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Cancer Chemother Pharmacol (2011) 68:107116
DOI 10.1007/s00280-010-1462-2
ORIGINAL ARTICLE
Hyaluronic acidpaclitaxel: eVects of intraperitoneal administration against CD44(+) human ovarian cancer xenografts
Ilaria De Stefano Alessandra Battaglia Gian Franco Zannoni Maria Grazia Prisco Andrea Fattorossi Daniele Travaglia Silvia Baroni Davide Renier
Giovanni Scambia Cristiano Ferlini Daniela Gallo
Received: 1 July 2010 / Accepted: 2 September 2010 / Published online: 17 September 2010 Springer-Verlag 2010
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 eVect of ONCOFID-P was
Wrst 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 eVect 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 eVective than free paclitaxel. Conversely, in in vivo experiments, IP treatment with ONCOFID-P was overall more eVective 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.
Keywords Hyaluronan Paclitaxel CD44 Mice Ovarian cancer
Introduction
Epithelial ovarian cancer is the leading cause of death for gynecological cancer in most of the Western world. It is the ninth most common cancer and the Wfth leading cause of cancer death among women in the United States [1]; in European women, it accounts for 41,900 cases (about 3.9% of all female cancers) [2]. Ovarian cancer is recognized to be one of the most chemotherapy-sensitive malignancies, with 7080% of newly diagnosed patients being anticipated to exhibit a...