Cancer, treatment celecoxib

Celecoxib is not approved by the FDA for the treatment of cancers. However, celecoxib as monotherapy or as part of combination therapy has been demonstrated to suppress tumor growth in a variety of neoplasms and has benefited patients with prostate cancer. Potential mechanisms of anticancer activity of celecoxib include inhibition of endogenous carcinogen formation, modulation of inflammation, increased cellular sensitivity to apoptosis, and inhibition of angiogenesis[l]. 

Selective COX-2 inhibitors have also been shown to prevent early and late forms of colorectal neoplasia in rat models. Reddy et al. showed that administration of celecoxib inhibited aberrant colonic crypt foci (ACF) induction and multiplicity by about 40-49% in an azoxymethane-induced ACF rat model (81). Later the same investigators also showed that dietary administration of celecoxib can inhibit both the incidence and multiplicity of colon tumors by about 93 % and 97 %, respectively in the same rat model (82). Other researchers reported similar results with the Min mouse model (52). There is little data on human clinical trials with selective COX-2 inhibitors for colorectal tumor prevention. Recently Steinbach et al. conducted a double-blind, placebo-controlled study with 77 patients with FAP, and reported that treatment with celecoxib, a selective COX-2 inhibitor, for 6 mo led to a significant reduction (28%) in the number of colorectal polyps in these patients (50). Collectively, COX-2 nonspecific or specific NSAIDs appear to have chemopreventive activity against colorectal cancer development. Selective... 

Celecoxib has been approved for the treatment of osteoarthritis and rheumatoid arthritis, and rofecoxib has been approved for the treatment of osteoarthritis, acute pain and primary dysmenorrhea. Celecoxib and rofecoxib do not appear to differ in efficacy for the treatment of osteoarthritis. However, neither drug has efficacy greater than that of the non-selective NSAIDs. Since the COX-2 enzyme appears to play an important role in colon cancer the COX-2 inhibitors may find future uses in the treatment or prevention of colorectal cancer. 

The two COX-2 selective inhibitors, celecoxib (1) and rofecoxib (2), marketed in 1999 and 2000, respectively, have quickly become blockbuster drugs (with annual sales of more than one billion dollars) for the treatment of osteoarthritis (OA) and rheumatoid arthritis (RA). Many backups and competition drugs are sure to follow. Excitingly, some COX-2 selective inhibitors have been shown to inhibit cancer growth as well. ... 

Howe et al. (425) reviewed the potential of using COX-2 inhibitors for the treatment of breast cancer and suggested that there is good rationale to examine COX-2 inhibition for breast cancer prevention. Limited data are available in animal models of breast cancer however, Harris et al. (426) showed that celecoxib inhibited the tumor multiplicity by 86% and the incidence by 68%. 

North, G.L., Celecoxib as adjunctive therapy for treatment of colorectal cancer,H . Pharmacother., 35, 1638-1643,2001. 

Fig. 7. Susceptibility of prostate cancer cells to celecoxib-induced apoptosis is independent of cyclooxygenase-2 (COX-2) expression levels. (A, left panel) Effect of 50 pM celecoxib on the viability of parental PC-3 cells and the COX-2-deficient clone 2 F6. (A, right panel) Effect of 50 pM celecoxib on the viability of the COX-2 antisense clone 7D9 with (+) or without (-) a doxycycline (Dox) pretreatment (2 pg/mL). Data represent means 95% confidence intervals (error bars) (n = 3). (B) Effect of celecoxib on the phosphorylation status of Akt and extracellular signal regulated kinase (ERK)2 in the COX-2 antisense clone 7D9 with or without doxycycline treatment (2 pg/mL) as indicated. Western blots are representatives of three independent experiments. These data indicate that the mechanism underlying celecoxib-induced apoptotic death in the 7D9 cells remained unaltered after COX-2 depletion. Source Song, X., Lin, H.P., Johnson, A.J., Tseng, P.H., Yang, Y.T., Kulp, S.K., and Chen, C.S. (2002) Cyclooxygenase-2, Player or Spectator in Cyclooxygenase-2 Inhibitor-Induced Apoptosis in Prostate Cancer Cells, j. Natl. Cancer Inst. 94, 585-591 by permission of Oxford University Press.

Familial adenomatous polyposis (FAP) 400 mg twice daily with food, as an adjunct to usual care. (FAP is a hereditary polyposis syndrome with a progression to colorectal cancer. Increased COX-2 protein was found in the polyp specimens from patients with FAP in a dose-dependent manner, early treatment with celecoxib significantly reduces the number of colorectal polyps in patients with FAP) [1]. 

Non-opioid analgesics (NSAIDs, COX-2 inhibitors, APAP), including celecoxib, are part of the World Health Organization s (WHO) analgesic ladder for the treatment of mild to moderate cancer pain. There are no celecoxib dosing guidelines for the treatment of somatic pain associated with cancer. 

Fakih, M.G., Rustum, Y. M. (2009). Does celecoxib have a role in the treatment of patients with colorectal cancer Clinical Colorectal Cancer 8(1), 11-14. 

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