靶向尤因肉瘤中的EWS-FLI1转录因子。
Targeting the EWS-FLI1 transcription factor in Ewing sarcoma.
作者信息
Tancredi R, Zambelli A, DaPrada G A, Fregoni V, Pavesi L, Riccardi A, Burdach S, Grohar P J, D'Incalci M
机构信息
Medical Oncology Unit, I.R.C.C.S. Salvatore Maugeri Foundation, Via Salvatore Maugeri, 10, 27100, Pavia, Italy.
出版信息
Cancer Chemother Pharmacol. 2015 Jun;75(6):1317-20. doi: 10.1007/s00280-015-2726-7. Epub 2015 Mar 26.
PURPOSE
Preclinical data indicate there is strong synergism of action against Ewing sarcoma in sequential treatment with trabectedin followed by irinotecan and it appears to be related to a selective blockade of the transcription factor EWS-FLI1. This combination was evaluated in Ewing sarcoma patient who was progressing with standard therapies.
METHODS
Trabectedin was given as a 24-h iv infusion on day 1 at the dose of 1 mg/sqm, and irinotecan 75 mg/sqm on day 2 and then on days 2 and 4, every 3 weeks from the seventh course.
RESULTS
The therapy was well tolerated with transient hematological toxicity and transaminitis and induced stabilization of the disease lasting for 11 courses, with clinical improvement and marked reduction of the need for opioids. However, shortly before the 12th course, sudden death occurred, possibly due to cerebral stroke, presumably not related to the drug treatment.
CONCLUSIONS
The encouraging clinical benefit observed with the combination and its good tolerability deserves further investigation in Ewing sarcoma.
目的
临床前数据表明，曲贝替定序贯伊立替康治疗尤因肉瘤具有强大的协同作用，且这种协同作用似乎与转录因子EWS-FLI1的选择性阻断有关。对接受标准治疗病情进展的尤因肉瘤患者进行了该联合治疗的评估。
方法
第1天给予曲贝替定，剂量为1mg/m²，静脉输注24小时，第2天给予伊立替康75mg/m²，然后从第7疗程开始，每3周在第2天和第4天给药。
结果
该治疗耐受性良好，有短暂的血液学毒性和转氨酶升高，并使疾病稳定持续11个疗程，临床症状改善，对阿片类药物的需求显著减少。然而，在第12疗程前不久，患者突然死亡，可能是由于脑卒所致，推测与药物治疗无关。
结论
该联合治疗观察到的令人鼓舞的临床获益及其良好的耐受性值得在尤因肉瘤中进一步研究。
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