Edelman M J, Gandara D R, Meyers F J, Ishii R, O'Mahony M, Uhrich M, Lauder I, Houston J, Gietzen D W
Division of Hematology/Oncology, University of California-Davis, Sacramento, California, USA.
Cancer. 1999 Aug 15;86(4):684-8.
Imbalanced amino acid diets in animals rapidly produce anorexia and weight loss. Blockade of type 3 serotonergic receptors (5HT(3)) can ameliorate anorexia in this animal model. Imbalanced plasma amino acid levels also have been documented in both animal models and human patients with cancer cachexia. Therefore a trial of the 5HT(3) receptor antagonist, ondansetron, was undertaken in the treatment of patients with cancer cachexia.
Patients with metastatic cancer who were not undergoing chemotherapy or radiotherapy and who had lost >5% of their body weight were eligible. Baseline physical examination; weight; anthropometric studies; levels of retinol binding protein, albumin, and prealbumin; and skin testing for anergy were obtained. The ability to enjoy food was assessed utilizing a seven-point hedonic category scale for specific foods. Therapy was comprised of oral ondansetron, 8 mg twice a day.
Twenty-seven patients were enrolled; all were evaluable for toxicity and 20 patients were evaluable for response. Toxicity of ondansetron was minimal. Patients demonstrated significant weight loss prior to disease entry (mean baseline weight of 76.9 kg vs. 72. 1 kg; P < 0.000002). Patients continued to lose weight on study (Week 0: 72.5 kg vs. Week 4: 71.4 kg; P = 0.027); in addition, there was significant deterioration of midarm circumference and hand grip strength, all of which indicated worsening nutritional status. However, a significant improvement in food enjoyment was noted (P = 0.04).
Although it apparently improved the ability of patients to enjoy food, the blockade of 5HT(3) receptors failed to prevent weight loss in patients with cancer cachexia or alter laboratory parameters of protein nutrition.
动物摄入氨基酸不均衡的饮食会迅速导致厌食和体重减轻。在这种动物模型中，阻断3型血清素能受体（5HT(3)）可改善厌食症状。动物模型和癌症恶病质的人类患者中也都记录到血浆氨基酸水平失衡。因此，开展了一项使用5HT(3)受体拮抗剂昂丹司琼治疗癌症恶病质患者的试验。
未接受化疗或放疗且体重减轻超过5%的转移性癌症患者符合条件。进行了基线体格检查、体重测量、人体测量学研究、视黄醇结合蛋白、白蛋白和前白蛋白水平检测以及皮肤无反应性测试。使用针对特定食物的七点享乐类别量表评估对食物的喜好程度。治疗方案为口服昂丹司琼，每日两次，每次8毫克。
招募了27名患者；所有患者均可评估毒性，20名患者可评估疗效。昂丹司琼的毒性极小。患者在入组前体重显著下降（平均基线体重76.9千克对72.1千克；P < 0.000002）。在研究过程中患者体重持续下降（第0周：72.5千克对第4周：71.4千克；P = 0.027）；此外，上臂围和握力显著恶化，所有这些均表明营养状况恶化。然而，食物喜好程度有显著改善（P = 0.04）。
尽管5HT(3)受体阻断剂似乎改善了患者对食物的喜好能力，但未能防止癌症恶病质患者体重减轻，也未改变蛋白质营养的实验室参数。
