Randomized phase II evaluation of 6 g/m2 of ifosfamide plus doxorubicin and granulocyte colony-stimulating factor (G-CSF) compared with 12 g/m2 of ifosfamide plus doxorubicin and G-CSF in the treatment of poor-prognosis soft tissue sarcoma
Randomized phase II evaluation of 6 g/m2 of ifosfamide plus doxorubicin and granulocyte colony-stimulating factor (G-CSF) compared with 12 g/m2 of ifosfamide plus doxorubicin and G-CSF in the treatment of poor-prognosis soft tissue sarcoma
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DOI：
10.1200/jco.2005.05.108
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发表时间：
2005-01-01
影响因子：
45.3
通讯作者：
Baker, LH
中科院分区：
文献类型：
--
作者：
Worden, FP;Taylor, JMG;Baker, LH
目的在软组织肉瘤患者联合化疗中增加异环磷酰胺剂量的相对价值尚不清楚。本研究的目的是比较阿霉素与大剂量异环磷酰胺(HD)和标准剂量异环磷酰胺(SD)治疗STS的疗效和毒性。STS患者随机分为阿霉素60 mg/m(2)，SD异环磷酰胺1.5g/m(2)/d，第1~4天，HD异环磷酰胺3.0g/m(2)，第1~4天，每21天一次。根据有无转移性疾病对患者进行分层。研究终点为总生存期(OS)、1年无瘤生存期(DFS)和毒副作用。结果研究组79例，其中局部病变52例，转移瘤27例。在已知的预后因素方面，两组患者都达到了良好的平衡。SD异环磷酰胺与HD异环磷酰胺相比，1年DFS无显著差异(55%vs52%；P=.81)。SD异环磷酰胺2年和3年OS分别为73%和52%，HD异环磷酰胺分别为57%和49%(P=0.34)。SD异环磷酰胺组3/4度中性粒细胞减少、贫血和血小板减少的发生率分别为49%、23%和10%，而HD异环磷酰胺组分别为88%、58%和63%。5例早期死亡均发生在HD异环磷酰胺臂上。结论HD异环磷酰胺与阿霉素联合应用并不能改善1年的DFS和OS。HD异环磷酰胺组的毒性明显更大，结果差异的缺乏可能是HD异环磷酰胺的毒性所致。这些结果提示HD异环磷酰胺联合方案不应作为STS患者的一线治疗方案。
Purpose The relative value of increasing ifosfamide dose in combination chemotherapy for patients with soft tissue sarcoma (STS) is unclear. The purpose of this study was to compare the efficacy and toxicity of doxorubicin with high-dose (HD) ifosfamide or standard-dose (SD) ifosfamide in patients with STS.Patients and Methods Chemotherapy-naive patients with STS were randomly assigned to receive doxorubicin 60 mg/m(2) and either SD ifosfamide (1.5 g/m(2)/d, days 1 through 4) or HD ifosfamide (3.0 g/m(2) days I through 4) every 21 days. Patients were stratified by the presence or absence of metastatic disease. End points were overall survival (OS), 1-year disease-free survival (DFS), and toxicity.Results The study group consisted of 79 patients (52 patients with localized disease and 27 patients with metastases). Both groups were well-balanced with respect to known prognostic factors. There was no significant difference in 1-year DFS comparing SD ifosfamide with HD ifosfamide (55% v 52%; P = .81). For SD ifosfamide, 2- and 3-year OS were 73% and 52% versus 57% and 49% for HD ifosfamide (P = .34). The incidence of grade 3/4 neutropenia, anemia, and thrombocytopenia were 49%, 23%, and 10%, respectively, on the SD ifosfamide arm, compared with 88%, 58%, and 63%, respectively, on the HD ifosfamide arm. There were five early deaths, all on the HD ifosfamide arm.Conclusion When combined with doxorubicin, HD ifosfamide did not improve 1-year DFS and OS. Toxicity was clearly greater with the HD ifosfamide arm, and lack of outcome differences might be explained by toxicities with HD ifosfamide. These results suggest that HD ifosfamide combination regimens should not be used as first-line therapy for patients with STS.