Abstract 3724: Efficacy and safety of the COX-2 inhibitor celecoxib on patients with cancer cachexia: a phase II non randomized study
Authors: Mantovani Giovanni , Maccio' Antonio , Madeddu Clelia , Panzone Filomena , Serpe Roberto , Massa Elena , Astara Giorgio , Dessiì Mariele , Antoni Giorgia 
Published: February 2011

Abstract
Chronic inflammation is one of the main features of cancer cachexia. Experimental and clinical studies showed that cyclooxygenase (COX)-2 inhibitors, such as celecoxib, may be beneficial in counteracting major symptoms of this devastating syndrome.
We carried out a prospective non randomised 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.
Patient eligibility criteria were: age range of 18-80 years, histologically confirmed tumor of any site at an advanced stage, loss of ≥5% of body weight in the previous 3 months and a life expectancy of ≥4 months. Patients could be receiving concomitant antineoplastic chemotherapy or hormone therapy with palliative intent or supportive care. Exclusion criteria were: women of child-bearing age, positive history of heart disease, history of previous myocardial infarction, unstable angina, coronary revascularization, uncontrolled arrhythmia, congestive heart failure and cerebrovascular accident, previous gastrointestinal inflammatory disease and history of gastrointestinal ulceration, mechanical obstruction to feeding, and medical treatments inducing significant changes of patient metabolism or body weight.
A sample of 24 patients was enrolled from January to December 2008 and all were deemed assessable. The men/women ratio was well balanced (13/11). The mean age was 60.6 years. The most frequent tumor sites were head and neck, lung, and colorectal. Patients were &gt;90% stage IV and the Glasgow Prognostic Score (GPS), an inflammation-based score predictive of patient survival, was high (two) in 50% of them.
Among primary efficacy endpoints, LBM assessed both by BIA (mean increase, +0.6±2.4 kg) and DEXA (mean increase, +0.6±2.7 kg) increased significantly (p&lt;0.0001). The proinflammatory cytokine TNF-α decreased significantly (mean decrease, —6.9±11 pg/ml; p=0.007). Among patients with weight loss associated with high TNF-α levels (16), ten showed an increase of LBM accompanied by a decrease of TNF-α levels, while two showed an increase of LBM without a concomitant decrease of TNF-α.
Among secondary efficacy endpoints, 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 show that the COX-2 selective inhibitor celecoxib is an effective single agent for the treatment of cancer cachexia. Therefore, phase III clinical trials are warranted to test the efficacy and safety of celecoxib.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3724.