Page R L, Thrall D E, Dewhirst M W, Macy D W, George S L, McEntee M C, Heidner G L, Novotney C A, Allen S A, Withrow S J
North Carolina State University, College of Veterinary Medicine, Raleigh 27606.
Int J Hyperthermia. 1991 Jul-Aug;7(4):559-66. doi: 10.3109/02656739109034968.
The maximum tolerated dose of melphalan combined with whole body hyperthermia (WBH) in dogs with spontaneous malignant melanoma was lower than in dogs not receiving WBH by a factor of 1.9 +/- 0.71. Thirty-three dogs were treated monthly with escalating doses of melphalan and followed weekly for toxicity and, when possible, tumour response. Toxicity was manifested as myelosuppression with nadir neutrophil and platelet counts occurring at 7-10 days post-treatment. The TD50 (+/- S.E.), defined by logistic regression analysis, was 0.63 (+/- 0.07) mg/kg and 0.33 (+/- 0.10) mg/kg for melphalan alone and combined with WBH, respectively. Objective tumour response in this limited series occurred in three of fourteen evaluable dogs (three of eleven treated with melphalan alone and none of three treated with WBH plus melphalan). It is concluded that melphalan combined with WBH can be safely administered, although a reduction in dose is necessary. A randomized clinical trial is required to investigate the possibility of achieving therapeutic benefit from combined melphalan and WBH.
在患有自发性恶性黑色素瘤的犬中，美法仑联合全身热疗（WBH）的最大耐受剂量比未接受WBH的犬低1.9±0.71倍。33只犬每月接受递增剂量的美法仑治疗，并每周监测毒性，如有可能，监测肿瘤反应。毒性表现为骨髓抑制，治疗后7 - 10天出现中性粒细胞和血小板计数最低点。通过逻辑回归分析确定的TD50（±标准误），单独使用美法仑时为0.63（±0.07）mg/kg，联合WBH时为0.33（±0.10）mg/kg。在这个有限的系列中，14只可评估犬中有3只出现客观肿瘤反应（单独使用美法仑治疗的11只中有3只，联合WBH加美法仑治疗的3只中无）。结论是，美法仑联合WBH可以安全给药，尽管有必要降低剂量。需要进行一项随机临床试验来研究联合美法仑和WBH实现治疗益处的可能性。
