 every 3 weeks for < or = 12 cycles. Primary end points were confirmed PSA response (Bubley criteria) and major toxic events.

Results: Confirmed PSA response was observed in 46% and 37% of 57 and 54 patients treated with docetaxel and docetaxel-oblimersen, respectively. Partial response (RECIST) was achieved in 18% and 24%, respectively. Oblimersen added to docetaxel was associated with an increase in the incidence of grade > or = 3 fatigue, mucositis, and thrombocytopenia. Major toxic events were reported in 22.8% and 40.7% of patients with docetaxel and docetaxel-oblimersen, respectively.

Conclusions: The primary end points of the study were not met: a rate of confirmed PSA response >30% and a major toxic event rate <45% were not observed with docetaxel-oblimersen.

Trial registration: ClinicalTrials.gov NCT00085228.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Castration
  • Docetaxel
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Humans
  • Infusions, Intravenous
  • Male
  • Middle Aged
  • Prostate-Specific Antigen
  • Prostatic Neoplasms / drug therapy*
  • Prostatic Neoplasms / pathology
  • Taxoids / administration & dosage
  • Thionucleotides / administration & dosage
  • Treatment Outcome

Substances

  • Taxoids
  • Thionucleotides
  • Docetaxel
  • oblimersen
  • Prostate-Specific Antigen

Associated data

  • ClinicalTrials.gov/NCT00085228