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Hyaluronic acid–paclitaxel: effects of intraperitoneal administration against CD44(+) human ovarian cancer xenografts

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Abstract

Purpose

Hyaluronan (HA)-receptors (mainly CD44 and RHAMM) are overexpressed in a wide variety of cancers including ovarian tumors, and HA-bioconjugates have been developed to enhance selective entry of cytotoxic drugs into HA receptor-expressing cancerous cells. Here, we evaluated the potential application of a new HA-paclitaxel bioconjugate, ONCOFID-P, for intraperitoneal (IP) treatment of ovarian cancer.

Methods

In vitro cytotoxic effect of ONCOFID-P was first assessed on CD44(+) OVCAR-3 and SKOV-3 human ovarian cancer cell lines. Studies were performed in female Balb/c athymic mice IP implanted with OVCAR-3 or SKOV-3 and treated with IP ONCOFID-P, and IP and intravenous (IV) free paclitaxel, at their maximum tolerated dose (MTD 168, 80 and 80 mg/kg, total dose, respectively). The potential detrimental effect of the IP ONCOFID-P and IP free paclitaxel on hematopoiesis was also assessed on peripheral blood, bone marrow and spleen.

Results

Results show that ONCOFID-P cytotoxicity against both OVCAR-3 and SKOV-3 cell lines was somewhat less effective than free paclitaxel. Conversely, in in vivo experiments, IP treatment with ONCOFID-P was overall more effective than IV and IP free paclitaxel in inhibiting intra-abdominal tumor dissemination, abrogating ascites, prolonging survival and curing mice. ONCOFID-P and IP free paclitaxel were equivalent in terms of myelotoxicity, although the former was administered at a two-fold higher dose.

Conclusions

Present data strongly support the development of ONCOFID-P for locoregional treatment of ovarian cancer.

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Conflict of interest

This work has been supported by a grant from Fidia Farmaceutici, Abano Terme, Italy. The funding sources had no role in the study design, data collection, data analysis, data interpretation, and writing of this report or in the decision to submit the paper for publication.

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Authors and Affiliations

  1. Department of Obstetrics and Gynaecology, Catholic University of the Sacred Heart, Largo A. Gemelli, 8, 00168, Rome, Italy

    Ilaria De Stefano, Alessandra Battaglia, Maria Grazia Prisco, Andrea Fattorossi, Daniele Travaglia, Giovanni Scambia, Cristiano Ferlini & Daniela Gallo

  2. Department of Histopathology, Catholic University of the Sacred Heart, Largo A. Gemelli, 8, 00168, Rome, Italy

    Gian Franco Zannoni

  3. Institute of Clinical Biochemistry, Catholic University of the Sacred Heart, Largo A. Gemelli, 8, 00168, Rome, Italy

    Silvia Baroni

  4. Fidia Farmaceutici S.p.A, Via Ponte della Fabbrica 3/A, 35031, Abano Terme (PD) Padova, Italy

    Davide Renier

Authors
  1. Ilaria De Stefano
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  10. Cristiano Ferlini
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Correspondence to Daniela Gallo.

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De Stefano, I., Battaglia, A., Zannoni, G.F. et al. Hyaluronic acid–paclitaxel: effects of intraperitoneal administration against CD44(+) human ovarian cancer xenografts. Cancer Chemother Pharmacol 68, 107–116 (2011). https://doi.org/10.1007/s00280-010-1462-2

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  • DOI: https://doi.org/10.1007/s00280-010-1462-2

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