Daneryd P, Svanberg E, Körner U, Lindholm E, Sandström R, Brevinge H, Pettersson C, Bosaeus I, Lundholm K
Department of Surgery and Clinical Nutrition, Sahlgrenska University Hospital, Göteborg University, Sweden.
Cancer Res. 1998 Dec 1;58(23):5374-9.
This study was aimed at evaluating whether anemia could be prevented in unselected weight-losing cancer patients on anti-inflammatory treatment by early and prophylactic treatment with recombinant human erythropoietin (rhEPO) and whether such a benefit could be translated into improved physical function and metabolic efficiency. One hundred eight cancer patients who experienced progressive cachexia due to solid, mainly gastrointestinal tumors were randomized to receive twice daily a cyclo-oxygenase inhibitor (controls; indomethacin, 50 mg twice a day) or indomethacin and erythropoietin, provided on individual basis to prevent development of progressive anemia (study patients; indomethacin, 50 mg twice a day plus rhEPO; range, 12,000-30,000 units per week). All patients were treated and followed up until death or to preterminal stage. Biochemical tests (blood, liver, kidney, and thyroid), nutritional state assessment (food intake and body composition), and exercise testing with simultaneous measurements of respiratory gas exchanges before and during exercise were performed before institution of treatments and then at regular intervals during the treatment period (2-30 months after start). Study and control patients did not differ in survival. rhEPO prevented development of anemia during the entire observation period. This was associated with a significantly more preserved maximum exercise capacity in study patients compared to control patients during the follow-up period (101 +/- 10 versus 66 +/- 6 W; P < 0.0001), based on more effective ventilation and whole-body respiratory gas exchanges. These improvements were also evident when exercise performance was normalized to lean body mass, an indirect measure of the skeletal muscle mass. The metabolic efficiency, expressed as oxygen uptake per watt produced, was also significantly preserved in rhEPO-treated patients compared to controls (14.1 +/- 1.1 versus 16.3 +/- 0.9 ml O2/W, P < 0.05). Our results demonstrate that institution of early and prophylactic rhEPO treatment to patients with progressive cancer prevents development of tumor-induced anemia. This achievement was associated with a better preserved exercise capacity, which is explained in part by improved whole-body metabolic and energy efficiency during work load.
本研究旨在评估对于未筛选的正在接受抗炎治疗的体重减轻的癌症患者，通过早期预防性使用重组人促红细胞生成素（rhEPO）治疗是否能够预防贫血，以及这种益处是否能转化为身体功能和代谢效率的改善。108例因实体瘤（主要是胃肠道肿瘤）导致进行性恶病质的癌症患者被随机分组，一组每日两次接受环氧化酶抑制剂治疗（对照组；吲哚美辛，每日两次，每次50mg），另一组接受吲哚美辛和促红细胞生成素治疗，根据个体情况给予促红细胞生成素以预防进行性贫血的发生（研究组患者；吲哚美辛，每日两次，每次50mg加rhEPO；剂量范围为每周12,000 - 30,000单位）。所有患者均接受治疗并随访直至死亡或进入终末期。在开始治疗前以及治疗期间（开始后2 - 30个月）定期进行生化检查（血液、肝脏、肾脏和甲状腺）、营养状态评估（食物摄入量和身体成分）以及运动测试，并同时测量运动前后的呼吸气体交换情况。研究组和对照组患者的生存率无差异。rhEPO在整个观察期内预防了贫血的发生。基于更有效的通气和全身呼吸气体交换，与对照组患者相比，研究组患者在随访期间最大运动能力得到了显著更好的保留（101±10对66±6W；P < 0.0001）。当将运动表现按照去脂体重（骨骼肌质量的间接测量指标）进行标准化时，这些改善也很明显。与对照组相比，rhEPO治疗的患者以每产生一瓦功率所摄取的氧量表示的代谢效率也得到了显著保留（14.1±1.1对16.3±0.9ml O2/W，P < 0.05）。我们的结果表明，对进行性癌症患者进行早期预防性rhEPO治疗可预防肿瘤诱导的贫血。这一成果与更好地保留运动能力相关，部分原因是在工作负荷期间全身代谢和能量效率得到了改善。
