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.
Department of Medical Oncology, University of Cagliari, Cagliari, Italy. mantovan@medicina.unica.it
Giovanni
G
Mantovani
Antonio
A
Macciò
Clelia
C
Madeddu
Roberto
R
Serpe
Giorgia
G
Antoni
Elena
E
Massa
Mariele
M
Dessì
Filomena
F
Panzone
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