Phase II nonrandomized study of the efficacy and safety of COX-2 inhibitor celecoxib on patients with cancer cachexia.
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-alpha 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.
Mantovani
Giovanni
G
Department of Medical Oncology, University of Cagliari, Cagliari, Italy. mantovan@medicina.unica.it
Macciò
Antonio
A
Madeddu
Clelia
C
Serpe
Roberto
R
Antoni
Giorgia
G
Massa
Elena
E
Dessì
Mariele
M
Panzone
Filomena
F
D000368:Aged; D002100:Cachexia / Q000188:drug therapy* / Q000209:etiology; D000068579:Celecoxib; D052246:Cyclooxygenase 2 Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008875:Middle Aged; D009369:Neoplasms / Q000150:complications*; D011720:Pyrazoles / Q000009:adverse effects* / Q000627:therapeutic use*; D013449:Sulfonamides / Q000009:adverse effects* / Q000627:therapeutic use*
D052246:Cyclooxygenase 2 Inhibitors; D011720:Pyrazoles; D013449:Sulfonamides; D000068579:Celecoxib