Bacci G, Ferrari S, Picci P, Zolezzi C, Gherlinzoni F, Iantorno D, Cazzola A
Sezione di Chemioterapia dei Tumori dell' Apparato Locomotore, Università di Bologna, Italy.
J Chemother. 1996 Dec;8(6):472-8. doi: 10.1179/joc.1996.8.6.472.
The authors investigated the influence of methotrexate (MTX) serum concentration on (histologically evaluated) tumor necrosis, induced by a primary multiagent chemotherapy, including MTX, for osteosarcoma. MTX serum peaks in 151 patients, preoperatively treated with MTX (8-12g/m2), cisplatin (120mg/m2) and Adriamycin (60mg/m2), were analyzed. Significantly (p < 0.01) higher serum MTX mean peaks were observed in patients with complete tumor necrosis (MTX 773.8 mumol/l) compared to patients with 90-99% tumor necrosis (639.8 mumol/l), 50-89% tumor necrosis (649.1 mumol/l) or less than 50% tumor necrosis (610 mumol/l). Complete tumor necrosis was observed in 9% of patients with MTX peaks of less than 600 mumol/l, in 27% of patients with serum MTX peaks between 600 and 699 mumol/l and in 37% of those with MTX peaks ranging from 700 to 799 mumol/l. Higher MTX peaks (800-899, 900-999, > 1000 mumol/l) were not associated with a further increase of cases with complete tumor necrosis. 40% of patients with an MTX peak greater than 700 mumol/l had complete tumor necrosis, compared to 15.5% of patients who did not reach this value (p < 0.002). At a multivariant analysis including age, sex, tumor site and volume, pretreatment serum alkaline phosphatase and lactic dehydrogenase levels, MTX peaks of 700 mumol/l and, less significantly, the histologic type (telangiectatic osteosarcoma), were independent factors influencing tumor necrosis. The authors conclude that MTX serum peaks significantly influence chemotherapy-induced tumor necrosis in osteosarcoma. In a primary treatment consisting of cisplatin, Adriamycin and MTX, complete tumor necrosis can be obtained in 40% of patients with MTX peak concentrations > or = 700 mumol/l.
作者研究了甲氨蝶呤（MTX）血清浓度对骨肉瘤多药联合化疗（包括MTX）诱导的（组织学评估的）肿瘤坏死的影响。分析了151例术前接受MTX（8 - 12g/m²）、顺铂（120mg/m²）和阿霉素（60mg/m²）治疗患者的MTX血清峰值。与肿瘤坏死90 - 99%（639.8μmol/l）、50 - 89%（649.1μmol/l）或小于50%（610μmol/l）的患者相比，肿瘤完全坏死的患者（MTX 773.8μmol/l）血清MTX平均峰值显著更高（p < 0.01）。MTX峰值低于600μmol/l的患者中9%出现肿瘤完全坏死，血清MTX峰值在600至699μmol/l之间的患者中27%出现，MTX峰值在700至799μmol/l之间的患者中37%出现。更高的MTX峰值（800 - 899、900 - 999、>1000μmol/l）与肿瘤完全坏死病例的进一步增加无关。MTX峰值大于700μmol/l的患者中有40%出现肿瘤完全坏死，而未达到该值的患者中这一比例为15.5%（p < 0.002）。在包括年龄、性别、肿瘤部位和体积、治疗前血清碱性磷酸酶和乳酸脱氢酶水平的多变量分析中，MTX峰值700μmol/l以及不太显著的组织学类型（毛细血管扩张性骨肉瘤）是影响肿瘤坏死的独立因素。作者得出结论，MTX血清峰值显著影响骨肉瘤化疗诱导的肿瘤坏死。在由顺铂、阿霉素和MTX组成的初始治疗中，MTX峰值浓度≥700μmol/l的患者中有40%可实现肿瘤完全坏死。
