A phase I dose escalation and pharmacodynamic study of SU5416 (semaxanib) combined with weekly cisplatin and irinotecan in patients with advanced solid tumors.

IF 0.3 4区 医学 Q4 Medicine
Onkologie Pub Date : 2013-01-01 Epub Date: 2013-10-14 DOI:10.1159/000355665
Ludmila K Martin, Tanios Bekaii-Saab, Derek Serna, Paul Monk, Steven K Clinton, Michael R Grever, Eric H Kraut
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引用次数: 5

Abstract

Background: This phase I study evaluated the safety of SU5416, a potent and selective inhibitor of the vascular endothelial growth factor (VEGF) receptor tyrosine kinase Flk-1, in combination with weekly cisplatin and irinotecan in patients with advanced solid tumors.

Methods: The patients received cisplatin 30 mg/m² and irinotecan 50 mg/m² weekly from week 1 to week 4, with SU5416 at either 65 mg/m² (dose level (DL)1) or 85 mg/m² (DL2) twice weekly for 6 weeks (1 cycle). Serial ¹⁸fluorodeoxyglucose-positron emission tomography (¹⁸FDG-PET) and ¹⁵O-H₂O-PET scans were obtained.

Results: 13 patients were treated (7 on DL1, 6 on DL2); 7 patients completed at least 1 cycle of treatment. 3 patients experienced dose-limiting toxicity (DLT) at DL2 (grade 3 neutropenia and grade 3 thrombocytopenia causing treatment delay, grade 3 nausea/vomiting). No objective responses were observed at DL1, which was determined to be the maximum tolerated dose (MTD). 1 partial response (PR) was observed at DL2. ¹⁸FDG-PET responses were documented but did not predict response according to the Response Evaluation Criteria in Solid Tumors (RECIST).

Conclusions: SU5416 at 65 mg/m² twice weekly combined with cisplatin and irinotecan weekly for 4 of 6 weeks is well tolerated but without evidence of clinical activity. ¹⁸FDG-PET may be a useful pharmacodynamic marker of SU5416 bioactivity but requires additional development.

SU5416 (semaxanib)联合每周顺铂和伊立替康治疗晚期实体瘤患者的I期剂量递增和药效学研究
背景:这项I期研究评估了SU5416的安全性,SU5416是一种有效的选择性血管内皮生长因子(VEGF)受体酪氨酸激酶Flk-1抑制剂,与每周顺铂和伊立替康联合用于晚期实体瘤患者。方法:患者从第1周至第4周接受顺铂30 mg/m²和伊立替康50 mg/m²,SU5416为65 mg/m²(剂量水平(DL)1)或85 mg/m²(DL2),每周2次,持续6周(1周期)。我们获得了一系列的¹⁸氟脱氧葡萄糖正电子发射断层扫描(¹⁸FDG-PET)和¹⁸O-H₂- pet扫描。结果:13例患者获得治疗(DL1 7例,DL2 6例);7例患者完成至少1个疗程的治疗。3例患者在DL2时出现剂量限制性毒性(3级中性粒细胞减少症和3级血小板减少症导致治疗延迟,3级恶心/呕吐)。在确定最大耐受剂量(MTD)为DL1时,未观察到客观反应。在DL2处观察到1个部分缓解(PR)。¹⁸我们记录了FDG-PET的反应,但根据实体瘤反应评估标准(RECIST)并不能预测反应。结论:SU5416剂量为65 mg/m²,每周2次,每周联合顺铂和伊立替康,持续4至6周,耐受性良好,但无临床活性证据。¹⁸FDG-PET可能是一种有用的SU5416生物活性药效学标记物,但需要进一步开发。
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来源期刊
Onkologie
Onkologie 医学-肿瘤学
CiteScore
0.40
自引率
33.30%
发文量
0
审稿时长
3 months
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