Université de Lyon, Service d'oncologie médicale, Centre d'Investigation des Thérapeutiques en Oncologie et Hématologie, Centre Hospitalier Lyon-Sud, Pierre Benite 69495, France.
Br J Cancer. 2012 Aug 7;107(4):598-603. doi: 10.1038/bjc.2012.304. Epub 2012 Jul 12.
This phase I cohort study investigated aflibercept (vascular endothelial growth factor (VEGF) trap) plus docetaxel and cisplatin in patients with advanced solid tumours.
Patients received intravenous aflibercept 4, 5, or 6 mg kg(-1) with docetaxel and cisplatin (75 mg m(-2) each) on day 1 of a 3-week cycle until progressive disease or unacceptable toxicity. Primary objectives were determining cycle 1 dose-limiting toxicities (DLTs) and the aflibercept recommended phase II trial dose (RP2D) for this combination.
During the dose-escalation phase (n=16), there were two DLTs of febrile neutropenia (at 4 and 5 mg kg(-1)). Granulocyte colony-stimulating factor prophylaxis was subsequently recommended. The RP2D of aflibercept was established at 6 mg kg(-1) and administered to 14 additional patients. The most frequent grade 3/4 adverse events (AEs) were neutropenia (43.3%), stomatitis (20.0%), asthenia/fatigue (20.0%), and hypertension (16.7%). All-grade AEs associated with VEGF blockade included epistaxis (83.3%), dysphonia (70.0%), proteinuria (53.3%), and hypertension (50.0%). There were five partial responses (16.7%) and 18 cases of stable disease (60.0%) (lasting >3 months in 10 patients). There were no pharmacokinetic (PK) interactions between the three drugs.
Aflibercept 6 mg kg(-1) with docetaxel and cisplatin 75 mg m(-2) every 3 weeks is the RP2D based on tolerability, antitumour activity, and PKs.
这项 I 期队列研究调查了阿柏西普（血管内皮生长因子（VEGF）陷阱）联合多西他赛和顺铂治疗晚期实体瘤患者的效果。
患者在每 3 周的周期中，接受静脉注射阿柏西普 4、5 或 6mg/kg，联合多西他赛和顺铂（各 75mg/m²），直到疾病进展或无法耐受毒性。主要目标是确定第 1 周期的剂量限制毒性（DLT）和这种联合治疗的阿柏西普推荐的 II 期试验剂量（RP2D）。
在剂量递增阶段（n=16），有两例发热性中性粒细胞减少症（4mg/kg 和 5mg/kg）为 DLT。随后建议使用粒细胞集落刺激因子预防。阿柏西普的 RP2D 确定为 6mg/kg，并在另外 14 名患者中使用。最常见的 3/4 级不良事件（AE）为中性粒细胞减少症（43.3%）、口腔炎（20.0%）、乏力/疲劳（20.0%）和高血压（16.7%）。所有级别的与 VEGF 阻断相关的 AE 包括鼻出血（83.3%）、声音嘶哑（70.0%）、蛋白尿（53.3%）和高血压（50.0%）。有 5 例部分缓解（16.7%）和 18 例疾病稳定（60.0%）（10 例患者的持续时间超过 3 个月）。三种药物之间没有药代动力学（PK）相互作用。
基于耐受性、抗肿瘤活性和 PK，阿柏西普 6mg/kg 联合多西他赛和顺铂 75mg/m² 每 3 周一次是 RP2D。
