Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, the Netherlands.
Department of Radiology and Nuclear Medicine, Erasmus MC, University Medical Center, Rotterdam, the Netherlands.
Clin Cancer Res. 2020 Jul 15;26(14):3537-3545. doi: 10.1158/1078-0432.CCR-20-0008. Epub 2020 Apr 22.
CPC634 is a novel nanoparticle entrapping docetaxel, developed to enhance the intratumoral chemotherapy exposure. This randomized cross-over study compared the intratumoral and plasma pharmacokinetics of CPC634 with conventional docetaxel.
Adult patients with solid tumors were randomized to receive CPC634 (75 mg/m) in cycle 1, and conventional docetaxel (75 mg/m) in cycle 2 or . The study was powered to identify a 25% increase of intratumoral total docetaxel exposure after CPC634 infusion compared with conventional docetaxel. Four patients were allocated per tumor sampling time point, that is, 24, 48, 72, and 96 hours, 7 and 14 days after infusion during both cycles. Total docetaxel and released docetaxel from the nanoparticle were determined in tumor tissue derived from a metastatic lesion and in plasma. Pharmacokinetic data were analyzed using linear mixed modeling.
In total, 24 evaluable patients were included. In the tumor, CPC634 exhibited a 461% higher total docetaxel ( < 0.001) and a comparable released docetaxel concentration ( = 0.43). Plasma AUC was 27% higher ( = 0.001) and was 91% lower ( < 0.001) for CPC634 released docetaxel. The median observed neutrophil count nadir after conventional docetaxel treatment was lower (0.50 × 10/L) compared with CPC634 (4.30 × 10/L; < 0.001).
Here, we demonstrated that CPC634 enhanced the intratumoral total docetaxel exposure compared with conventional docetaxel. The lower incidence of neutropenia during CPC634 treatment is presumably related to lower plasma of released docetaxel. The unique pharmacokinetic profile of CPC634 nanoparticles has the potential to improve docetaxel treatment. A phase II efficacy trial of CPC634 is currently ongoing.
CPC634 是一种新型的载紫杉醇纳米颗粒，旨在提高肿瘤内化疗药物的暴露。本随机交叉研究比较了 CPC634 与常规紫杉醇的肿瘤内和血浆药代动力学。
成年实体瘤患者被随机分为第 1 周期接受 CPC634（75mg/m），第 2 周期接受常规紫杉醇（75mg/m）。该研究旨在确定与常规紫杉醇相比，CPC634 输注后肿瘤内总紫杉醇暴露增加 25%。每个肿瘤取样时间点分配 4 例患者，即输注后 24、48、72 和 96 小时，以及第 1 和第 2 周期的第 7 和第 14 天。从转移性病变获得的肿瘤组织和血浆中测定总紫杉醇和纳米颗粒释放的紫杉醇。使用线性混合模型分析药代动力学数据。
共纳入 24 例可评估患者。在肿瘤中，CPC634 的总紫杉醇（<0.001）和释放的紫杉醇浓度（=0.43）分别高出 461%和 461%。CPC634 释放的紫杉醇的血浆 AUC 高出 27%（=0.001），而 低 91%（<0.001）。常规紫杉醇治疗后观察到的中性粒细胞计数最低值（0.50×10/L）低于 CPC634（4.30×10/L；<0.001）。
在这里，我们证明与常规紫杉醇相比，CPC634 提高了肿瘤内总紫杉醇的暴露。CPC634 治疗期间中性粒细胞减少的发生率较低，可能与释放的紫杉醇血浆浓度较低有关。CPC634 纳米颗粒的独特药代动力学特征有可能改善紫杉醇治疗。目前正在进行 CPC634 的 II 期疗效试验。
