The Janus-Faced Role of Antioxidants in Cancer Cachexia: New Insights on the Established Concepts

Table 2

List of main clinical intervention studies with antioxidants on cachectic patients. One open nonrandomized trial (NRT) shows that, at the baseline, cachectic patients present higher ROS levels and lower GPx activity in blood samples comparing to healthy control subjects. Phases II and III studies show that a combination of antioxidants and other agents, including appetite stimulants (megestrol acetate, MA), anti-inflammatory COX-2 inhibitors (celecoxib, CXB), omega-3 rich fatty acid (eicosapentaenoic acid, EPA), enhancers of lipid β-oxidation (L-carnitine, L-CAR), and immune-modulatory agents (thalidomide, TMD), decreases the levels of ROS in the blood, augment the enzymatic antioxidant activity of GPx, and improve performance status (PS) in cancer cachectic patients. Data are presented in the table as mean values that reached statistical significant difference (). No statistically different values are replaced with NSD.

References	Cachectic patient population	Type of study	OS biomarkers (baseline); Cachectic versus healthy control		Treatment		⁢Clinical outcomes (baseline versus treatment)
			ROS (FORT U)	GPx (U/L)	AO types	Other agents	PS: ECOG score	ROS (FORT U)	GPx (U/L)
Maccio et al. 2012 [12]	Ovary, endometrium, and cervix cancer: 104	R-phase III, 4 mo	—	—	ALA and CS	L-CAR + CXB + MA	1.75 versus 1.12	528 versus 444	6007 versus 7458
Madeddu et al. 2012 [13]	Including H&N, lung, and colorectal: 60	R-phase III, 4 mo	—	—	ALA, CS, PLP, and Vit A, C & E	L-CAR + CXB + MA	1.7 versus 1.4	—	—
Mantovani et al. 2010 [14]	Including breast, pancreas, and colon: 332	R-phase III, 4 mo	—	—	ALA, CS, PLP, and Vit A, C & E	MA + EPA + TMD + L-CAR	2 versus 1.5	NSD	NSD
Mantovani et al. 2006 [15]	Including breast, lung, and stomach: 39	NR-phase II, 4 mo	—	—	ALA, CS, PLP, and Vit A, C & E	EPA + MA + CXB	—	468.5 versus 436.6	NSD
Mantovani et al. 2003 [16]	Including H&N, colon, and lung: 56	NRT, 10 d	403.4 versus 172	6770.6 versus 10813	ALA, CS, NAC, and Vit A, C & E	—	Correlation with OS markers	403.45 versus 345.9	6770.6 versus 9263.7

α-Lipoic acid (ALA, 600 mg/day) and carbocysteine (CS: 2.7 g/day); N-acetylcysteine (NAC: 1800 mg/day), ALA (200 mg/day), CS (2.7 g/day), Vit A (30000 IU/day), Vit C (500 mg/day), and Vit E (70 mg/day); and polyphenols (PLP: 300–400 mg/day), ALA (300 mg/day), CS (2.7 g/day), Vit A (30000 IU/day), Vit C (500 mg/day), and Vit E (400 mg/day). Cachectic patients with high ROS levels and low GPx activity exhibited poor performance status. H&N: head and neck cancer.