Madeddu, C., Dessi, M., Panzone, F., Serpe, R., Antoni, G., Cau, M.C., . . . Mantovani, G. (2011). Randomized phase III clinical trial of a combined treatment with carnitine + celecoxib +/- megestrol acetate for patients with cancer-related anorexia/cachexia syndrome. Clinical Nutrition, 31, 176–182.doi: 10.1016/j.clnu.2011.10.005
To compare the efficacy and safety of a two-drug combination (including nutraceuticals) with carnitine and celecoxib (arm 1) versus megestrol acetate (arm 2) for the treatment of cancer anorexia and cachexia syndrome
No dietary restrictions were placed on participants. Polyphenols (2 tabs, 300 mg/day), lipoic acid (300 mg/day), carbocystine (400 mg/day), vitamin A (30,000 IU/day), and vitamin C (500 mg/day) were administered orally to all patients. Patients were then randomized to treatment arms: arm 1, L-carnitine (4 g/day) + celecoxib, or arm 2, l-carnitine (4 g/day) + celecoxib + megestrol acetate (MA) (320 mg/day). Treatment duration was four months. Measurements were obtained at 4, 8, and 16 weeks. Analysis focused on differences from baseline to 16 weeks. Data were collected from 2009 to 2010. No placebo arm was included for ethical reasons and based on previous research. Planned study duration was four months.
A phase III, randomized, two-group, non-inferiority trial design was used.
Primary endpoints: There was no significant difference (based on t test) between arms for LBM and physical activity. DEXA and CT of L3 significantly increased at 16 weeks from baseline in both arms. BIA did not change in either arm. There were no significant changes in physical activity in either arm. The six-minute walking test improved in both arms, and grip strength did not change significantly in either arm. REE, fatigue, Eastern Cooperative Oncology Group score, and prognostic score decreased significantly in both arms. Body weight did not change significantly in arm 1 but did increase in arm 2 (p = 0.052, which was not significant but on the border and trending). Appetite was reported as improved significantly in both arms (p < 0.05). Fatigue scores were improved significantly in arm 1 after treatment (p = 0.036). Survival measurements did not change and were not significantly different between groups. Two patients reported grade 3 diarrhea.
No significant differences were found in patients based on the intervention arm.
A multimodal approach may help to improve anorexia and cachexia in patients with cancer. More work focused on patient-reported outcomes, safety, and adherence is needed. Specific description of how appetite is assessed should be included in studies reporting this outcome measure.