Authors' Affiliations: Royal Marsden Hospital, London;
AstraZeneca, Macclesfield; and.
Clin Cancer Res. 2014 Jul 1;20(13):3603-12. doi: 10.1158/1078-0432.CCR-13-1881. Epub 2014 Apr 8.
Cediranib is a potent VEGF signaling inhibitor with activity against all three VEGF receptors and KIT. This phase II study evaluated the antitumor activity of cediranib in patients with metastatic gastrointestinal stromal tumor (GIST) resistant/intolerant to imatinib, or metastatic soft-tissue sarcomas (STS; ClinicalTrials.gov, NCT00385203).
Patients received cediranib 45 mg/day. Primary objective was to determine the antitumor activity of cediranib according to changes in 2[18F]fluoro-2-deoxy-D-glucose positron emission tomography ((18)FDG-PET) tumor uptake in patients with GIST using maximum standardized uptake values (SUVmax). Secondary objectives included objective tumor response and tolerability in patients with GIST/STS.
Thirty-four of 36 enrolled patients were treated (GIST n = 24; STS n = 10). At day 29, five patients had confirmed decreases in SUVmax (≥10% from day 8) and two had confirmed partial metabolic responses (≥25% decrease), but arithmetic mean percentage changes in SUVmax, averaged across the cohort, were not significant at day 8 [6.8%; 95% confidence interval (CI), 19.95-33.54) or day 29 (4.6%; 95% CI, 8.05-17.34). Eleven patients with GIST achieved a best objective tumor response of stable disease; eight achieved stable disease ≥16 weeks. In patients with STS, four of six with alveolar soft-part sarcoma (ASPS) achieved confirmed and durable partial responses. The commonest adverse events were diarrhea (85%), fatigue (74%), and hypertension (68%).
In patients progressing on imatinib/sunitinib, cediranib 45 mg/day demonstrated evidence of activity by (18)FDG-PET, but did not reduce average SUVmax. Evidence of antitumor activity was seen in ASPS.
西地尼布是一种强效的 VEGF 信号抑制剂，对所有三种 VEGF 受体和 KIT 均有活性。这项 II 期研究评估了 Cediranib 在对伊马替尼耐药/不耐受的转移性胃肠道间质瘤（GIST）或转移性软组织肉瘤（STS）患者中的抗肿瘤活性（ClinicalTrials.gov，NCT00385203）。
患者每天接受 Cediranib 45mg。主要目的是根据 GIST 患者 2[18F]氟-2-脱氧-D-葡萄糖正电子发射断层扫描（18FDG-PET）肿瘤摄取的最大标准化摄取值（SUVmax）变化，确定 Cediranib 的抗肿瘤活性。次要目标包括 GIST/STS 患者的客观肿瘤反应和耐受性。
36 名入组患者中有 34 名接受了治疗（GIST n=24；STS n=10）。在第 29 天，有 5 名患者 SUVmax 确有下降（较第 8 天下降≥10%），2 名患者确有部分代谢缓解（下降≥25%），但 SUVmax 的平均算术百分比变化，在第 8 天[6.8%；95%置信区间（CI），19.95-33.54]和第 29 天[4.6%；95%CI，8.05-17.34]均无显著意义。11 名 GIST 患者获得最佳客观肿瘤缓解，病情稳定；8 名患者病情稳定≥16 周。在 STS 患者中，6 名腺泡软组织肉瘤（ASPS）患者中有 4 名确有持久的部分缓解。最常见的不良反应是腹泻（85%）、疲劳（74%）和高血压（68%）。
在伊马替尼/舒尼替尼进展的患者中，西地尼布 45mg/天通过 18FDG-PET 显示出活性证据，但未降低 SUVmax 的平均值。在 ASPS 中观察到抗肿瘤活性的证据。
