Department of Surgery, Universite de Montreal, Centre Hospitalier de l'Université de Montréal (CHUM) and Institut du cancer de Montréal, 1560 Sherbrooke Est, Montréal, Quebéc, H2L 2W5, Canada.
Clusterin (CLU) is an anti-apoptotic, stress-induced protein conferring treatment resistance when overexpressed. This study tested custirsen, a CLU inhibitor, in patients with metastatic castration-resistant prostate cancer (mCRPC) progressing during or within six months of initial docetaxel therapy.
Men were randomized to receive either docetaxel+prednisone+custirsen (DPC) or mitoxantrone+prednisone+custirsen (MPC).
Forty-two patients received study treatment. Toxicity was similar in both arms. Twenty patients treated with DPC received a median of eight cycles; overall survival was 15.8 months. Median time to pain progression (TTPP) was 10.0 months; 10 of 13 (77%) evaluable patients had pain responses. Three of 13 (23%) evaluable patients had objective partial responses. PSA declines of ≥90%, ≥50%, and ≥30% occurred in 4 (20%), 8 (40%) and 11 (55%) patients, respectively. Twenty-two patients treated with MPC received a median of six cycles; overall survival was 11.5 months. The median TTPP was 5.2 months; 6 of 13 (46%) evaluable patients had pain responses. No objective responses were observed. PSA declines of ≥50% and ≥30% occurred in 6 (27%) and 7 (32%) patients, respectively. Low serum CLU levels during treatment showed superior survival for patients using modeling with proportional hazard regression with a time-dependent covariate and different landmarks.
Custirsen plus either docetaxel or mitoxantrone was feasible in patients with progressive mCRPC following first-line docetaxel therapy. Pain relief was higher than expected, with interesting correlations between serum CLU and survival. A phase 3 trial evaluating the pain palliation benefit of custirsen with taxane therapy is ongoing.
Written by:
Saad F, Hotte S, North S, Eigl B, Chi KN, Czaykowski P, Wood L, Pollack M, Berry SR, Lattouf JB, Mukherjee SD, Gleave ME, Winquist E. Are you the author?
Reference: Clin Cancer Res. 2011 Jul 25. Epub ahead of print.
doi: 10.1158/1078-0432.CCR-11-0859
PubMed Abstract
PMID: 21788353
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