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

Clin Cancer Res. 2020 Jul 15;26(14):3537-3545. doi: 10.1158/1078-0432.CCR-20-0008. Epub 2020 Apr 22.

Abstract

Purpose: 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.

Patients and methods: 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 vice versa. 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.

Results: In total, 24 evaluable patients were included. In the tumor, CPC634 exhibited a 461% higher total docetaxel (P < 0.001) and a comparable released docetaxel concentration (P = 0.43). Plasma AUCinf was 27% higher (P = 0.001) and C max was 91% lower (P < 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; P < 0.001).

Conclusions: 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 C 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.

Publication types

  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Biopsy
  • Cross-Over Studies
  • Docetaxel / administration & dosage
  • Docetaxel / adverse effects
  • Docetaxel / analogs & derivatives
  • Docetaxel / pharmacokinetics*
  • Drug Carriers / chemistry*
  • Drug Liberation
  • Female
  • Humans
  • Infusions, Intravenous
  • Male
  • Middle Aged
  • Nanoparticles / chemistry*
  • Neoplasms / drug therapy*
  • Neoplasms / pathology
  • Neutropenia / blood
  • Neutropenia / chemically induced
  • Neutropenia / diagnosis
  • Neutropenia / epidemiology*
  • Response Evaluation Criteria in Solid Tumors
  • Tissue Distribution

Substances

  • Drug Carriers
  • Docetaxel