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本帖最后由 老马 于 2014-11-24 16:44 编辑 : s. A1 ^' A4 n+ n" h; Q
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恶性肿瘤患者食欲不佳主要与恶性肿瘤的生长、肿瘤破坏过程中毒素的释放、手术、放化疗和靶向药的副作用及心理因素等有关。
4 t9 J* k' ?9 {- U4 N5 P恶性肿瘤病人能量、碳水化合物、脂肪及蛋白质代谢均有很大程度的改变。能量消耗增加和低效率的能量利用常被认为是荷瘤机体营养不良的原因。机体的基础代谢率与疾病进程及营养物质摄入成反比例。恶性肿瘤病人的乳酸循环活性增加，在这一无用的循环中，葡萄糖被转化为乳酸，继而又在肝细胞内转化为葡萄糖，这种低效的循环同时还是一个耗能过程，病人的乳酸循环活性越高，能量消耗越大，体重减少也越明显。恶性肿瘤机体对胰岛素的敏感性往往受损，葡萄糖耐受性下降，病人肌肉和肝脏中内源性糖原贮备较少，稍有饥饿即可耗尽，而神经细胞和红细胞对葡萄糖的利用仍在进行，机体分解蛋白质进行糖异生。在非癌症病人、肌肉蛋白质分解逐渐由脂肪代谢所代替，脂肪酸转化为酮体给机体供能，从而节省肌肉蛋白。而在癌症病人，机体丧失了为应激状态下所设置的保存体蛋白的正常机制，结果葡萄糖产生增加，同时蛋白质分解也增加，肌肉蛋白质合成减少，机体氮丢失，血清氨基酸谱异常。30%~100%进展期恶性肿瘤病人呈负氮平衡。" V" D& P2 o; ?' d2 h6 M, \/ j3 M- u! L
一、改变饮食习惯1 d% e3 U r; q2 U* x
1、少食多餐，提供高能量、高蛋白质饮食或营养补充品。- h9 ?! k' S8 e) U. w7 K' @/ J
2、更换食谱，尝试用各种温和的调味料，经常变化烹饪方式与形态，增强色香味。$ Q5 c- X# z( W# Q+ [& r0 E2 V5 a
3、餐前做适量的运动（比如散步）或食用开胃食物。! s# D& ^5 A) g
4、进餐时应保持愉快的心情，可以观看喜欢的电视节目或者播放轻音乐。
) k- `2 S, ~* ]5、用餐时先食用固体食物，再饮用液体汤汁或饮料。( s& S, i% B7 C4 E
6、若感觉疲劳，应休息片刻，待体力恢复后再进食。尽量少摄入油腻食物。4 M3 ^7 \" }$ A, f: f8 z
7、每天补充适量的维生素、矿物质、水分。
* f1 p Y+ a0 T) b0 }* j& v8、使用大的碗碟盛食物，显得份量不多。$ v/ g+ |! f. _- V+ n, {
二、常用药物: } N( p( z& g) f* U
1、抗恶心药物：胃复安(metoclopramide)8 w- D$ o. y4 \
2、促进食欲药物：
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2 ?7 }0 d. a V甲地孕酮（Megestrol acetate）：160mg每天，一天一次口服，7-28天。（甲地孕酮的剂量从160mg每天增加到320~480mg每天，体重增加更多，而食欲改善无区别。更高的剂量，无更多的益处。）
& m: t/ @+ E# F6 O4 h4 j$ ]地塞米松（dexamethasone）：每天2-4mg，一天分二次口服。
1 g- J$ T" }; m) x! t大麻提取物：四氢大麻酚（Dronabinol），四氢大麻醇（cannabinoid）等
3 J, H6 T/ E- g! _# h3 X3、助消化药物：多酶片4 A" K# m n6 b7 ~' N5 q* T
4、促胃肠动力药：吗丁啉（多潘立酮）(domperidone)、西沙比利(cisapride、prepulsid,普瑞博思)、莫沙比利（Mosapride ,贝络纳，加斯清）、替加色罗(Tegaserod，泽马可)。2 P' m+ z6 m. j5 }4 c8 E
5、微生态制剂：培菲康(Bifico, 双歧三联活菌胶囊). h; p) u2 C0 o2 h j) M, z7 g
6、抗抑郁药：米尔塔扎平（mirtazapine）、百忧解（Prozac）9 _# p' S& d! i, {
三、推荐的保健品/ B0 w+ O! A5 X, D8 F. M6 `
