Research Papers:

Polymeric nanoparticle-docetaxel for the treatment of advanced solid tumors: phase I clinical trial and preclinical data from an orthotopic pancreatic cancer model

Si Yeol Song, Kyu-pyo Kim, Seong-Yun Jeong, Jin Park, Jaesook Park, Joohee Jung, Hye Kyung Chung, Sa-Won Lee, Min Hyo Seo, Jung-shin Lee, Kyung Hae Jung and Eun Kyung Choi _

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Oncotarget. 2016; 7:77348-77357. https://doi.org/10.18632/oncotarget.12668

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Si Yeol Song1,3, Kyu-pyo Kim2, Seong-Yun Jeong3,4, Jin Park3,4, Jaesook Park3,4, Joohee Jung5, Hye Kyung Chung6, Sa-Won Lee7, Min Hyo Seo7, Jung-shin Lee2,3, Kyung Hae Jung2, Eun Kyung Choi1,3

1Department of Radiation Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea

2Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea

3Institute for Innovative Cancer Research, Asan Medical Center, Seoul, Korea

4Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea

5College of Pharmacy, Duksung Women’s University, Seoul, Korea

6Korea Institute of Radiological and Medical Sciences, National Project to Establish Platform to Develop The New Concept Therapy, Seoul, Korea

7Department of Parenteral Delivery Program, Samyang Pharmaceuticals R&D, Daejeon, Korea

Correspondence to:

Eun Kyung Choi, email: [email protected]

Kyung Hae Jung, email: [email protected]

Keywords: PNP-DTX, phase I, MTD, efficacy, pancreas

Received: March 27, 2016    Accepted: September 25, 2016    Published: October 14, 2016


We assessed the efficacy of the polymeric nanoparticle containing docetaxel (PNP-DTX) in preclinical mouse models and determined the maximum tolerated dose (MTD) through clinical study. Subcutaneous and orthotopic mouse models were dedicated. Tumor growth delay in orthotopic model and quantification of in vivo imaging in orthotopic model were evaluated. Phase I clinical study was a single-center, prospective, open-label trial in advanced solid tumors. PNP-DTX was injected intravenously and the starting dose was 20 mg/m2 escalated to 35 mg/m2, 45 mg/m2, 60 mg/m2 and 75 mg/m2. Pharmacokinetics, tumor response, toxicities were evaluated. Preclinical result revealed the more potent cytotoxic effect of PNP-DTX than docetaxel (DTX). However, there was no difference between PNP-DTX and DTX in subcutaneous model. Tubulin polymerization assay showed that PNP-DTX preserved original mode of action of DTX. For phase I clinical trial, 18 patients were analyzed. The dose of 75 mg/m2 was tentatively determined as the MTD and the most common toxicity was grade 4 neutropenia not lasting over 7days. The Cmax of 60 mg/m2 PNP-DTX and AUClast of 45 mg/m2 PNP-DTX were measured to be comparable to those of 75 mg/m2 DTX. Partial remission (PR) was achieved in 4 (22%) patients. The potency of PNP-DTX was revealed especially in orthotopic mouse model. The MTD of PNP-DTX could not be confirmed, but 75 mg/m2 was tentatively determined. The PNP-DTX of 45 mg/m2 had the same pharmacokinetic profile with that of 75 mg/m2 DTX.

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