Randomized phase III clinical trial of two different arms of a combined treatment with carnitine plus celecoxib with or without megestrol acetate for patients with cancer-related anorexia/cachexia syndrome (CACS).

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e19733 Background: Cancer-related anorexia/cachexia syndrome (CACS) is a multifactorial syndrome characterized by loss of lean body mass (LBM), metabolic alterations, chronic inflammation and fatigue. Methods: In October 2009 we started a phase III randomised study to establish which was the most effective and safest treatment to improve the “key” variables of CACS: increase of LBM, decrease of resting energy expenditure (REE), improvement of fatigue (MFSI-SF) and physical activity (ArmBand). As secondary endpoints we evaluated: grip strength, six minute walk test (6MW), appetite, serum levels of IL-6 and TNF-a, EORTC-QLQ-C30, Glasgow Prognostic Score (GPS), ECOG PS. All patients received as basic oral treatment poliphenols + alpha lipoic acid + carbocysteine + Vitamins A,C,E and were then randomly assigned to: L-carnitine 4 g/d + Celecoxib 300 mg/d (Arm 1) or the same treatment + megestrol acetate (MA) 320 mg/d (Arm 2). Treatment duration: 4 months. The planned sample size was 70 patients for each arm. An interim analysis (intent-to treat) was planned. Results: Sixty cachectic patients (mean age 65.2 ± 8.7 years) with tumors at different sites were enrolled and 57 were evaluable (3 died early due to disease progression). Analysis of changes from baseline showed that LBM assessed by DEXA as well as by L3-CT improved in both arms. Fatigue improved significantly in both arms. REE and physical activity did not show significant changes. As for secondary endpoints, the 6MW test, appetite, GPS and ECOG PS improved significantly. The comparison between the 2 arms by ANOVA test did not show a significant difference. Toxicity was substantially negligible and comparable between arms (1 grade 3 diarrhea in arm 1 and 2, which led to the withdrawal of carnitine for 2 weeks). Conclusions: Both arms showed to be effective as for primary efficacy endpoints (improvement of LBM and fatigue) and some important secondary endpoints. The results of the present trial confirm the efficacy of a combined approach for the treatment of CACS: arm 1, without MA, could be the treatment of choice as it was effective and easier to administer. The trial is ongoing.