Steward W P, Verweij J, Somers R, Spooner D, Kerbrat P, Clavel M, Crowther D, Rouesse J, Tursz T, Tueni E
Beatson Oncology Centre, Western Infirmary, Glasgow, Scotland.
Cancer Chemother Pharmacol. 1993;31 Suppl 2:S241-4.
We gave the "optimal" dose of doxorubicin (75 mg/m2) with ifosfamide (5 g/m2), the two most active agents against metastatic soft-tissue sarcomas, in an attempt to determine the feasibility of administration of these doses in combination. To offset complications arising from the myelosuppression associated with this regimen, recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF, 250 micrograms/m2 daily) was given by subcutaneous injection during the intervals between courses of chemotherapy. In all, 111 patients with progressive metastatic soft-tissue sarcoma were entered, 104 of whom were eligible for preliminary analysis. Use of rhGM-CSF allowed full doses of chemotherapy to be given to the majority of patients, although cumulative thrombocytopenia became a dose-limiting toxicity during subsequent courses. Two treatment-related deaths occurred, one from presumed septicemia while the patient was at home and one as a result of cardiac failure. An overall response rate of 45% was achieved. The activity of this high-dose combination (with rhGM-CSF) will be compared with that of standard treatment doses in a future phase III randomized trial.
我们给予阿霉素（75毫克/平方米）与异环磷酰胺（5克/平方米）的“最佳”剂量，这两种药物是针对转移性软组织肉瘤最有效的药物，旨在确定联合使用这些剂量的可行性。为了抵消与该方案相关的骨髓抑制引起的并发症，在化疗疗程的间隔期间，通过皮下注射给予重组人粒细胞-巨噬细胞集落刺激因子（rhGM-CSF，每日250微克/平方米）。总共纳入了111例进展期转移性软组织肉瘤患者，其中104例符合初步分析条件。使用rhGM-CSF使得大多数患者能够接受全剂量化疗，尽管在后续疗程中累积性血小板减少成为剂量限制性毒性。发生了两例与治疗相关的死亡，一例是患者在家时因疑似败血症死亡，另一例是因心力衰竭死亡。总体缓解率为45%。在未来的III期随机试验中，将把这种高剂量联合方案（联合rhGM-CSF）的活性与标准治疗剂量的活性进行比较。
