Dataset Information

Phase II, randomized, placebo-controlled trial of neoadjuvant celecoxib in men with clinically localized prostate cancer: evaluation of drug-specific biomarkers.

ABSTRACT:

Purpose

Cyclooxygenase-2 (COX-2) is a potential pharmacologic target for the prevention of various malignancies, including prostate cancer. We conducted a randomized, double-blind trial to examine the effect of celecoxib on drug-specific biomarkers from prostate tissue obtained at prostatectomy.

Patients and methods

Patients with localized prostate cancer and Gleason sum > or = 7, prostate-specific antigen (PSA) > or = 15 ng/mL, clinical stage T2b or greater, or any combination with greater than 45% risk of capsular penetration were randomly assigned to celecoxib 400 mg by mouth twice daily or placebo for 4 to 6 weeks before prostatectomy. The primary end point was the difference in prostatic prostaglandin levels between the two groups. Secondary end points were differences in COX-1 and -2 expressions; oxidized DNA bases; and markers of proliferation, apoptosis and angiogenesis. Tissue celecoxib concentrations also were measured. Tertiary end points were drug safety and compliance.

Results

Seventy-three patients consented, and 64 were randomly assigned and included in the intention-to-treat analysis. There were no treatment differences in any of the primary or secondary outcomes. Multivariable regression revealed that tumor tissue had significantly lower COX-2 expression than benign prostatic tissue (P = .01) and significantly higher levels of the proliferation marker Ki-67 (P < .0001). Celecoxib was measurable in prostate tissue of patients on treatment, demonstrating that celecoxib reached its target. Celecoxib was safe and resulted in only grade 1 toxicities.

Conclusion

Treatment with 4 to 6 weeks of celecoxib had no effect on intermediate biomarkers of prostate carcinogenesis, despite the achievement of measurable tissue levels. We caution against using celecoxib 400 mg twice daily as a preventive agent for prostate cancer in additional studies.

SUBMITTER: Antonarakis ES

PROVIDER: S-EPMC2799055 | biostudies-literature | 2009 Oct

REPOSITORIES: biostudies-literature

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Publications

Phase II, randomized, placebo-controlled trial of neoadjuvant celecoxib in men with clinically localized prostate cancer: evaluation of drug-specific biomarkers.

Antonarakis Emmanuel S ES Heath Elisabeth I EI Walczak Janet R JR Nelson William G WG Fedor Helen H De Marzo Angelo M AM Zahurak Marianna L ML Piantadosi Steven S Dannenberg Andrew J AJ Gurganus Robin T RT Baker Sharyn D SD Parnes Howard L HL DeWeese Theodore L TL Partin Alan W AW Carducci Michael A MA

Journal of clinical oncology : official journal of the American Society of Clinical Oncology 20090831 30

<h4>Purpose</h4>Cyclooxygenase-2 (COX-2) is a potential pharmacologic target for the prevention of various malignancies, including prostate cancer. We conducted a randomized, double-blind trial to examine the effect of celecoxib on drug-specific biomarkers from prostate tissue obtained at prostatectomy.<h4>Patients and methods</h4>Patients with localized prostate cancer and Gleason sum > or = 7, prostate-specific antigen (PSA) > or = 15 ng/mL, clinical stage T2b or greater, or any combination wi ...[more]

PMID: 19720908

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Project description:BackgroundProstate cancer (PC) is the most commonly diagnosed noncutaneous malignancy in American men. PC, which exhibits a slow growth rate and multiple potential target epitopes, is an ideal candidate for immunotherapy. GVAX for prostate cancer is a cellular immunotherapy, composed of PC-3 cells (CG1940) and LNCaP cells (CG8711). Each of the components is a prostate adenocarcinoma cell line that has been genetically modified to secrete granulocyte-macrophage colony-stimulating factor. Hypothesizing that GVAX for prostate cancer could be effective in a neoadjuvant setting in patients with locally advanced disease, we initiated a phase II trial of neoadjuvant docetaxel and GVAX. For the trial, the clinical effects of GVAX were assessed in patients undergoing radical prostatectomy (RP).MethodsPatients received docetaxel administered at a dose of 75 mg/m(2) every 3 weeks for 4 cycles. GVAX was administered 2-3 days after chemotherapy preoperatively for four courses of immunotherapy. The first dose of GVAX was a prime immunotherapy of 5×10(8) cells. The subsequent boost immunotherapies consisted of 3×10(8) cells. After RP, patients received an additional six courses of immunotherapy. Pathologic complete response, toxicity, and clinical response were assessed. The primary endpoint of the trial was a pathologic state of pT0, which is defined as no evidence of cancer in the prostate.ResultsSix patients completed neoadjuvant docetaxel and GVAX therapy. No serious drug-related adverse events were observed. Median change in prostate-specific antigen (PSA) following neoadjuvant therapy was 1.47 ng/ml. One patient did not undergo RP due to the discovery of positive lymph nodes during exploration. Of the five patients completing RP, four had a downstaging of their Gleason score. Undetectable PSA was achieved in three patients at 2 months after RP and in two patients at 3 years after RP.ConclusionsNeoadjuvant docetaxel/GVAX is safe and well tolerated in patients with high-risk locally advanced PC. No evidence of increased intraoperative hemorrhage or increased length of hospital stay postoperatively was noted. These results justify further study of neoadjuvant immunotherapy.

Dataset Information

Phase II, randomized, placebo-controlled trial of neoadjuvant celecoxib in men with clinically localized prostate cancer: evaluation of drug-specific biomarkers.

Purpose

Patients and methods

Results

Conclusion

Publications

Phase II, randomized, placebo-controlled trial of neoadjuvant celecoxib in men with clinically localized prostate cancer: evaluation of drug-specific biomarkers.

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