PMID- 10344745
OWN - NLM
STAT- MEDLINE
DCOM- 19990617
LR  - 20151119
IS  - 0008-5472 (Print)
IS  - 0008-5472 (Linking)
VI  - 59
IP  - 10
DP  - 1999 May 15
TI  - Alterations of intratumoral pharmacokinetics of 5-fluorouracil in head and neck 
      carcinoma during simultaneous radiochemotherapy.
PG  - 2363-9
AB  - 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 15-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 alpha-fluoro-beta-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.
FAU - Schlemmer, H P
AU  - Schlemmer HP
AD  - Research Program Radiological Diagnostics and Therapy, German Cancer Research 
      Center (Deutsches Krebsforschungszentrum), University of Heidelberg. 
      h.schlemmer@dkfz-heidelberg.de
FAU - Becker, M
AU  - Becker M
FAU - Bachert, P
AU  - Bachert P
FAU - Dietz, A
AU  - Dietz A
FAU - Rudat, V
AU  - Rudat V
FAU - Vanselow, B
AU  - Vanselow B
FAU - Wollensack, P
AU  - Wollensack P
FAU - Zuna, I
AU  - Zuna I
FAU - Knopp, M V
AU  - Knopp MV
FAU - Weidauer, H
AU  - Weidauer H
FAU - Wannenmacher, M
AU  - Wannenmacher M
FAU - van Kaick, G
AU  - van Kaick G
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Cancer Res
JT  - Cancer research
JID - 2984705R
RN  - 0 (Antimetabolites, Antineoplastic)
RN  - 0 (Isotopes)
RN  - 11P2JDE17B (beta-Alanine)
RN  - 284SYP0193 (Fluorine)
RN  - 3821-81-6 (alpha-fluoro-beta-alanine)
RN  - 696-06-0 (5-fluorodihydrouracil)
RN  - BG3F62OND5 (Carboplatin)
RN  - U3P01618RT (Fluorouracil)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Antimetabolites, Antineoplastic/administration & dosage/*pharmacokinetics
MH  - Antineoplastic Combined Chemotherapy Protocols/therapeutic use
MH  - Biotransformation
MH  - Carboplatin/administration & dosage
MH  - Carcinoma, Squamous Cell/drug therapy/*metabolism/pathology/radiotherapy
MH  - Combined Modality Therapy
MH  - Drug Administration Schedule
MH  - Female
MH  - Fluorine
MH  - Fluorouracil/administration & dosage/analogs & 
      derivatives/analysis/*pharmacokinetics
MH  - Head and Neck Neoplasms/drug therapy/*metabolism/pathology/radiotherapy
MH  - Humans
MH  - Isotopes
MH  - Lymphatic Metastasis
MH  - Magnetic Resonance Imaging
MH  - Male
MH  - Middle Aged
MH  - beta-Alanine/analogs & derivatives/analysis
EDAT- 1999/05/27 00:00
MHDA- 1999/05/27 00:01
CRDT- 1999/05/27 00:00
PHST- 1999/05/27 00:00 [pubmed]
PHST- 1999/05/27 00:01 [medline]
PHST- 1999/05/27 00:00 [entrez]
PST - ppublish
SO  - Cancer Res. 1999 May 15;59(10):2363-9.