Takvorian T, Parker L M, Hochberg F H, Canellos G P
J Clin Oncol. 1983 Oct;1(10):610-20. doi: 10.1200/JCO.1983.1.10.610.
Thirty-five patients with solid tumors received 44 courses of bis-chlorethylnitrosourea (BCNU) at doses ranging between 600 and 1,400 mg/m2 with cryopreserved or fresh autologous bone-marrow support. Eight patients treated at 600 mg/m2 received no bone-marrow support for their first course of BCNU. Maximum follow-up was 25 months (median, four months). Myelosuppression was severe and dose related but was less prolonged in the marrow-supported groups (p = 0.01) and was not dose limiting. Myelosuppression-related toxicity of infection and hemorrhage occurred in 21 (47%) of 44 courses of treatment. Pulmonary toxicity occurred in seven of 35 patients; abnormal liver function occurred in 18 of 30 patients greater than one month from treatment; and central nervous system symptoms that may have been drug related occurred in six of 35 patients. There was no renal or cardiac toxicity. Except for myelosuppression, toxicity was not dose related. Treatment-related deaths included four with pulmonary toxicity, two with liver toxicity, sepsis in four, and gastrointestinal tract toxicity in one patient. We conclude that the limiting side effect of high-dose BCNU (greater than or equal to 600 mg/m2) is visceral toxicity; the extent of myelosuppression is shortened by the infusion of bone marrow, whether cryopreserved or fresh; and marked tumor regression can be achieved with high-dose BCNU.
35例实体瘤患者接受了44个疗程的双氯乙基亚硝脲（BCNU）治疗，剂量范围为600至1400mg/m²，并辅以冷冻保存或新鲜的自体骨髓支持。8例接受600mg/m²治疗的患者在其第一个BCNU疗程中未接受骨髓支持。最长随访时间为25个月（中位数为4个月）。骨髓抑制严重且与剂量相关，但在骨髓支持组中持续时间较短（p = 0.01），且不是剂量限制性的。44个疗程中有21个（47%）出现了与骨髓抑制相关的感染和出血毒性。35例患者中有7例出现肺部毒性；治疗后1个月以上的30例患者中有18例出现肝功能异常；35例患者中有6例出现可能与药物相关的中枢神经系统症状。未出现肾毒性或心脏毒性。除骨髓抑制外，毒性与剂量无关。与治疗相关的死亡包括4例肺部毒性、2例肝脏毒性、4例败血症和1例胃肠道毒性。我们得出结论，高剂量BCNU（大于或等于600mg/m²）的限制性副作用是内脏毒性；无论输注冷冻保存的还是新鲜的骨髓，骨髓抑制的程度都会缩短；高剂量BCNU可实现显著的肿瘤消退。
