Phase II nonrandomized study of the efficacy and safety of COX-2 inhibitor celecoxib on patients with cancer cachexia
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Chronic inflammation is one of the main features of cancer cachexia. Experimental and clinical studies showed that cyclooxygenase-2 inhibitors, such as celecoxib, may be beneficial in counteracting major symptoms of this devastating syndrome. We carried out a prospective phase II clinical trial to test the safety and effectiveness of an intervention with the COX-2 inhibitor celecoxib (300 mg/day for 4 months) on key variables of cachexia (lean body mass, resting energy expenditure, serum levels of proinflammatory cytokines, and fatigue) in patients with advanced cancer at different sites. A sample of 24 patients was enrolled from January to December 2008 and all were deemed assessable. A significant increase of lean body mass and a significant decrease of TNF-α were observed. Moreover, an improvement of grip strength, quality of life, performance status, and Glasgow prognostic score was shown. There were no grade 3/4 toxicities. Patient compliance was very good; no patient had to reduce the celecoxib dosage nor interrupt treatment. Our results showed that the COX-2 selective inhibitor celecoxib is an effective single agent for the treatment of cancer cachexia. Although the treatment of cancer cachexia, a multifactorial syndrome, is more likely to yield success with a multitargeted approach; in the present study, we were able to show that a treatment, such as celecoxib, addressing a single target, albeit very important as chronic inflammation, could have positive effects. Therefore, phase III clinical trials are warranted to test the efficacy and safety of celecoxib.
KeywordsCancer cachexia Chronic inflammation COX-2 inhibitors Celecoxib Lean body mass, resting energy expenditure Proinflammatory cytokines Fatigue
The authors take full responsibility for the content of the paper but thank Ms. Anna Rita Succa for her assistance in editing the article.
The authors have no financial or personal relationships with other people or organizations that could inappropriately influence their work.
- 5.Nelson K, Walsh D (1991) Management of the anorexia/cachexia syndrome. Cancer Bull 43:403–406Google Scholar
- 10.Busbridge J, Dascombe MJ, Hoopkins S (1989) Acute central effects of interleukin-6 on body temperature, thermogenesis and food intake in the rat. Proc Nutr Soc 38:48AGoogle Scholar
- 22.Saito H, Inagaki Y, Tsunenari T, Ura M, Mizuno H, Fujimoto-Ouchi K, Onuma E, Sato K, Ogata E, Yamada-Okabe H (2007) Involvement of cyclooxygenase-2 in the tumor site-dependent production of parathyroid hormone-related protein in colon 26 carcinoma. Cancer Sci 98:1563–1569CrossRefPubMedGoogle Scholar
- 23.Diament MJ, Peluffo GD, Stillitani I, Cerchietti LC, Navigante A, Ranuncolo SM, Klein SM (2006) Inhibition of tumor progression and paraneoplastic syndrome development in a murine lung adenocarcinoma by medroxyprogesterone acetate and indomethacin. Cancer Invest 24:126–131CrossRefPubMedGoogle Scholar
- 25.Mantovani G, Maccio A, Madeddu C, Gramignano G, Lusso MR, Serpe R, Massa E, Astara G, Deiana L (2006) A phase II study with antioxidants, both in the diet and supplemented, pharmaconutritional support, progestagen, and anti-cyclooxygenase-2 showing efficacy and safety in patients with cancer-related anorexia/cachexia and oxidative stress. Cancer Epidemiol Biomarkers Prev 15:1030–1034CrossRefPubMedGoogle Scholar
- 26.Cerchietti LC, Navigante AH, Peluffo GD, Diament MJ, Stillitani I, Klein SA, Cabalar ME (2004) Effects of celecoxib, medroxyprogesterone, and dietary intervention on systemic syndromes in patients with advanced lung adenocarcinoma: a pilot study. J Pain Symptom Manage 27:85–95CrossRefPubMedGoogle Scholar
- 32.NIH guide. Cachexia: research into biobehaviorial management and quality of life. June 11, 2001.Google Scholar
- 33.Therasse P, Arbuck SG, Eisenhauer EA, Wanders J, Kaplan RS, Rubinstein L, Verweij J, Van Glabbeke M, van Oosterom AT, Christian MC et al (2000) New guidelines to evaluate the response to treatment in solid tumors. European organization for research and treatment of cancer, national cancer institute of the United States, national cancer institute of Canada. J Natl Cancer Inst 92:205–216CrossRefPubMedGoogle Scholar
- 34.National Cancer Institute-Cancer Therapy Evaluation Program: common terminology criteria for adverse events v3.0 (CTCAE), August 9, 2006Google Scholar