Association of intratumoral pharmacokinetics of fluorouracil with clinical response

Lancet. 1994 May 14;343(8907):1184-7. doi: 10.1016/s0140-6736(94)92399-x.

Abstract

In-vivo fluorine-19 nuclear magnetic resonance spectroscopy (NMRS) allows non-invasive, real-time, chemical identification of specific fluorinated compounds inside human tumours after administration of fluorouracil (5-fluorouracil). Kinetic measures of the administered drug and metabolites allow estimation of the tumoral half-life of fluorouracil. We studied 57 patients by 19F NMRS immediately after they had received 600 mg/m2 fluorouracil intravenously. Serial spectra were acquired with the surface coil positioned on the skin above the tumour. We defined an intratumoral half-life of fluorouracil of 20 min or more as indicating trapping of the drug, based on the blood half-life of 8-12 min. 19 patients had intratumoral half-lives indicating trapping of fluorouracil, 27 had half-lives less than 20 min, and 11 had no detectable fluorouracil in their tumours. 8 of 9 evaluable patients whose tumours showed trapping had partial responses to chemotherapy that included fluorouracil compared with only 2 of 25 patients whose tumours did not trap the drug (p = 0.000021). 19F NMRS can identify patients likely to respond to chemotherapy with fluorouracil and could be used clinically to tailor optimum treatment.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Fluorouracil / pharmacokinetics*
  • Fluorouracil / therapeutic use
  • Half-Life
  • Humans
  • Magnetic Resonance Spectroscopy*
  • Neoplasms / drug therapy
  • Neoplasms / metabolism*
  • Treatment Outcome

Substances

  • Fluorouracil