title: F10 Inhibits Growth of PC3 Xenografts and Enhances the Effects of Radiation Therapy.
abstract: Chemotherapy remains of limited use for the treatment of prostate cancer with only one drug, docetaxel, demonstrating a modest survival advantage for treatment of late-stage disease. Data from the NCI 60 cell line screen indicated that the castration-resistant prostate cancer cell lines PC3 and DU145 were more sensitive than average to the novel polymeric fluoropyrimidine (FP), F10, despite displaying less than average sensitivity to the widely-used FP, 5FU. Here, we show that F10 treatment of PC3 xenografts results in a significant survival advantage (treatment to control ratio (T/C) days = 18; p < 0.001; n = 16) relative to control mice treated with saline. F10 (40 mg/kg/dose) was administered via jugular vein catheterization 3-times per week for five weeks. This aggressive dosing regimen was completed with no drug-induced weight loss and with no evidence of toxicity. F10 was also shown to sensitize PC3 cells to radiation and F10 was also shown to be a potent radiosensitizer of PC3 xenograftsin vivowith F10 in combination with radiation resulting in significantly greater regression of PC3 xenografts than radiation alone. The results indicate that F10 in this pre-clinical setting is an effective chemotherapeutic agent and possesses significant radiosensitizing properties.
authors.affiliation: Department of Cancer Biology, Wake Forest University School of Medicine, USA.
authors.forename: William H
authors.initials: WH
authors.lastname: Gmeiner
authors.affiliation: Department of Pathology, Wake Forest University School of Medicine, USA.
authors.forename: Mark C
authors.initials: MC
authors.lastname: Willingham
authors.affiliation: Department of Radiation Oncology, Wake Forest University School of Medicine, USA.
authors.forename: J Daniel
authors.initials: JD
authors.lastname: Bourland
authors.affiliation: Department of Cancer Biology, Wake Forest University School of Medicine, USA.
authors.forename: Heather C
authors.initials: HC
authors.lastname: Hatcher
authors.affiliation: Department of Orthopedics, Wake Forest University School of Medicine, USA.
authors.forename: Thomas L
authors.initials: TL
authors.lastname: Smith
authors.affiliation: Department of Public Health Sciences, Wake Forest University School of Medicine, USA.
authors.forename: Ralph B
authors.initials: RB
authors.lastname: D'Agostino
authors.affiliation: Department of Radiation Oncology, Wake Forest University School of Medicine, USA.
authors.forename: William
authors.initials: W
authors.lastname: Blackstock
keywords: Fluoropyrimidine; Prostate cancer; Radiosensitization; Thymidylate synthase