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

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.

• Authors: C N Sternberg, H Dumez, H Van Poppel, I Skoneczna, A Sella, G Daugaard, T Gil, J Graham, P Carpentier, F Calabro, L Collette, D Lacombe, EORTC Genitourinary Tract Cancer Group
• Journal: Annals of oncology : official journal of the European Society for Medical Oncology (Ann Oncol) Vol. 20 Issue 7 Pg. 1264-9 (Jul 2009) ISSN: 1569-8041 [Electronic] England
• PMID: 19297314 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

• 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, pathology)
• Taxoids (administration & dosage)
• Thionucleotides (administration & dosage)
• Treatment Outcome