Annals of Surgical Oncology

, Volume 20, Issue 5, pp 1684–1693

Cytoreductive Surgery and Intraoperative Administration of Paclitaxel-loaded Expansile Nanoparticles Delay Tumor Recurrence in Ovarian Carcinoma

Authors

    • Division of Thoracic Surgery, Department of SurgeryBrigham and Women’s Hospital
  • Morgan Schulz
    • Division of Thoracic Surgery, Department of SurgeryBrigham and Women’s Hospital
  • Rong Liu
    • Division of Thoracic Surgery, Department of SurgeryBrigham and Women’s Hospital
  • Kimberly Ann V. Zubris
    • Departments of Biomedical Engineering and ChemistryBoston University
  • Robert F. Padera
    • Department of PathologyBrigham and Women’s Hospital
  • Paul J. Catalano
    • Department of Biostatistics and Computational BiologyDana-Farber Cancer Institute
  • Mark W. Grinstaff
    • Departments of Biomedical Engineering and ChemistryBoston University
  • Yolonda L. Colson
    • Division of Thoracic Surgery, Department of SurgeryBrigham and Women’s Hospital
Gynecologic Oncology

DOI: 10.1245/s10434-012-2696-5

Cite this article as:
Gilmore, D., Schulz, M., Liu, R. et al. Ann Surg Oncol (2013) 20: 1684. doi:10.1245/s10434-012-2696-5

ABSTRACT

Background

Locoregional recurrence significantly impacts survival and quality of life in patients with ovarian carcinoma. We hypothesize that local administration of paclitaxel-loaded expansile nanoparticles (pax-eNP) at the time of cytoreductive surgery decreases local tumor recurrence.

Methods

In vitro cytotoxicity of pax-eNP was assessed against both the OVCAR-3 human ovarian cancer cell line and tumor cells isolated from a malignant pleural effusion from a patient with multidrug-resistant ovarian cancer. A murine xenogenic model involving surgical cytoreduction of established OVCAR-3 intra-abdominal tumor was used to evaluate in vivo efficacy of intraoperative intraperitoneal (IP) injection of 10 mg/kg of paclitaxel either as pax-eNP or paclitaxel in Cremophor EL/ethanol solution (pax-C/E) versus empty eNP controls. Cytoreductive surgery and intraoperative treatment were performed 4 weeks after established tumor. All animals were sacrificed when empty eNP controls displayed extensive evidence of disease progression.

Results

Labeled-eNP entered tumor cells in vitro within 4 h and specifically accumulated at sites of tumor in vivo. Pax-eNP exhibited dose-dependent cytotoxicity in both OVCAR-3 and patient tumor cells isolated from a malignant pleural effusion and effectively prevented tumor recurrence following debulking (p = 0.003 vs. empty eNP). Furthermore, pax-eNP-treated animals did not develop severe recurrent carcinomatosis compared with 43 % of the pax-C/E-treated cohort, suggesting that single-dose intracavitary pax-eNP is more effective than an equivalent dose of pax-C/E.

Conclusions

Expansile nanoparticles readily enter human ovarian tumor cells and localize to sites of tumor in vivo with pax-eNP cytotoxicity resulting in superior inhibition of locoregional tumor recurrence following cytoreductive surgery.

Supplementary material

10434_2012_2696_MOESM1_ESM.doc (762 kb)
Supplementary material 1 (DOC 761 kb)

Copyright information

© Society of Surgical Oncology 2012