Leber H, Kotz R, Chiari K, Endler T, Gabl F, Krisch K, Salzer-Kuntschik M
Wien Klin Wochenschr. 1981 Apr 3;93(7):236-40.
9 HDMTX infusions with 30 to 55 g MTX and leucovorin rescue were given to 3 patients with multifocal osteosarcoma. Resistance to standard MTX infusions with up to 12 g/m2 body surface in 4 hours indicated the administration of these higher doses (27 g/m2 body surface on average) over a shorter period of time (160 min on average). MTX input was controlled by the increase in plasma MTX levels which were determined by EMIT enzyme assay within a few minutes of sampling. The plasma MTX levels were found to be up to 10 times (average 4 times) higher than those achieved by the standard infusion. All infusions proved to be relatively well tolerated in all 3 cases, although, thrice after 36 hours an increased leucovorin rescue had to be made for 12 hours, because of delayed renal methotrexate excretion; the usual leucovorin rescue (15 mg every 6 hours) was given for an average of five days. No therapeutic effects were seen either clinically, radiologically, or histologically. The resistance to HDMTX in these three patients could not be broken by HDMTX PLRD infusions.
对3例多灶性骨肉瘤患者进行了9次高剂量甲氨蝶呤（HDMTX）输注，每次输注30至55克甲氨蝶呤（MTX）并进行亚叶酸钙解救。对4小时内给予高达12克/平方米体表面积的标准MTX输注产生耐药，表明需在更短时间（平均160分钟）内给予更高剂量（平均27克/平方米体表面积）。MTX输入量通过血浆MTX水平的升高来控制，血浆MTX水平在采样后几分钟内通过EMIT酶法测定。发现血浆MTX水平比标准输注所达到的水平高出10倍（平均4倍）。在所有3例病例中，所有输注的耐受性相对良好，不过，有3次在36小时后，由于甲氨蝶呤经肾脏排泄延迟，不得不增加亚叶酸钙解救剂量并持续12小时；通常的亚叶酸钙解救（每6小时15毫克）平均给予5天。在临床、放射学或组织学方面均未观察到治疗效果。这3例患者对HDMTX的耐药性无法通过HDMTX PLRD输注来克服。
