1575P - 5-Fluorouracil (5FU) intratumoural pharmacokinetics: Rapid uptake in cells and in spheroids (SPH)

Date 10 October 2016
Event ESMO 2016 Congress
Session Poster display
Topics Translational Research
Presenter Maria Jove
Citation Annals of Oncology (2016) 27 (6): 526-544. 10.1093/annonc/mdw392
Authors M. Jove1, P. Loadman2, J. Wicks2, J. Spencer2, A. Race2, R. Salazar3, C.J. Twelves4
  • 1Medical Oncology, The Leeds Teaching Hospital NHS Trust St. James University Hospital, LS9 7TF - Leeds/GB
  • 2Drug And Metabolism Pharmacokinetics, Institute Cancer Therapeutics, BD7 1DP - Bradford/GB
  • 3Medical Oncology, Catalan Institute of Oncology, 08907 - L´Hospitalet/ES
  • 4Medical Oncology, Leeds Institute of Cancer & Pathology, Leeds ECMC, LS9 7TF - Leeds/GB

Abstract

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

Conclusions

Our 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 identification

Not applicable

Legal entity responsible for the study

Institute Cancer Therapeutics (Bradford University) / University of Leeds

Funding

Institute Cancer Therapeutics Spanish Medical Oncology Society

Disclosure

All authors have declared no conflicts of interest.