celecoxib, Celebrex
Effect of celecoxib on capecitabine-induced hand-foot syndrome and antitumor activity.

Lin E, Morris JS, Ayers GD.

Division of Gastrointestinal Oncology, University of Texas M. D. Anderson Cancer Center, Houston, Texas, USA.

We hypothesized that hand-foot syndrome is an inflammatory phenomenon mediated by the overexpression of cyclooxygenase 2 (COX-2). Therefore, a specific COX-2 inhibitor such as celecoxib (Celebrex) could attenuate both the incidence and severity of hand-foot syndrome. We undertook a retrospective study comparing the incidences of hand-foot syndrome in 67 patients with metastatic colorectal cancer who took capecitabine (Xeloda) with or without celecoxib. Surprisingly, celecoxib seemed to attenuate capecitabine-induced diarrhea as well. Capecitabine/celecoxib was also associated with increased tumor response, proportion of stable disease (62.5% vs 22.8%, P = .001), and increase in median time to tumor progression (6 vs 3 months, P = .002) compared with capecitabine alone, despite the fact that patients on capecitabine/celecoxib had less favorable disease characteristics (age, performance status, and prior chemotherapies). Overexpression of COX-2, implicated in promoting angiogenesis, enhanced tumor invasiveness, evasion of apoptosis, and immune suppression, is a bona fide molecular target for many solid tumors, including colorectal cancer. Combining capecitabine with celecoxib in the treatment of colorectal cancer has strong preclinical rationales. A prospective study is being designed to evaluate capecitabine and celecoxib with or without epidermal growth factor receptor antagonist ZD1839 in the frontline treatment of metastatic colorectal cancer. These regimens under study are orally based and may significantly impact quality of life in the frontline treatment of metastatic colorectal cancer.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12520638&dopt=Abstract celecoxib, Celebrex



celecoxib, Celebrex
American pain society pain questionnaire and other pain measures in the assessment of osteoarthritis pain: a pooled analysis of three celecoxib pivotal studies.

Moskowitz RW, Sunshine A, Brugger A, Lefkowith JB, Zhao WW, Geis GS.

Case Western Reserve University School of Medicine, Cleveland, OH, USA. rolliemoskowitz aol.com

The aim of this study was to evaluate the utility of the American Pain Society (APS) questionnaire in the assessment of osteoarthritis (OA) pain and to determine the onset of action of celecoxib in the treatment of acute flare pain in patients with OA of the knee or hip. Pooled data from three pivotal, randomized, double-blind, placebo-controlled, 12-week trials of patients with OA who exhibited a flare of disease activity after withdrawal of nonsteroidal anti-inflammatory drug or analgesic therapy were evaluated. Patients completed the APS Pain Measure Questionnaire, which evaluates pain intensity and quality of life, at baseline and daily for the first 7 days of therapy. In addition, patients underwent a range of standard OA assessments to evaluate the analgesic efficacy of celecoxib up to 12 weeks. Three thousand two hundred fifty-eight patients were enrolled in the three studies, of whom 2041 completed the APS questionnaire (1010 received celecoxib, 513 received naproxen, and 518 received placebo). Within the first 24 hours, celecoxib at a dose of 200 or 400 mg/d significantly reduced the amount of acute pain experienced compared with placebo for four of the five measures, and statistical significance for the remaining parameter, "pain in the last 24 hours," was achieved on day 2. Celecoxib at a dose of 200 to 400 mg/d provided similar efficacy to naproxen at a dose of 1000 mg/d. The pain relief observed with celecoxib was maintained for the APS evaluation period. Long-term efficacy assessments showed the efficacy of 200 mg/d of celecoxib to be continuous and maintained for at least the 12 weeks of the study and that it was equivalent to 400 mg/d of celecoxib and 1000 mg/d of naproxen. This study demonstrates that the APS questionnaire is a useful measure of pain and therapeutic response in OA. Celecoxib furthermore seems to be an effective acute and chronic analgesic in OA.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12522515&dopt=Abstract celecoxib, Celebrex



celecoxib, Celebrex
Effect of the selective COX-2 inhibitors, celecoxib and rofecoxib in rat acute models of inflammation.

Pinheiro RM, Calixto JB.

Department of Pharmacology, Centre of Biological Sciences, Universidade Federal de Santa Catarina, 88015-420, Florianopolis, SC, Brazil.