1、雀巢的速愈素、雅培的保康速和安素
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3、乳铁蛋白
% e2 Z' r. O" ]- ]! r四、营养支持与肿瘤生长的关系( e ~. v6 z" m3 k: T& ~( i5 O
对肿瘤病人进行营养支持时，人们可能担心营养支持可能会使肿瘤受益。动物实验表明，营养支持在改善荷瘤宿主营养状况的同时，对肿瘤细胞动力学也产生影响，可导致肿瘤组织蛋白合成增加，肿瘤细胞DNA、RNA含量增高，致肿瘤生长速度加快。实际上，人体肿瘤与动物实验的肿瘤有较大的差别。动物移植性肿瘤倍增时间短，增长迅速，死亡快，肿瘤占总体的30%以上，这些特点可能是实验性肿瘤对营养缺乏较为敏感的原因。而人体肿瘤增长速度相对较慢，一般不超过总体的5%，实体瘤的平均倍增时间为100天。因此，必要的营养支持不可能在短期内对肿瘤的增长产生很大的影响。
; v+ R- a4 U. x ]. O根据大量的氨基酸与肿瘤生长的研究发现，平衡氨基酸能促使肿瘤细胞蛋白质合成加速，S期细胞百分比增加，有丝分裂活性增强，使肿瘤体积增长迅速，而高浓度精氨酸、蛋氨酸缺乏的不平衡氨基酸可使肿瘤细胞的增殖受到抑制。6 K- c9 g/ k) i2 y
根据某些氨基酸在肿瘤生长中的特殊作用和肿瘤细胞的代谢特点，人为地改变氨基酸的常规剂量，制成某种氨基酸过量或减少乃至缺失的氨基酸失衡液为肿瘤病人进行营养支持，以达到抑制肿瘤生长又能改善病人营养状况的目的。目前研究较多的有去L－缬氨酸失衡液、去L－蛋氨酸失衡液、去L－苯丙氨酸/酪氨酸失衡液，以及L－精氨酸增量失衡液等。
( d0 j }2 x! H- J% n5 G蛋白质的摄入过低或过高均会促进肿瘤的生长。蛋白质的摄入量应适量。一般成年人蛋白质占总热能的12％—15％，每天摄入70—80g为宜。5 K: p- f# r, G% @, m/ h; d1 j
恶性肿瘤患者血清锌降低、铜升高，铜/锌比值升高可见于任何部位的恶性肿瘤，是恶性肿瘤的共同特征。一般认为，肿瘤浸润范围越广、病期越晚，血清铜越高、锌越低。血清铜越高，患者的生存期越短，预后越差。
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Enobosarm improves muscle wasting experienced by patients with NSCLC.
6 N0 y0 H4 r; P: s; i! E- ~http://ecancer.org/news/4073-emc ... ents-with-nsclc.php
' I6 T/ G" p1 ?- {$ @8 \A randomised, double-blind, placebo controlled phase IIB trial shows that treatment with enobosarm, a non-steroidal selective androgen receptor modulator, significantly improved one measure of physical function and increased lean muscle mass in cancer patients overall and specifically in a cohort of patients with non-small cell lung cancer (NSCLC).
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Dr Christopher Croot of the Department of Hematology and Oncology, North Mississippi Hematology and Oncology Associates, Ltd. Tupelo, USA is a first author of the study which findings were complied in a poster-discussion and presented at the European Multidisciplinary Conference in Thoracic Oncology (EMCTO).
