epoetin-alfa and Cachexia

A controlled clinical trial was conducted to evaluate the use of epoetin alfa in cachectic patients with solid tumors who were not receiving chemotherapy to determine if increasing hemoglobin (Hb) resulted in increased exercise capacity, metabolism, and energy efficiency during a maximum work load. The randomized, prospective study included 108 patients who received oral indomethacin 50 mg twice daily (n = 58; control group), or oral indomethacin 50 mg twice daily with epoetin alfa 4,000 to 10,000 IU by subcutaneous injection 3 times weekly (n = 50; study group). Patients randomized to the study group received epoetin alfa only when Hb decreased below 12.8 g/dL for men and 12.0 g/dL for women. Mean Hb levels in the study group were significantly (P <.0001) improved overall compared with the control group, with significant differences seen between groups after 2 to 4 months (P <.003), 6 to 8 months (P <.01), and 10 to 30 months (P <.01). Mean inflammatory variables including serum albumin, erythrocyte sedimentation rate, and C-reactive protein were significantly (P <.02) changed in the study group compared with the control group (ie, the control group had more inflammation). Significantly lower mean body weight (P <.05) and resting energy expenditure (P <.007) were recorded for patients in the control group versus the study group. The study group showed significantly greater mean exercise capacity (P <.0001), mean oxygen uptake (P <.01), mean CO(2) production (P <.009), and respiration (P <.03). These results demonstrate that early use of epoetin alfa prevents anemia in patients with progressive cancer who are not receiving chemotherapy. Normalization of Hb levels resulted in improved whole-body metabolism and energy efficiency, which is associated with greater exercise capacity and better daily quality of life.

Topics: Aged; Anemia; Anti-Inflammatory Agents, Non-Steroidal; Cachexia; Cyclooxygenase Inhibitors; Energy Metabolism; Epoetin Alfa; Erythropoietin; Female; Hematinics; Hemoglobins; Humans; Indomethacin; Male; Middle Aged; Neoplasms; Physical Exertion; Prospective Studies; Quality of Life; Recombinant Proteins

Cancer cachexia is a syndrome characterized by loss of skeletal muscle mass, inflammation, anorexia and anemia, contributing to patient fatigue and reduced quality of life. In addition to nutritional approaches, exercise training (EX) has been proposed as a suitable tool to manage cachexia. In the present work the effect of mild exercise training, coupled to erythropoietin (EPO) administration to prevent anemia, has been tested in tumor-bearing mice. In the C26 hosts, acute exercise does not prevent and even worsens muscle wasting. Such pattern is prevented by EPO co-administration or by the adoption of a chronic exercise protocol. EX and EPO co-treatment spares oxidative myofibers from atrophy and counteracts the oxidative to glycolytic shift, inducing PGC-1α. LLC hosts are responsive to exercise and their treatment with the EX-EPO combination prevents the loss of muscle strength and the onset of mitochondrial ultrastructural alterations, while increases muscle oxidative capacity and intracellular ATP content, likely depending on PGC-1α induction and mitophagy promotion. Consistently, muscle-specific PGC-1α overexpression prevents LLC-induced muscle atrophy and Atrogin-1 hyperexpression. Overall, the present data suggest that low intensisty exercise can be an effective tool to be included in combined therapeutic approaches against cancer cachexia, provided that anemia is coincidently treated in order to enhance the beneficial action of exercise.

Topics: Anemia; Animals; Blotting, Western; Cachexia; Disease Models, Animal; Epoetin Alfa; Exercise Therapy; Female; Hematinics; Male; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Transgenic; Microscopy, Electron, Transmission; Muscle, Skeletal; Muscular Atrophy; Neoplasms, Experimental; Physical Conditioning, Animal; Real-Time Polymerase Chain Reaction

Within hypoxic tumor regions anaerobic dissimilation of glucose is the sole source of energy generation. It yields only 5% of the ATP that is normally gained by means of oxidative glucose catabolism. The increased need for glucose may aggravate cancer cachexia. We investigated the impact of recombinant human erythropoietin (RhEPO) and increased inspiratory oxygen concentrations on weight loss in tumor-bearing mice.. Fragments of the murine C26-B adenocarcinoma were implanted in 60 BALB/c-mice. The mice were divided into four groups and assigned to: (A) no treatment; (B) RhEPO- administration (25 IU daily from day 1-11, three times per week from day 12); (C) RhEPO and 25% oxygen; and (D) RhEPO and 35% oxygen. Three control groups of four healthy mice each received the same treatment as groups A, B, and D, respectively. Hematocrit and hemoglobin levels, tumor volume, and body weight were monitored. At day 17 the experiment was terminated and the serum lactate concentration was measured. The tumors were excised and weighed and, for each mouse, the percentage weight loss was calculated. The impact of tumor weight and the treatments on lactate concentration and weight loss was evaluated.. Significant positive correlations were found between tumor weight and lactate concentration and between tumor weight and percentage weight loss. In the mice with the largest tumors, RhEPO displayed a significant weight loss-reducing effect, and a significant negative correlation was found between hemoglobin concentration and weight loss. An oxygen-rich environment did not appear to influence weight loss.. Anaerobic glycolysis in a growing C26-B tumor is related to weight loss. RhEPO administration results in a reduction of the percentage weight loss; this effect is probably mediated by an increased hemoglobin concentration.

Topics: Adenocarcinoma; Animals; Cachexia; Disease Models, Animal; Epoetin Alfa; Erythropoietin; Glycolysis; Hematocrit; Hemoglobins; Inhalation; Mice; Mice, Inbred BALB C; Oxygen; Recombinant Proteins; Weight Loss