Results of a phase I dose escalation study of eltrombopag in patients with advanced soft tissue sarcoma receiving doxorubicin and ifosfamide.
Results of a phase I dose escalation study of eltrombopag in patients with advanced soft tissue sarcoma receiving doxorubicin and ifosfamide.
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DOI：
10.1186/1471-2407-13-121
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发表时间：
2013-03-16
期刊：
影响因子：
3.8
通讯作者：
Kamel YM
中科院分区：
文献类型：
--
作者：
Chawla SP;Staddon A;Hendifar A;Messam CA;Patwardhan R;Kamel YM
这项 I 期剂量递增研究的目的是探讨艾曲波帕（一种口服非肽血小板生成素受体激动剂）在因阿霉素和异环磷酰胺 (AI) 联合化疗导致的晚期软组织肉瘤 (STS) 和血小板减少症患者中的安全性和耐受性。 18 岁或以上经组织学证实的局部晚期或转移性 STS 患者接受 1 个周期的 AI 治疗，然后从第 2 个周期开始使用艾曲波帕进行 AI 治疗，采用 2 种不同的给药方案。研究设计包括艾曲波帕剂量递增阶段，从每天 75mg 开始，以确定最佳生物剂量 (OBD)。 18 名患者入组，其中 15 名患者接受了至少 1 剂化疗； 3 名患者在接受艾曲波帕治疗前退出。 7 名、4 名和 1 名患者分别每天接受 75 mg、100 mg 和 150 mg 艾曲波帕。没有报道剂量限制性毒性。由于招募缓慢，该研究在确定 OBD 之前就结束了。最常见的血液学不良事件 (AE) 是血小板减少症 (80%)、中性粒细胞减少症 (73%) 和贫血 (67%)。最常见的非血液学 AE 是疲劳（53%）、丙氨酸转氨酶升高、便秘和恶心（各 47%）。接受艾曲波帕治疗的 12 名患者中有 11 名完成了至少 2 个化疗周期；与第 1 周期的第 1 天（不含艾曲波帕的周期）相比，所有患者在第 2 周期（使用艾曲波帕的周期）第 1 天的血小板计数均有所增加。尽管数据有限，但安全性数据与 AI 联合化疗的已知毒性或其他研究中发现的艾曲波帕的副作用一致。现有数据表明，艾曲波帕联合 AI 化疗时可能存在化疗前和化疗后给药方案，并支持对化疗引起的血小板减少症患者的艾曲波帕治疗进行进一步研究。
The objective of this Phase I dose escalation study was to explore the safety and tolerability of eltrombopag, an oral, nonpeptide, thrombopoietin receptor agonist, in patients with advanced soft tissue sarcoma (STS) and thrombocytopenia due to treatment with doxorubicin and ifosfamide (AI) combination chemotherapy. Patients aged 18 or older with histologically confirmed, locally advanced or metastatic STS were treated with 1 cycle of AI followed by AI with eltrombopag starting at Cycle 2, using 2 different dosing schedules. The study design included an eltrombopag dose escalation phase starting at 75 mg daily to determine the optimal biological dose (OBD). Eighteen patients were enrolled and 15 received at least 1 dose of chemotherapy; 3 patients withdrew prior to receiving eltrombopag. Seven, 4, and 1 patients received 75 mg, 100 mg, and 150 mg eltrombopag daily, respectively. No dose-limiting toxicities were reported. Due to slow recruitment, the study was closed prior to identifying an OBD. The most common hematologic adverse events (AEs) were thrombocytopenia (80%), neutropenia (73%), and anemia (67%). The most common nonhematologic AEs were fatigue (53%), alanine aminotransferase increased, constipation, and nausea (47% each). Eleven of 12 patients who received eltrombopag completed at least 2 chemotherapy cycles; all had increased platelet counts on Day 1 of Cycle 2 (cycle with eltrombopag) compared to Day 1 of Cycle 1 (cycle without eltrombopag). Although data are limited, safety data were consistent with the known toxicities of AI combination chemotherapy or the side effect profile of eltrombopag seen in other studies. Available data suggest a potential pre- and post-chemotherapy dosing scheme for eltrombopag when administered with AI chemotherapy, and support further investigation of eltrombopag treatment in patients with chemotherapy-induced thrombocytopenia.
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影响因子：
50.5
作者：
Ang, J. E.;Shah, R. N.;Kaye, S. B.
通讯作者：
Kaye, S. B.
影响因子：
5.8
作者：
Sleijfer, S;Seynaeve, C;Verweij, J
通讯作者：
Verweij, J
影响因子：
45.3
作者：
Worden, FP;Taylor, JMG;Baker, LH
通讯作者：
Baker, LH
DOI：
10.1158/1078-0432.ccr-08-0336
发表时间：
2008-10-15
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Blay JY;von Mehren M;Samuels BL;Fanucchi MP;Ray-Coquard I;Buckley B;Gilles L;Lebedinsky C;Elsayed YA;Le Cesne A
通讯作者：
Le Cesne A
影响因子：
4.7
作者：
Hensley ML;Sill MW;Scribner DR Jr;Brown J;Debernardo RL;Hartenbach EM;McCourt CK;Bosscher JR;Gehrig PA
通讯作者：
Gehrig PA