Aisner J, Tchekmedyian N S, Tait N, Parnes H, Novak M
University of Maryland, Cancer Center, Baltimore 21201.
Semin Oncol. 1988 Apr;15(2 Suppl 1):68-75.
Cachexia can be a severe problem in the management of patients with cancer and other illnesses because it produces an ever-increasing spiral of anorexia, undernutrition, loss of tissue mass, muscle wasting, and increased susceptibility to infection and treatment toxicity. Megestrol acetate has been observed to produce weight gain in patients with hormone-sensitive tumors and has recently been noted to produce a similar degree of weight gain in those with hormone insensitive tumors. A review of our experience in a phase I-II study of escalating doses of megestrol acetate for advanced breast cancer revealed that weight gain occurred in more than 80% of all treated patients and in 90% of those patients who received treatment for 6 or more weeks. The median maximum weight gain was 5.5 kg, with a range of -5.6 to 44 kg. Subjective improvement in appetite occurred in most patients. These data provided the impetus for a series of further studies of the role of megestrol acetate in the control of cachexia, including a randomized study in cancer cachexia, AIDS cachexia, and anorexia nervosa. In addition, a number of laboratory trials seeking the mechanism of action have been initiated, as well as whole-animal studies to define the compartment of increased weight. Our data and the preliminary observation of weight gain in patients with hormone insensitive tumors suggest that megestrol acetate has a potential role in producing a possibly dose-related subjective improvement and an increase in appetite and weight. Further research is necessary to understand the mechanism of appetite stimulation and anabolic effect.
恶病质在癌症和其他疾病患者的治疗中可能是一个严重问题，因为它会导致厌食、营养不良、组织量减少、肌肉萎缩以及感染易感性和治疗毒性增加的恶性循环。已观察到醋酸甲地孕酮可使激素敏感性肿瘤患者体重增加，最近还发现它能使激素不敏感性肿瘤患者体重有相似程度的增加。回顾我们在一项针对晚期乳腺癌递增剂量醋酸甲地孕酮的I-II期研究中的经验发现，超过80%的所有接受治疗的患者出现体重增加，在接受治疗6周或更长时间的患者中这一比例为90%。最大体重增加中位数为5.5kg，范围为-5.6至44kg。大多数患者食欲有主观改善。这些数据推动了一系列关于醋酸甲地孕酮在控制恶病质中作用的进一步研究，包括一项针对癌症恶病质、艾滋病恶病质和神经性厌食症的随机研究。此外，已经启动了一些寻找作用机制的实验室试验，以及确定体重增加部位的全动物研究。我们的数据以及激素不敏感性肿瘤患者体重增加的初步观察结果表明，醋酸甲地孕酮在产生可能与剂量相关的主观改善以及增加食欲和体重方面具有潜在作用。需要进一步研究以了解食欲刺激和合成代谢作用的机制。
