PSA and Clinical Responses to Celecoxib in a Patient With Prostate Cancer and Bone Metastases

Abstract

To the Editor: Cyclooxygenase 2 (COX-2) inhibitors have been shown to have activity against prostate cancer both in vitro and in vivo.1Liu XH Yao S Kirschenbaum A Levine AC NS398, a selective cyclooxygenase-2 inhibitor, induces apoptosis and down-regulates bcl-2 expression in LNCaP cells.Cancer Res. 1998; 58: 4245-4249PubMed Google Scholar, 2Hsu AL Ching TT Wang DS Song X Rangnekar VM Chen CS The cyclooxygenase-2 inhibitor celecoxib induces apoptosis by blocking Akt activation in human prostate cancer cells independently of Bcl-2.J Biol Chem. 2000; 275: 11397-11403Crossref PubMed Scopus (643) Google Scholar, 3Liu XH Kirschenbaum A Yao S Lee R Holland JF Levine AC Inhibition of cyclooxygenase-2 suppresses angiogenesis and the growth of prostate cancer in vivo.J Urol. 2000; 164: 820-825Abstract Full Text Full Text PDF PubMed Google Scholar We describe a patient with rapidly progressive hormone-refractory prostate cancer (HRPC) in whom celecoxib elicited a near-complete prostate-specific antigen (PSA) and clinical response. A 53-year-old man presented with dysuria and low back pain. A bone scan showed bony metastatic disease. The PSA level was 522 ng/mL, and a biopsy of the prostate revealed adenocarcinoma with a Gleason score of 9. A combination of bicalutamide and luteinizing hormone–releasing hormone was administered. The patient responded clinically, and the PSA value decreased to 4.04 ng/mL after 6 months of treatment. Nine months after initiation of antiandrogen therapy, the PSA level increased to 22.32 ng/mL and continued the upward trend to 37.46 ng/mL the following month. Both luteinizing hormone–releasing hormone and bicalutamide were discontinued to elicit a withdrawal response. During the 12th month, the PSA value increased to 58.44 ng/mL, and therapy with high-dose ketoconazole (200 mg 3 times daily) and hydrocortisone (20 mg/d) was instituted. A month later, the PSA level had increased to 79.78 ng/mL and was accompanied by worsening low back pain. The patient refused chemotherapy and bisphosphonates for HRPC. Celecoxib therapy was initiated at 200 mg/d, primarily for pain control. Clinical improvement was observed, with resolution of low back pain and decreased PSA values (Figure 1). Two months later, the PSA level had decreased to 5.48 ng/mL. Four months after initiation of celecoxib therapy, the PSA value increased to 11.52 ng/mL, and the celecoxib dose was increased to 200 mg twice daily. The PSA level was 10.4 ng/mL the following month, suggesting a dose response. Celecoxib was discontinued after 6 months because of continued elevation of the PSA value to 22.8 ng/mL accompanied by increasing back pain. To our knowledge, this is the first report of a near-complete PSA response of HRPC to celecoxib. The PSA and clinical responses in our patient with rapidly progressive HRPC show that celecoxib may be a useful addition to the therapeutic armamentarium for this disease. COX-2 inhibitors, including celecoxib, have been reported to have activity against prostate cancer both in vitro and in vivo.1Liu XH Yao S Kirschenbaum A Levine AC NS398, a selective cyclooxygenase-2 inhibitor, induces apoptosis and down-regulates bcl-2 expression in LNCaP cells.Cancer Res. 1998; 58: 4245-4249PubMed Google Scholar, 2Hsu AL Ching TT Wang DS Song X Rangnekar VM Chen CS The cyclooxygenase-2 inhibitor celecoxib induces apoptosis by blocking Akt activation in human prostate cancer cells independently of Bcl-2.J Biol Chem. 2000; 275: 11397-11403Crossref PubMed Scopus (643) Google Scholar, 3Liu XH Kirschenbaum A Yao S Lee R Holland JF Levine AC Inhibition of cyclooxygenase-2 suppresses angiogenesis and the growth of prostate cancer in vivo.J Urol. 2000; 164: 820-825Abstract Full Text Full Text PDF PubMed Google Scholar In a clinical trial of 24 patients with PSA-recurrent hormone-naive prostate cancer after definitive radiotherapy or radical prostatectomy, celecoxib (400 mg once or twice daily) slowed the rate of PSA increase and produced stabilization or a decrease of PSA in 11 patients.4Pruthi RS Derksen E A phase II trial of celecoxib in PSA recurrent prostate cancer after definitive radiation therapy or radical prostatectomy [abstract].J Clin Oncol. 2004; 23 (Abstract 4593.): 403Google Scholar In another clinical trial of 18 patients with HRPC, a combination of docetaxel chemotherapy and celecoxib (400 mg twice daily) produced PSA responses in 64.7%.5Kasimis B Cogswell J Hwang S et al.Phase II trial of docetaxel (D) and high-dose celecoxib (C) in patients (Pts) with hormone resistant prostate cancer (HRPC) [abstract].J Clin Oncol. 2004; 23 (Abstract 4616.): 409Google Scholar Despite recent reports of adverse cardiovascular events associated with COX-2 inhibitors, continued evaluation in advanced prostate cancer and other malignancies is probably a worthwhile endeavor in view of the frequent lack of effective options for these patients.