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Muscle wasting is a hallmark of cachexia which is caused by byproducts produced by some forms of cancer or by the body's reaction to it.: h7 g- n# [6 h: u4 K
- F; O5 a/ F. y% L$ s* N aMuscle wasting typically affects skeletal muscles, negatively affecting physical function.( f! d0 k y. D/ b7 n5 `
- x' R- O1 u0 X8 I" N. z6 zIt is estimated that more than 50% of lung cancer patients already demonstrate muscle wasting at diagnosis, which increases to affect more than 80% of patients prior to dying from their disease.
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Enobosarm is non-steroidal selective androgen receptor modulator that is tissue-selective and has anabolic effects in muscle and bone, thus increasing lean body mass.
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8 Z/ k' A' S R, ~# EThis randomised, double-blind, placebo controlled study evaluated the effect of enobosarm on lean body mass and physical function in a subset of NSCLC patients.
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9 G8 w5 [; Z" ]9 p9 ~The study enrolled males aged 45 years or more and postmenopausal females, who experienced weight loss of 2% or more over the preceding 6 months. The study participants had been diagnosed with NSCLC, colorectal cancer, non-Hodgkin’s lymphoma, chronic lymphocytic leukaemias, or breast cancer.1 a2 E- y7 O7 a! f3 {) t% v
; Q6 A2 S: W( qThe study primary and secondary endpoints were change in lean body mass as determined by dual energy X-ray absorptiometry (DEXA) scan and physical function measured by stair climb power, respectively. Response was defined as either a 10% improvement in stair climb power or no loss in lean body mass." o5 c( n& \9 P( m& u5 W
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A total of 159 study participants, including a subset comprised of 61 patients with NSCLC, received enobosarm at doses of 1mg or 3mg or placebo for 16 weeks. At 16 weeks, patients treated with enobosarm achieved statistically significant improvements compared to baseline in stair climb power and lean body mass that were not seen in the patients who received placebo.% f4 y, @- e, }" O2 J' u
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Among 28 NSCLC patients who were evaluable for stair climb power, 18 enobosarm treated subjects showed an improvement of median 17% over baseline that was statistically significant (p=0.007). Among the 31 NSCLC subjects who were evaluable for lean body mass, the enobosarm cohort of 21 patients showed a median 1.0 kg increase in lean body mass; whereas, a 0.8 kg loss of lean body mass was observed in patients receiving placebo. The responder analysis demonstrated that 78% and 67% of enobosarm treated patients met the criteria defining stair climb power and lean body mass response, respectively.' ^# d6 c/ F+ ~+ q; ^7 A
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Enobosarm was well tolerated and commonly reported adverse events were consistent with adverse events seen with chemotherapy and included fatigue, anaemia, nausea, and diarrhoea.
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1 j; |" e4 o# G6 c7 k bOn Friday April 12, 2013, an independent Data Safety Monitoring Board (DSMB) announced that a per protocol safety review of unblinded safety data supported the two pivotal phase III clinical trials of enobosarm that are ongoing to determine the prevention and treatment of muscle wasting in patients with advanced NSCLC.
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During the time foreseen for questions and answers, the first author of the study said that two ongoing phase III studies evaluate enobosarm with different type of chemotherapy, one investigate platinum and taxane-based chemotherapy, while the second evaluate platinum and non-taxane regimen. It is important because it is well known that chemotherapy itself can treat symptoms in patients with NSCLC. Each of these phase III studies enrolled 320 patients. The last patient has been enrolled last week. The second point raised during the discussion was that the study authors did not prospectively investigate on the use of glucocorticoids. It would be also important in such studies to test androgen receptor in tumour tissue, however the study presenter said that it has been for a long time speculated on role of testosterone and more lung cancer rates in men than in women, however he doesn't believe the androgen receptor has a major impact on the outcome in NSCLC.
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