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

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 ≤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 ≤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 ≥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.