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

Autor: Atrafi F; Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, the Netherlands., van Eerden RAG; Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, the Netherlands., van Hylckama Vlieg MAM; Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, the Netherlands., Oomen-de Hoop E; Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, the Netherlands., de Bruijn P; Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, the Netherlands., Lolkema MP; Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, the Netherlands., Moelker A; Department of Radiology and Nuclear Medicine, Erasmus MC, University Medical Center, Rotterdam, the Netherlands., Rijcken CJ; Cristal Therapeutics, Maastricht, the Netherlands., Hanssen R; Cristal Therapeutics, Maastricht, the Netherlands., Sparreboom A; Division of Pharmaceutics and Pharmaceutical Chemistry, College of Pharmacy, The Ohio State University, Columbus, Ohio., Eskens FALM; Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, the Netherlands., Mathijssen RHJ; Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, the Netherlands., Koolen SLW; Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, the Netherlands. s.koolen@erasmusmc.nl.; Department of Hospital Pharmacy, Erasmus MC, Rotterdam, the Netherlands.
Jazyk: angličtina
Zdroj: Clinical cancer research : an official journal of the American Association for Cancer Research [Clin Cancer Res] 2020 Jul 15; Vol. 26 (14), pp. 3537-3545. Date of Electronic Publication: 2020 Apr 22.
DOI: 10.1158/1078-0432.CCR-20-0008
Abstrakt: 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 2 ) in cycle 1, and conventional docetaxel (75 mg/m 2 ) 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 AUC inf 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 × 10 9 /L) compared with CPC634 (4.30 × 10 9 /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.
(©2020 American Association for Cancer Research.)
Databáze: MEDLINE
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