OBJECTIVE: This study evaluates the action of celecoxib and rofecoxib, two selective cyclooxygenase-2 (COX-2) inhibitors in two acute models of inflammation, carrageenan (Cg)-induced rat pleurisy, and paw oedema formation. MATERIAL: Male Wistar rats (N = 4-10 per group) were used. A fixed volume of PBS or carrageenan was injected into the pleural cavity or into the paw. Furthermore, the myeloperoxidase (MPO) activity and the levels of nitrite/nitrate (NOx), interleukin-1beta (IL-1beta), tumor necrosis factor-a (TNF-a) and PGE2 were also assessed in the paw tissue or in pleural exudate. RESULTS: Dexamethasone (DEX, 0.5 mg kg(-1), s.c., -4 h) and indomethacin (INDO, 3 mg kg(-1), p.o., -1 h) suppressed Cg-induced pleural exudate accumulation by 84 and 77% and inflammatory cell influx by 66 and 47%, respectively. In contrast, celecoxib (CLX, 10 mg kg(-1), p.o., -1 h) or rofecoxib (RFX, 10 mg kg(-1) , p.o., -1 h) only reduced the Cg-induced pleural exudate volume by 44 and 40%, respectively, but had no significant effect over inflammatory cell influx. At the same doses used for pleurisy, DEX, INDO, CLX, RFX and SC-560 (a selective COX-1 inhibitor, 40 mg kg(-1), p.o., -1 h), inhibited the Cg-induced paw oedema by 49, 31, 21, 21 and 17%. DEX, INDO or SC-560 reduced the level of MPO by 71, 78 and 59%, while CLX or RFX produced a small, but significant increase (28 or 16%) in MPO activity. In the rat model of pleurisy, PGE2 levels in cell-free exudates were significantly attenuated by 91, 89, 57 and 65% in animals treated with DEX, INDO, CLX or RFX. In contrast, INDO reduced significantly the whole bloodTXB, synthesis (59%) while DEX and INDO reduced the pleural content of NOx significantly. Treatment of animals with CLX or RFX did not alter the content of pro-inflammatory cytokines IL-1beta or TNF-alpha in the pleural exudate, but CLX reduced IL-1beta levels in the rat paw tissue and RFX increased TNF-alpha in this tissue. CONCLUSION: Together these results provide consistent evidence indicating that the selective COX-2 inhibitors CLX and RFX, in contrast to DEX, INDO or SC-560, despite reducing greatly the Cg-induced pleural exudation, PGE2 content and paw oedema have only partial acute anti-inflammatory properties in two different rat acute models of inflammation.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12558194&dopt=Abstract celecoxib, Celebrex



celecoxib, Celebrex
The biochemical selectivity of novel COX-2 inhibitors in whole blood assays of COX-isozyme activity.

Tacconelli S, Capone ML, Sciulli MG, Ricciotti E, Patrignani P.

Division of Pharmacology, Department of Medicine and Center of Excellence on Aging, G. D'Annunzio University School of Medicine, 66013 Chieti, Italy.

We have evaluated the biochemical selectivity of novel cyclo-oxygenase (COX)-2 inhibitors, etoricoxib, valdecoxib, DFU and DFP, vs rofecoxib and celecoxib, using the human whole blood assays of COX-isozyme activity, in vitro. Compounds were incubated with human whole blood samples, allowed to clot for 1 h at 37 degrees C, or stimulated with lipopolysaccharide (10 microg/ml) for 24 h at 37 degrees C. Serum thromboxane (TX) B2 and plasma prostaglandin (PG) E2 levels were measured by specific radioimmunoassays as indices of platelet COX-1 and monocyte COX-2 activity, respectively. Valdecoxib, etoricoxib, DFU and DFP inhibited platelet COX-1 and monocyte COX-2 with the following COX-1/COX-2 IC50 ratios: 61.5, 344, 660 and 1918, respectively. The reference compounds, celecoxib and rofecoxib had corresponding values of 29.6 and 272. In conclusion, a second wave of COX-2 inhibitors with higher biochemical selectivity than the existing coxibs has been developed. Whether their administration will be associated with improved clinical efficacy and/or safety vis-a-vis celecoxib and rofecoxib remains to be established.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12564662&dopt=Abstract celecoxib, Celebrex



celecoxib, Celebrex
Reduction of scar formation in full-thickness wounds with topical celecoxib treatment.

