Randomised phase III clinical trial of 5 different arms of treatment on 332 patients with cancer cachexia.
OBJECTIVE
A phase III randomised study was carried out to establish the most effective and safest treatment to improve the primary endpoints of cancer cachexia: lean body mass (LBM), resting energy expenditure (REE), fatigue; and relevant secondary endpoints: appetite, quality of life, grip strength, Glasgow Prognostic Score (GPS) and proinflammatory cytokines.


METHODS
Three hundred and thirty-two assessable patients with cancer-related anorexia/cachexia syndrome (CACS) were randomly assigned to one of five arms of treatment: 1--medroxyprogesterone 500 mg/d or megestrol acetate 320 mg/d; 2--oral supplementation with eicosapentaenoic acid (EPA); 3--L-carnitine 4 g/d; 4--thalidomide 200 mg/d; 5--a combination of the above. Treatment duration: 4 months.


RESULTS
Analysis of variance showed a significant difference between the treatment arms. A post hoc analysis showed the superiority of arm 5 over the others for all primary endpoints. An analysis of changes from baseline showed that LBM (by dual-energy X-ray absorptiometry and by L3 computed tomography) significantly increased in arm 5. REE decreased significantly and fatigue improved significantly in arm 5. Appetite increased significantly in arm 5. IL-6 decreased significantly in arm 5 and 4. GPS significantly decreased in arms 5, 4 and 3. Total daily physical activity showed that total energy and active energy expenditure increased significantly in arm 5. Eastern Cooperative Oncology group-Performance Status (ECOG-PS) significantly decreased in arms 5, 4 and 3. Toxicity was substantially negligible, comparable between treatment arms.


CONCLUSIONS
The most effective treatment for all three primary efficacy endpoints as well as secondary endpoints appetite, IL-6, GPS and ECOG PS was the combination regimen that included all selected agents.
Mantovani
G
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Department of Medical Oncology, Schoool of Medicine, University of Cagliari, Italy. mantovan@medicina.unica.it
D000368:Aged; D001823:Body Composition / Q000187:drug effects; D002100:Cachexia / Q000188:drug therapy* / Q000209:etiology*; D002331:Carnitine / Q000627:therapeutic use*; D003278:Contraceptives, Oral, Hormonal / Q000627:therapeutic use*; D015118:Eicosapentaenoic Acid / Q000627:therapeutic use*; D023381:Endpoint Determination; D004734:Energy Metabolism; D005260:Female; D006801:Humans; D008297:Male; D008525:Medroxyprogesterone / Q000627:therapeutic use*; D008535:Megestrol / Q000627:therapeutic use*; D008875:Middle Aged; D009043:Motor Activity; D009369:Neoplasms / Q000150:complications*; D011379:Prognosis; D013792:Thalidomide / Q000627:therapeutic use*
D003278:Contraceptives, Oral, Hormonal; D013792:Thalidomide; D015118:Eicosapentaenoic Acid; D008535:Megestrol; D008525:Medroxyprogesterone; D002331:Carnitine