| Title | Increasing tumoral 5-fluorouracil concentrations during a 5-day continuous infusion: a microdialysis study |
|---|---|
| Published in | Cancer Chemotherapy and Pharmacology, Vol. 67, No. 5, p.1055-1062. ISSN 0344-5704. |
| Author | Konings, I.R.H.M. (Inge); Sleijfer, S. (Stefan); Matthijsen, R.H.J. (Ron); Bruijn, de P. (Peter); Ghobadi Moghadam-Helmantel, I.M. (Inge); Dam, van L.M. (Linda); Wiemer, E.A.C. (Erik); Verweij, J. (Jaap); Loos, W.J. (Walter) |
| Date | 2010-01-01 |
| Language | English |
| Type | article |
| Abstract | Purpose: Response to anticancer therapy is believed to be directly related to the concentration of the anticancer drug in the tumor itself. Assessment of intra-tumor drug pharmacokinetics can be helpful to gain more insight into mechanisms involved in the (in)sensitivity of tumors to anticancer therapy. We explored the pharmacokinetics of 5-fluorouracil in both plasma and tumor tissue during a 5-day continuous infusion of 5-fluorouracil in patients with cancer. Sampling for measurement of 5-fluorouracil in tumor tissue was performed using microdialysis. Experimental design: In seven patients with an accessible (sub)cutaneous tumor treated with a continuous 5-fluorouracil infusion, plasma and microdialysate samples from tumor and normal adipose tissue were collected over a period of 5 days. Results: For six patients, drug concentrations in both tumor tissue and plasma were available. Concentration-time curves of unbound 5-fluorouracil were lower in tumor tissue compared to the curves in plasma, but exposure ratios of tumor tissue versus plasma increased during the 5-day infusion period. The presence of circadian rhythmicity of 5-fluorouracil pharmacokinetics in the tumor itself was demonstrated as 5-fluorouracil concentrations in tumor extracellular fluid were higher during the night than during daytime. Conclusion: Microdialysis was successfully employed in patients with cancer during a continuous 5-day 5-fluorouracil infusion. Plasma and tumor pharmacokinetics of 5-fluorouracil differed substantially with increasing 5-fluorouracil concentrations in tumor over time, possibly resulting from a lowered interstitial fluid pressure by 5-fluorouracil itself. This microdialysis 5-fluorouracil model might be useful to monitor the effect of drug delivery modulating strategies in future studies. |
| Publication | http://hdl.handle.net/1765/20201 |
| Persistent Identifier | urn:NBN:nl:ui:15-1765/20201 |
| Metadata | XML |
| Repository | Erasmus University Rotterdam |
Go to page top
Go back to contents
Go back to site navigation