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

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/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.

RESULTS

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).

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 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.