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

• Verfasst von: Schlemmer, Heinz-Peter [VerfasserIn]
• Verfasst von: Bachert, Peter [VerfasserIn]
• Verfasst von: Rudat, Volker [VerfasserIn]
• Verfasst von: Vanselow, Bernhard [VerfasserIn]
• Verfasst von: Knopp, Michael V. [VerfasserIn]
• Verfasst von: Weidauer, Hagen [VerfasserIn]
• Verfasst von: Wannenmacher, Michael [VerfasserIn]
• Verfasst von: Kaick, Gerhard van [VerfasserIn]
• Titel: Alterations of intratumoral pharmacokinetics of 5-fluorouracil in head and neck carcinoma during simultaneous radiochemotherapy
• Verf.angabe: Heinz-Peter Schlemmer, Markus Becker, Peter Bachert, Andreas Dietz, Volker Rudat, Bernhard Vanselow, Petra Wollensack, Iwan Zuna, Michael V. Knopp, Hagen Weidauer, Michael Wannenmacher, and Gerhard van Kaick
• E-Jahr: 1999
• Jahr: May 15, 1999
• Umfang: 7 S.
• Fussnoten: Gesehen am 17.02.2021
• Titel Quelle: Enthalten in: Cancer research
• Ort Quelle: Philadelphia, Pa. : AACR, 1916
• Jahr Quelle: 1999
• Band/Heft Quelle: 59(1999), 10, Seite 2363-2369
• ISSN Quelle: 1538-7445
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1748495712

Abstract

The kinetics of local drug uptake and metabolism of the anticancer drug 5-fluorouracil (5-FU) has been monitored by means of 19F nuclear magnetic resonance spectroscopy in 17 patients with neck tumors during concurrent radiochemotherapy. All of the patients underwent an accelerated hyperfractionated, concomitant-boost radiochemotherapy with 5-FU [600 or 1000 mg/m2 of body surface (b.s.)] and carboplatin (70 mg/m2 of b.s.). Serial 19F nuclear magnetic resonance spectra were obtained during and after the administration 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 performed at day 1 of therapy and, in 13 patients, also after 43.5 Gy of irradiation at day 1 of the second chemotherapy cycle. Resonances of 5-FU and the catabolites 5,6-dihydro-5-fluorouracil (DHFU) and α-fluoro-β-alanine (FBAL) were resolved in the tumor spectra. The median of the 5-FU and FBAL levels was significantly higher (more than 2-fold) at the second compared with the first examination, whereas the level of DHFU did not change. This effect could indicate an increased delivery of 5-FU into the interstitial space 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 mechanism for synergy between radio- and chemotherapy is discussed, but alternative mechanisms are also being considered. The findings indicate that a method is available to rationally address the design of dosing schedules in concurrent therapy regimens.