Randomized phase III clinical trial of five different arms of treatment in 332 patients with cancer cachexia.
OBJECTIVE
A phase III, randomized 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), and fatigue-and relevant secondary endpoints: appetite, quality of life, grip strength, Glasgow Prognostic Score (GPS) and proinflammatory cytokines.


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


RESULTS
Analysis of variance showed a significant difference between 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; interleukin (IL)-6 decreased significantly in arm 5 and arm 4; GPS and Eastern Cooperative Oncology Group performance status (ECOG PS) score decreased significantly in arm 5, arm 4, and arm 3. Toxicity was quite negligible, and was comparable between arms.


CONCLUSIONS
The most effective treatment in terms of all three primary efficacy endpoints and the secondary endpoints appetite, IL-6, GPS, and ECOG PS score was the combination regimen that included all selected agents.
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
Elena
E
Massa
Mariele
M
Dessì
Filomena
F
Panzone
Paolo
P
Contu
D019167:Appetite Stimulants / Q000009:adverse effects / Q000627:therapeutic use; D002100:Cachexia / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D002331:Carnitine / Q000009:adverse effects / Q000627:therapeutic use*; D015118:Eicosapentaenoic Acid / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D008525:Medroxyprogesterone / Q000009:adverse effects / Q000627:therapeutic use*; D019290:Megestrol Acetate / Q000009:adverse effects / Q000627:therapeutic use*; D008875:Middle Aged; D009369:Neoplasms / Q000150:complications* / Q000378:metabolism; D013792:Thalidomide / Q000009:adverse effects / Q000627:therapeutic use*; D014803:Vitamin B Complex / Q000009:adverse effects / Q000627:therapeutic use
D019167:Appetite Stimulants; D015850:Interleukin-6; D014803:Vitamin B Complex; D013792:Thalidomide; D015118:Eicosapentaenoic Acid; D008525:Medroxyprogesterone; D002331:Carnitine; D019290:Megestrol Acetate