Cancer cachexia: It's time for more clinical trials

被引:54
作者
Bossola, Maurizio [1 ]
Pacelli, Fabio [1 ]
Tortorelli, Antonio [1 ]
Doglietto, Giovan Battista [1 ]
机构
[1] Univ Cattolica Sacro Cuore, Ist Clin Chirurg, I-00168 Rome, Italy
关键词
cancer cachexia; anorexia; muscle wasting; approved therapy; candidate drugs;
D O I
10.1245/s10434-006-9179-5
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Cancer cachexia (CC) is a multifactorial paraneoplastic syndrome characterized by anorexia, body weight loss, loss of adipose tissue and skeletal muscle, accounting for at least 20% of deaths in neoplastic patients. CC significantly impairs quality of life and response to anti-neoplastic therapies, increasing morbidity and mortality of cancer patients. Muscle wasting is the most important phenotypic feature of CC and the principal cause of function impairment, fatigue and respiratory complications, mainly related to a hyperactivation of muscle proteolytic pathways. Most current therapeutic strategies to counteract CC have proven to be only partially effective. In the last decade, the correction of anorexia, the inhibition of catabolic processes and the stimulation of anabolic pathways in muscle have been attempted pharmacologically with encouraging results in animal models and through preliminary clinical trials. However, data in the clinical setting are still scanty and non definitive. It is time to start prospective, randomized, controlled trials to evaluate which drugs are effective in counteracting the loss of lean of muscle mass and in improving nutritional status and quality of life in patients affected by cancer-related cachexia.
引用
收藏
页码:276 / 285
页数:10
相关论文
共 86 条
[11]  
Brzezinski Amnon, 1997, New England Journal of Medicine, V336, P186
[12]  
CHLEBOWSKI RT, 1986, CANCER, V58, P183, DOI 10.1002/1097-0142(19860701)58:1<183::AID-CNCR2820580131>3.0.CO
[13]  
2-3
[14]   Manipulation of the ubiquitin-proteasome pathway in cachexia:: pentoxifylline suppresses the activation of 20S and 26S proteasomes in muscles from tumor-bearing rats [J].
Combaret, L ;
Rallière, C ;
Taillandier, D ;
Tanaka, K ;
Attaix, D .
MOLECULAR BIOLOGY REPORTS, 1999, 26 (1-2) :95-101
[15]   Anatomy and regulation of the central melanocortin system [J].
Cone, RD .
NATURE NEUROSCIENCE, 2005, 8 (05) :571-578
[16]  
Costelli P, 2005, INT J ONCOL, V26, P1663
[17]   Mechanisms of skeletal muscle depletion in wasting syndromes: role of ATP-ubiquitin-dependent proteolysis [J].
Costelli, P ;
Baccino, FM .
CURRENT OPINION IN CLINICAL NUTRITION AND METABOLIC CARE, 2003, 6 (04) :407-412
[18]   Anticytokine treatment prevents the increase in the activity of ATP-ubiquitin- and Ca2+-dependent proteolytic systems in the muscle of tumour-bearing rats [J].
Costelli, P ;
Bossola, M ;
Muscaritoli, M ;
Grieco, G ;
Bonelli, G ;
Bellantone, R ;
Doglietto, GB ;
Baccino, FM ;
Fanelli, FR .
CYTOKINE, 2002, 19 (01) :1-5
[19]   Activation of Ca2+-dependent proteolysis in skeletal muscle and heart in cancer cachexia [J].
Costelli, P ;
De Tullio, R ;
Baccino, FM ;
Melloni, E .
BRITISH JOURNAL OF CANCER, 2001, 84 (07) :946-950
[20]   A role for anabolic steroids in the rehabilitation of patients with COPD? [J].
Creutzberg, EC ;
Wouters, EFM ;
Mostert, R ;
Pluymers, RJ ;
Schols, AMWJ .
CHEST, 2003, 124 (05) :1733-1742