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高剂量持续输注异环磷酰胺治疗晚期高分化/去分化脂肪肉瘤

High-dose continuous-infusion ifosfamide in advanced well-differentiated/dedifferentiated liposarcoma.

作者信息

Sanfilippo Roberta, Bertulli Rossella, Marrari Andrea, Fumagalli Elena, Pilotti Silvana, Morosi Carlo, Messina Antonella, Dei Tos Angelo Paolo, Gronchi Alessandro, Casali Paolo Giovanni

机构信息

Adult Mesenchymal Tumor Medical Oncology Unit, Cancer Medicine Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Via G. Venezian 1, 20133 Milano, Italy.

Experimental Molecular Pathology Unit, Department of Pathology, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy.

出版信息

Clin Sarcoma Res. 2014 Nov 22;4(1):16. doi: 10.1186/2045-3329-4-16. eCollection 2014.

Abstract

BACKGROUND

Liposarcomas represent the most common histological type of soft-tissue sarcomas (STS). Its main subgroups, WD/DD, is known to be poorly sensitive to chemotherapy, with few active agents, i.e., anthracyclines +/- ifosfamide and trabectedin. High-dose ifosfamide (HDIFX >12 g/m2) is active in STS pts pretreated with standard-dose IFX, though with greater toxicity. A prolonged continuous-infusion (ci) through a portable external pump may be an alternative way to administer HDIFX.

METHODS

From March 2002 to August 2013, 28 pts (median age =60, range =37-73 yrs) with advanced disease (6 WD and 22 WD/DD) were given ciHDIFX, at the dose of 14 g/m2 as a 14-day continuous infusion every 4 weeks. Twenty-four pts (86%) were previously treated with chemotherapy (19 with anthracyclines and ifosfamide; 4 with anthracycline monotherapy; 1 with trabectedin).

RESULTS

Seven PR (all in DDLPS), 2 minor response (MR) and 11 SD were observed. Of interest, 6 of 9 patients with PR or MR had had SD with the previous therapy with anthracycline plus ifosfamide. The median progression-free survival was 7 months. Most common side effects were mild myelosuppression (anemia G2-3 in 3 pts; G2-3 neutropenia in 3 pts and G4 in 1; G3 thrombocytopenia in 1 pt); nausea (G3 in 3 pts) and fatigue (G3 in 6 pts). One pts had transient G3 confusion.

CONCLUSIONS

These data suggest that ciHDIFX is active in WD/DDLPS, even in patients already treated with a combination of anthracyclines plus ifosfamide. In this series, ciHDIFX regimen was better tolerated than HDIFX in published studies.

摘要

背景

脂肪肉瘤是软组织肉瘤(STS)中最常见的组织学类型。其主要亚组,即去分化/多形性脂肪肉瘤(WD/DD),已知对化疗敏感性较差,有效的药物很少,即蒽环类药物+/-异环磷酰胺和曲贝替定。高剂量异环磷酰胺(HDIFX>12 g/m2)对接受过标准剂量异环磷酰胺(IFX)预处理的STS患者有效,尽管毒性更大。通过便携式外部泵进行长时间持续输注(ci)可能是给予HDIFX的另一种方式。

方法

从2002年3月至2013年8月,28例晚期疾病患者(中位年龄=60岁,范围=37-73岁)(6例去分化脂肪肉瘤和22例去分化/多形性脂肪肉瘤)接受ciHDIFX治疗,剂量为14 g/m2,每4周进行14天持续输注。24例患者(86%)先前接受过化疗(19例接受蒽环类药物和异环磷酰胺治疗;4例接受蒽环类药物单药治疗;1例接受曲贝替定治疗)。

结果

观察到7例部分缓解(PR)(均为多形性去分化脂肪肉瘤)、2例轻微缓解(MR)和11例疾病稳定(SD)。有趣的是,9例PR或MR患者中有6例在先前接受蒽环类药物加异环磷酰胺治疗时疾病稳定。中位无进展生存期为7个月。最常见的副作用是轻度骨髓抑制(3例患者出现2-3级贫血;3例患者出现2-3级中性粒细胞减少,1例出现4级;1例患者出现3级血小板减少);恶心(3例患者出现3级)和疲劳(6例患者出现3级)。1例患者出现短暂的3级意识模糊。

结论

这些数据表明,ciHDIFX对去分化/多形性脂肪肉瘤有效,即使是已接受蒽环类药物加异环磷酰胺联合治疗的患者。在本系列中,ciHDIFX方案的耐受性优于已发表研究中的HDIFX。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4c5f/4307996/58f181c8d1c5/13569_2014_66_Fig1_HTML.jpg

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