Ecteinascidin-743: A marine-derived compound in advanced, pretreated sarcoma patients - Preliminary evidence of activity
Ecteinascidin-743: A marine-derived compound in advanced, pretreated sarcoma patients - Preliminary evidence of activity
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DOI：
10.1200/jco.2001.19.5.1248
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发表时间：
2001-03-01
影响因子：
45.3
通讯作者：
Cvitkovic, E
中科院分区：
文献类型：
--
作者：
Delaloge, S;Yovine, A;Cvitkovic, E
目的：报告在I期研究和基于指定患者的同情使用计划中观察到的化疗药物海鞘素-743（ET-743）在晚期预治疗肉瘤患者中的活性。患者和方法：29名在我们中心连续就诊的预先治疗的晚期软组织肉瘤（STS）和骨肉瘤患者被纳入，12例来自I期试验，17例来自同情使用项目队列。患者每3周接受1，200 mug/m2（6例患者）、1，500 mug/m2（22例患者）或1，800 mug/m2（1例患者）的治疗，每3 - 4周进行24小时输注。患者年龄中位数为46岁（范围：16 - 71岁），世界卫生组织体能状态中位数为1（范围：0 - 2）。25名患者患有STS，3名患有骨肉瘤，1名患有尤文氏肉瘤，所有患者在入组时都有疾病进展。15例患者群庞大的疾病，14例临床耐药性蒽环类药物。共进行了136个治疗周期（每例患者的中位数为5个周期;范围为1 - 12个周期）。分别在24%和5%的周期中报告了一过性3级和4级转氨酶升高，32%的周期中发生了3 - 4级中性粒细胞减少，5.1%的周期中伴有散发性3 - 4级血小板减少。21%的周期发生2 - 3级无力。STS患者中有2例部分缓解（PR），骨肉瘤患者中有2例PR。观察到2例轻微缓解和10例疾病稳定。中位反应持续时间为10.5个月（范围，2.8至15个月），平均持续时间稳定为5.2 months.Conclusion：ET-743具有活性，在先进的，高度预处理STS和骨肉瘤患者，并保证进一步的试验，以建立在这种情况下的IFS活动的程度。J Clin Oncol 19：1248-1255. (C)2001年，美国临床肿瘤学会。
Purpose: To report the activity of the chemotherapeutic agent ecteinascidin-743 (ET-743) in advanced pretreated sarcoma patients observed during a phase I study and a named-patient basis, compassionate use program.Patients and Methods: Twenty-nine pretreated, advanced soft tissue sarcoma (STS) and bone sarcoma patients consecutively seen in our centers were included, 12 from a phase I trial and 17 from a compassionate use program cohort. patients were treated every 3 weeks at either 1,200 mug/m(2) (six patients), 1,500 mug/m(2) (the recommended dose, 22 patients), or 1,800 mug/m(2) (the maximum-tolerated dose, one patient), given as a 24-hour infusion every 3 to 4 weeks.Results: Fifteen men and 14 women were treated. The median patient age was 46 years (range, 16 to 71 years), with a median World Health Organization performance status of 1 (range, 0 to 2). Twenty-five patients had STS, three had osteosarcoma, and one had Ewing's sarcoma, and all had progressive disease at accrual. Fifteen patients herd bulky disease, and 14 had clinical resistance to anthracyclines. A total of 136 treatment cycles were administered (median per patient, five cycles; range, one to 12 cycles). Transient grade 3 and 4 transaminitis was reported in 24% and 5% of cycles, respectively, grade 3 to 4 neutropenia occurred in 32% of cycles, with concomitant sporadic grade 3 to 4 thrombocytopenia in 5.1% of cycles. Grade 2 to 3 asthenia occurred in 21% of cycles. There were two partial responses (PRs) in STS patients and two PRs in osteosarcoma patients. Two minor responses and 10 disease stabilizations were seen. Median duration of response was 10.5 months (range, 2.8 to 15 months), and mean duration of stabilization was 5.2 months.Conclusion: ET-743 has activity in advanced, highly pretreated STS and osteosarcoma patients and warrants further trials to establish the extent of ifs activity in this setting. J Clin Oncol 19:1248-1255. (C) 2001 by American Society of Clinical Oncology.