Randomized phase III clinical trial of five different arms of treatment for patients with cancer cachexia: interim results.
OBJECTIVE
In April 2005 a phase III randomized study was started to establish which was the most effective and safest treatment of cancer-related anorexia/cachexia syndrome and oxidative stress in improving identified primary endpoints: increase of lean body mass, decrease of resting energy expenditure (REE), increase of total daily physical activity, decrease of interleukin-6 and tumor necrosis factor-alpha, and improvement of fatigue assessed by the Multidimensional Fatigue Symptom Inventory-Short Form (MFSI-SF).


METHODS
All patients were given as basic treatment polyphenols plus antioxidant agents alpha-lipoic acid, carbocysteine, and vitamins A, C, and E, all orally. Patients were then randomized to one of the following five arms: 1) medroxyprogesterone acetate/megestrol acetate; 2) pharmacologic nutritional support containing eicosapentaenoic acid; 3) L-carnitine; 4) thalidomide; or 5) medroxyprogesterone acetate/megestrol acetate plus pharmacologic nutritional support plus L-carnitine plus thalidomide. Treatment duration was 4 mo. The sample comprised 475 patients.


RESULTS
By January 2007, 125 patients, well balanced for all clinical characteristics, were included. No severe side effects were observed. As for efficacy, an interim analysis on 125 patients showed an improvement of at least one primary endpoint in arms 3, 4, and 5, whereas arm 2 showed a significant worsening of lean body mass, REE, and MFSI-SF. Analysis of variance comparing the change of primary endpoints between arms showed a significant improvement of REE in favor of arm 5 versus arm 2 and a significant improvement of MFSI-SF in favor of arms 1, 3, and 5 versus arm 2. A significant inferiority of arm 2 versus arms 3, 4, and 5 for the primary endpoints lean body mass, REE, and MFSI-SF was observed on the basis of t test for changes.


CONCLUSIONS
The interim results obtained thus far seem to suggest that the most effective treatment for cancer-related anorexia/cachexia syndrome and oxidative stress should be a combination regimen. The study is still in progress and the final results should confirm these data.
Mantovani
Giovanni
G
Department of Medical Oncology, University of Cagliari, Cagliari, Italy. mantovan@pacs.unica.it
Macciò
Antonio
A
Madeddu
Clelia
C
Gramignano
Giulia
G
Serpe
Roberto
R
Massa
Elena
E
Dessì
Mariele
M
Tanca
Francesca Maria
FM
Sanna
Eleonora
E
Deiana
Laura
L
Panzone
Filomena
F
Contu
Paolo
P
Floris
Carlo
C
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology; D000975:Antioxidants / Q000008:administration & dosage*; D019167:Appetite Stimulants / Q000494:pharmacology; D001205:Ascorbic Acid / Q000008:administration & dosage; D001481:Basal Metabolism / Q000187:drug effects / Q000502:physiology; D002100:Cachexia / Q000209:etiology / Q000628:therapy*; D002331:Carnitine / Q000494:pharmacology; D019587:Dietary Supplements; D015444:Exercise / Q000502:physiology; D005221:Fatigue / Q000517:prevention & control; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis; D008297:Male; D017258:Medroxyprogesterone Acetate / Q000494:pharmacology; D019290:Megestrol Acetate / Q000494:pharmacology; D008875:Middle Aged; D009124:Muscle Proteins / Q000096:biosynthesis; D009369:Neoplasms / Q000150:complications; D018529:Nutritional Support / Q000379:methods*; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D014801:Vitamin A / Q000008:administration & dosage; D014810:Vitamin E / Q000008:administration & dosage
D018931:Antineoplastic Agents, Hormonal; D000975:Antioxidants; D019167:Appetite Stimulants; D015850:Interleukin-6; D009124:Muscle Proteins; D014409:Tumor Necrosis Factor-alpha; D014801:Vitamin A; D014810:Vitamin E; D017258:Medroxyprogesterone Acetate; D001205:Ascorbic Acid; D002331:Carnitine; D019290:Megestrol Acetate