Alterations of intratumoral pharmacokinetics of 5-fluorouracil in head andneck carcinoma during simultaneous radiochemotherapy

The kinetics of local drug uptake and metabolism of the anticancer drug 5-f luorouracil (5-FU) has been monitored by means of F-19 nuclear magnetic res onance spectroscopy in 17 patients with neck tumors during concurrent radio chemotherapy, All of the patients underwent an accelerated hyperfractionate d, concomitant-boost radiochemotherapy with 5-FU [600 or 1000 mg/m(2) of bo dy surface (b.s.)] and carboplatin (70 mg/m(2) of b.s.), Serial F-19 nuclea r magnetic resonance spectra were obtained during and after the administrat ion of 5-FU in a 1.5-T scanner with the use of a 5-cm diameter surface coil positioned on a cervical lymph node metastasis. Examinations were performe d at day 1 of therapy and, in 13 patients, also after 43.5 Gy of irradiatio n at day 1 of the second chemotherapy cycle. Resonances of 5-FU and the cat abolites 5,6-dihydro-5-fluorouracil (DHFU) and alpha-fluoro-beta-alanine (F BAL) were resolved in the tumor spectra, The median of the 5-FU and FBAL le vels was significantly higher (more than 2-fold) at the second compared wit h the first examination, whereas the level of DHFU did not change. This eff ect could indicate an increased delivery of 5-FU into the interstitial spac e of the tumor in the course of the combined treatment, which would result in an enhanced exposure of the tumor cells to the drug. A potential mechani sm for synergy between radio- and chemotherapy is discussed, but alternativ e mechanisms are also being considered. The findings indicate that a method is available to rationally address the design of dosing schedules in concu rrent therapy regimens.