Intratumoral Comparison of Nanoparticle Entrapped Docetaxel (CPC634) with Conventional Docetaxel in Patients with Solid Tumors.

Abstract

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/m²) in cycle 1, and conventional docetaxel (75 mg/m²) in cycle 2 or <i>vice versa</i>. 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 (<i>P</i> < 0.001) and a comparable released docetaxel concentration (<i>P</i> = 0.43). Plasma AUC_inf was 27% higher (<i>P</i> = 0.001) and <i>C</i> _max was 91% lower (<i>P</i> < 0.001) for CPC634 released docetaxel. The median observed neutrophil count nadir after conventional docetaxel treatment was lower (0.50 × 10⁹/L) compared with CPC634 (4.30 × 10⁹/L; <i>P</i> < 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 <i>C</i> _max 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.