A combined treatment approach for cachexia and cancer-related anemia in advanced cancer patients: A randomized placebo-controlled trial.

Abstract

189 Background: Cancer progression is characterized by specific energy metabolism alterations and by symptoms including fatigue, anorexia, nausea, depression, which results in cachexia syndrome and compromised quality of life (QL). This condition is often associated to anemia (cancer-related anemia, CRA), which negatively impacts patient QL and disease outcome. Methods: Adult advanced cancer patients with cachexia (i.e., weight loss > 5% in the previous 6 months) and CRA were randomly assigned (1:1 by computer generated list) to receive 3 months of a combined approach consisting of celecoxib (200 mg/day), L-carnitine (2 g/day), curcumin (Meriva) (4 g/day) and lactoferrin (200 mg/day) or placebo. The rationale for selecting these agents was: L-carnitine for modulating cell energy metabolism; celecoxib for counteracting inflammation, which is a key feature of cachexia; curcumin for its antiinflammatory and antioxidant action, without disregarding its action on the NF-kB and JAK-STAT pathway and the related synthesis of proinflammatory cytokines; lactoferrin for its ability to regulate iron metabolism in anemic cancer patients. Primary endpoints were improvement of lean body mass (LBM), appetite, fatigue and anemia. Additionally, we assessed the impact of treatment on the main metabolic/inflammatory and iron metabolism parameters: C-reactive protein (CRP), interleukin (IL)-6, tumor necrosis factor (TNF)-α, leptin, reactive oxygen species (ROS), glutathione peroxidase, serum iron, ferritin, hepcidin and erythropoietin (EPO). Results: From January 2013 to March 2014, 66 patients have been enrolled. The combination arm was more effective than placebo arm in improving body weight, LBM, appetite, fatigue, and anemia. Among secondary parameters IL-6, TNF-α, CRP, ROS, ferritin, hepcidin and EPO decreased, while leptin increased significantly in the combination arm. No significant changes were observed in the placebo arm. Conclusions: To date a standard effective treatment of cancer cachexia is lacking. Our combined multitargeted approach was able to improve the nutritional and immunometabolic alterations of cachexia, ameliorate patient QL and correct CRA.

COVID-19 and cytokine storm syndrome: can what we know about interleukin-6 in ovarian cancer be applied?

“…Thus, in the tolerance phase, targeting the symptoms consequent to chronic inflammation, such as thrombosis, anemia, anorexia, weight loss, muscle wasting is fundamental for an effective treatment strategy. Therefore, treatment with immunomodulatory and immunosuppressive drugs, such as glucocorticoids and low molecular weight heparin, to prevent or treat the associated thrombotic events, as well as administration of supportive drugs, such as antioxidants and lactoferrin, which help to restore the defective function of the adaptive specific immunity and modulate the altered iron metabolism, as observed in patients with advanced ovarian cancer [ 29 , 139 ], may prove beneficial even in the absence of specific antiviral treatments. In a randomized clinical trial [ 140 ] we have demonstrated in patients with advanced cancer, primarily ovarian cancer, with chemotherapy-related anemia, that lactoferrin mobilized iron storage thereby reducing ferritin levels and increasing iron availability for erythropoiesis and heme proteins synthesis, such as myoglobin and cytochrome chain.…”

Dietary Supplements in People with Metastatic Cancer Who Are Experiencing Malnutrition, Cachexia, Sarcopenia, and Frailty: A Scoping Review

“…Of the full text peer-reviewed manuscripts, the majority reported on randomized controlled trials (RCTs) (n = 18) [34][35][36][37][38][39][40][41][42][43][44][45][46][47][48][49][50][51], followed by quasi-experimental trials (n = 15) [52][53][54][55][56][57][58][59][60][61][62][63][64][65][66], retrospective cohort observational studies (n = 2) [67,68], and case studies (n = 3) [69][70][71]. Conference abstracts reported on RCTs (n = 3) [72][73][74], quasi-experimental trials (n = 4) [75][76][77][78], and a case study (n = 1) [79]. The two clinical trial registrations consisted of one RCT [80], which was terminated as sample size could not be reached, and one quasi-experimental trial ...…”

“…Minerals included were calcium (n = 2) [62,64], iron (n = 2) [68,79], and selenium (n = 1) [75]. Antioxidants (other than vitamins and minerals) included carbocysteine (n = 4) [42,44,54,74], lipoic acid (n = 4) [42,44,54,74], quercetin (n = 2) [44,54], curcumin (n = 2) [73,77], and lycopene (n = 1) [66].…”

“…Curcumin was investigated as the sole dietary supplement in a quasi-experimental trial in doses of 2 g daily (equivalent to 400 mg daily of active curcuminoids extract) [77]. In an RCT, curcumin was administered as part of a combined treatment including other dietary supplements (carnitine and lactoferrin) at a dose of 4 g daily [73]. Lycopene was investigated in only one study (quasi-experimental trial), where it was given at a dose of 30 mg daily in people receiving concomitant docetaxel therapy [66].…”

Therapeutic strategies against cancer cachexia

“…95 A combined multitargeted approach in a randomized placebo-controlled trial, using celecoxib, L-carnitine, curcumin and lactoferrin, was able to improve the nutritional and immunometabolic alterations of cachexia, ameliorate the patient quality of life and correct cancer-related anemia. 96 Practical (individual reports) multimodal care programs for cancer cachexia have been recently published. 97 Another critical factor that may positively contribute to cancer cachexia treatment is a proper staging of the cachectic condition in cancer patients.…”