Lokich J J, Egorin M J, Cohen B E, Bern M M, Zipoli T E, Moore C
Division of Medical Oncology, Cancer Center, Inc., Medical Center of Boston, MA 02120.
Cancer. 1989 Jan 1;63(1):46-50. doi: 10.1002/1097-0142(19890101)63:1<46::aid-cncr2820630107>3.0.co;2-y.
Forty-five patients received escalating dose rates of continuous infusion thio-triethylene thiophosphoramide (TEPA) for either five (26 patients) or 28 (19 patients) days. Dose rate limiting toxicity for the 5-day infusion was myelosuppression with leukocyte and platelet nadirs on days 21 and 28, respectively. The nadir was influenced by the presence and degree of liver disease. The optimal dose rate for 5-day infusion in the absence of liver disease was 12 mg/m2/d and was reduced to 8 mg/m2/d in patients with major liver disease. Dose rate limiting toxicity for the protracted 28-day infusion was leukopenia. The optimal dose rate for the 28-day infusion was 4 mg/m2/d. Pharmacologic studies included determination of plasma steady state concentrations (CSS) of thio-TEPA and TEPA. Dose rates up to 10 mg/m2/d produced thio-TEPA and TEPA CSS below the levels of detection of available analytical methodology, except in three patients infused at dose rates of 1, 2, and 4 mg/m2/d, respectively.
45例患者接受了持续递增剂量率的硫代三乙烯硫代磷酰胺（TEPA）静脉输注，疗程分别为5天（26例患者）或28天（19例患者）。5天输注的剂量限制性毒性为骨髓抑制，白细胞和血小板最低点分别出现在第21天和第28天。最低点受肝病的存在和程度影响。无肝病患者5天输注的最佳剂量率为12mg/m²/d，重度肝病患者则降至8mg/m²/d。延长至28天输注的剂量限制性毒性为白细胞减少。28天输注的最佳剂量率为4mg/m²/d。药理学研究包括测定硫代TEPA和TEPA的血浆稳态浓度（CSS）。除了分别以1、2和4mg/m²/d的剂量率输注的3例患者外，高达10mg/m²/d的剂量率产生的硫代TEPA和TEPA CSS低于现有分析方法的检测水平。
