Abstract 2498
Background
Limited data are available on 5FU intratumoral pharmacokinetics. Previous studies with radiolabeled 5FU showed homogeneous uptake in spheroids within a few minutes (Cancer Chemother Pharmacol. 1984;13(2):131-5) but no quantification was done. We present data on intracellular and intra-spheroidal 5FU uptake; drug efflux experiments are on-going and results will be presented.
Methods
MCF-7 and HCT-116 cells were used for cellular and spheroid experiments. Spheroid growth was optimized to produce a spheroid of 300-400 µm diameter at day 4. Treatment: 1x106 cells or 30 spheroids/time point were exposed to 10 µM (1300ng/mL) 5FU at
Results
Both MCF-7 and HCT-116 achieved steady state by 20min in cells (1800ng/g aprox.) and 60min in spheroids (330ng/g aprox.) that was maintained at 240min. No 5FUrd was seen but 5FdUrd was identified in the HCT-116 cell line; with 5FdUrd included, total drug levels at steady state were 3000ng/g and 1000ng/g in cells and spheroids, respectively. Although there was variability in the HCT-116 drug levels between experiments, the contour of the drug uptake curve was consistent. MCF-7 spheroids are being analyzed.
5FU uptake ng/g Mean [range]
| Min | HCT-116 cells | MCF-7 cells | HCT-116 spheroids |
|---|---|---|---|
ConclusionsOur results suggest that 5FU is rapidly taken up into cells and spheroids, being less prominent in spheroids. These data and methodology may be useful to allow generation of mathematical models to improve drug delivery. Clinical trial identificationNot applicable Legal entity responsible for the studyInstitute Cancer Therapeutics (Bradford University) / University of Leeds FundingInstitute Cancer Therapeutics Spanish Medical Oncology Society DisclosureAll authors have declared no conflicts of interest. Resources from the same sessionZUMA-3: A phase 1/2 multi-center study evaluation the safety and efficacy of KTE-C19 anti-CD19 CAR T cells in adult patients with relapsed/refractory B precursor acute lymphoblastic leukemia (R/R ALL)Presenter: Bijal Shah Session: Poster display Resources: Abstract ZUMA-2: A phase 2 multi-center study evaluating the efficacy of KTE-C19 (Anti-CD19 CAR T cells) in patients with relapsed/refractory Mantle cell lymphoma (R/R MCL)Presenter: Michael Wang Session: Poster Display Resources: Abstract ZUMA-1: A phase 2 multi-center study evaluating anti-CD19 chimeric antigen receptor (CAR) T cells in patients with refractory aggressive non-Hodgkin lymphoma (NHL)Presenter: Sattva Neelapu Session: Poster Display Resources: Abstract Younger age as a prognostic indicator in breast cancer: Correlation between clinical-pathologic factors and miRNAs and long-term follow-upPresenter: Maria Teresa Martinez Session: Poster display Resources: Abstract Window study of the PARP inhibitor rucaparib in patients with primary triple negative or BRCA1/2 related breast cancer (RIO)Presenter: Christy Toms Session: Poster display Resources: Abstract Whole exome sequencing (WES) and RNA sequencing (RNA-seq) in routine clinical practice for colorectal cancer (CRC) and non-small cell lung cancer (NSCLC) patients (pts)Presenter: Géraldine Perkins Session: Poster display Resources: Abstract What is the optimal annual interpretive volume for a radiologist reading screening mammograms?Presenter: Asli Uluturk Session: Poster display Resources: Abstract What decides breast conservation versus mastectomy in the background of diverse sociocultural environment, an Indian studyPresenter: Poonamalle Padmanabhan Bapsy Session: Poster display Resources: Abstract Waiting time to diagnosis and treatment of the head and neck cancer in four institutions in PortugalPresenter: Ana Castro Session: Poster display Resources: Abstract Wait times for diagnosis and treatment of lung cancer: a single centre experiencePresenter: Catherine Labbe Session: Poster Display Resources: Abstract This site uses cookies. Some of these cookies are essential, while others help us improve your experience by providing insights into how the site is being used. For more detailed information on the cookies we use, please check our Privacy Policy.
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