Wilgus TA, Vodovotz Y, Vittadini E, Clubbs EA, Oberyszyn TM.

Department of Pathology, The Ohio State University, Columbus, Ohio 43210, USA.

Adult wound repair occurs with an initial inflammatory response, reepithelialization, and the formation of a permanent scar. Although the inflammatory phase is often considered a necessity for successful adult wound healing, fetal healing studies have shown the ability to regenerate skin and to heal wounds in a scarless manner in the absence of inflammation. The cyclooxygenase-2 (COX-2) enzyme, a known mediator of inflammation, has been shown to contribute to a variety of inflammatory conditions and to the development of cancer in many organs. To examine the role of COX-2 in the wound healing process, incisional wounds were treated topically with the anti-inflammatory COX-2 inhibitor celecoxib. Acutely, celecoxib inhibited several parameters of inflammation in the wound site. This decrease in the early inflammatory phase of wound healing had a significant effect on later events in the wound healing process, namely a reduction in scar tissue formation, without disrupting reepithelialization or decreasing tensile strength. Our data suggest that in the absence of infection, adult wound healing is able to commence with decreased inflammation and that anti-inflammatory drugs may be used to improve the outcome of the repair process in the skin by limiting scar formation.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12581424&dopt=Abstract celecoxib, Celebrex



celecoxib, Celebrex
Intracranial inhibition of glioma cell growth by cyclooxygenase-2 inhibitor celecoxib.

Nam DH, Park K, Park C, Im YH, Kim MH, Lee S, Hong SC, Shin HJ, Kim JH, Eoh W, McDonnell TJ.

Department of Neurosurgery, Samsung Medical Center and Biomedical Research Institute, Sungkyunkwan University School of Medicine, Seoul 135-710, Korea. nsnam smc.samsung.co.kr

Higher cyclooxygenase-2 (COX-2) expression is clinically associated with more aggressive gliomas and is a strong predictor of poor survival. To determine whether oral administration of a COX-2-specific inhibitor can inhibit glial tumors, we analyzed the effect of celecoxib on the growth of 9L rat gliosarcoma cells that were orthotopically transplanted into rat brains. Oral administration of celecoxib beginning 1 day after implantation of 5 x 10(4) 9L rat gliosarcoma cells into rat brain reduced the incidence and size of tumors significantly. Immunohistochemical analysis of implanted gliosarcoma cells from rats treated with celecoxib showed lower levels of phospho-Akt, phospho-EGFR, Bcl-2, and Bcl-XL expression compared with untreated tumor cells. Gliosarcoma cells from treated rats had significantly more TUNEL- and caspase-3-positive cells and fewer PCNA-positive cells. These results demonstrate that selective COX-2 inhibitors may be useful as adjuvants and/or therapeutic agents to treat gliomas overexpressing COX-2.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14719052&dopt=Abstract celecoxib, Celebrex



celecoxib, Celebrex
Cancer "photo-chemoprevention" with pulsed dye laser and celecoxib.

Wang Z, Fuentes CF, Shapshay SM.

Department of Otolaryngology Head and Neck Surgery, Boston Medical Center/Boston University School of Medicine, Massachusetts 02118, USA. zwang bu.edu

BACKGROUND AND OBJECTIVES: Our previous study demonstrated the efficacy of pulsed dye laser (PDL) in inhibiting cancer growth. This study is to determine the synergic effect of PDL and Celecoxib, when they are combined for treatment of oral cancer. STUDY DESIGN/MATERIALS AND METHODS: Fifteen mice were inoculated with oral cell carcinoma and divided into three groups of five each (30 seeding sites/group): (1) control (no treatment), (2) PDL only, and (3) treatment with combined PDL and Celecoxib (1,500 ppm). The number and volume of tumors were counted and measured for 21 days. RESULTS: The combined treatment developed tumor at the slowest rate. On day 21, the average tumor volumes were (1) 483.6 mm(3) (control), (2) 312.1 mm(3) (PDL only), and (3) 151.4 mm(3) (combined treatment). CONCLUSIONS: A synergic effect was found in the combined treatment group. This study provides the first evidence of the efficacy of a new strategy for the treatment of oral cancer, namely, cancer "photo-chemoprevention." Copyright 2003 Wiley-Liss, Inc.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12605423&dopt=Abstract celecoxib, Celebrex