Steward W P, Verweij J, Somers R, Blackledge G, Clavel M, Van Oosterom A T, Greifenberg B, Soedirman J, Thomas D, Van Glabbeke M
Beatson Oncology Centre, Western Infirmary, Glasgow, UK.
J Cancer Res Clin Oncol. 1991;117 Suppl 4(Suppl 4):S193-7. doi: 10.1007/BF01613226.
Doxorubicin and ifosfamide are the two most active agents used in the treatment of advanced inoperable soft-tissue sarcoma, but their use in combination produces dose-limiting myelosuppression. To explore the feasibility of combining optimal doses of both drugs, doxorubicin (75 mg/m2) and ifosfamide (5 g/m2) were given every 3 weeks with recombinant human granulocyte/macrophage-colony-stimulating factor (rhGM-CSF; 250 micrograms m-2 day-1) by subcutaneous injection for up to 14 days after each course. A total of 52 patients with progressive metastatic soft-tissue sarcoma were entered, none having received prior chemotherapy. One patient was ineligible and received no treatment after registration. Preliminary analysis of six cycles of chemotherapy revealed that the full protocol dose intensity had been administered to the majority of patients. Although the median leucocyte and neutrophil counts did not fall with subsequent courses of chemotherapy, the duration of neutropenia increased with each course delivered. Cumulative thrombocytopenia was a major dose-limiting toxicity and was the main reason for any dose modifications that occurred. Although 26 patients experienced infections after one or more courses of treatment, in only 7 was admission required for parenteral antibiotics. One patient died as a result of septicaemia after the first cycle of treatment. To date, there have been 22 responses (43%) with 8% complete remissions. It appears that the administration of rhGM-CSF allows this high-dose regime of chemotherapy to be given safely and the early encouraging response rate adds support to the concept that increasing the dose of doxorubicin improves the outlook for patients with advanced soft-tissue sarcomas.
阿霉素和异环磷酰胺是用于治疗晚期无法手术切除的软组织肉瘤的两种最有效的药物，但它们联合使用会产生剂量限制性骨髓抑制。为了探索联合使用两种药物最佳剂量的可行性，每3周给予阿霉素（75mg/m²）和异环磷酰胺（5g/m²），并在每个疗程后皮下注射重组人粒细胞/巨噬细胞集落刺激因子（rhGM-CSF；250μg/m²·天），持续14天。共有52例转移性软组织肉瘤进展期患者入组，均未接受过先前的化疗。1例患者不符合入组标准，登记后未接受治疗。对六个化疗周期的初步分析显示，大多数患者接受了完整方案的剂量强度。虽然白细胞和中性粒细胞计数中位数在后续化疗疗程中未下降，但中性粒细胞减少的持续时间随每个疗程而增加。累积血小板减少是主要的剂量限制性毒性，也是进行任何剂量调整的主要原因。虽然26例患者在一个或多个疗程的治疗后发生感染，但只有7例需要静脉使用抗生素住院治疗。1例患者在第一个治疗周期后因败血症死亡。迄今为止，有22例缓解（43%），其中8%为完全缓解。看来，rhGM-CSF的使用使这种高剂量化疗方案能够安全给药，早期令人鼓舞的缓解率支持了增加阿霉素剂量可改善晚期软组织肉瘤患者预后的概念。
