Difluorodeoxyuridine plasma concentrations after low-dose gemcitabine during chemoradiation in head and neck cancer patients.
OBJECTIVE
The aim of this study was to investigate whether relevant plasma levels of dFdU could be detected during concurrent chemoradiation (CRT) with low doses of dFdC administered in patients with head and neck cancer and to assess the toxicity related to dose.


METHODS
dFdC was administered at doses of 5 mg/m² twice weekly or 10, 50, or 100 mg/m² weekly. Plasma concentrations of dFdU were determined daily for 7 days after the first administration and before each administration, thereafter. A high-performance liquid chromatographic method was used. During CRT, skin and mucosal toxicity were scored weekly according to the RTOG toxicity scoring system.


RESULTS
Eight patients were sampled at the 10-50 mg/m² dose and nine at the 5-100 mg/m² dose. dFdU levels were in the micromolar range, inducing RS in vitro. There was a strong correlation between the area under the curve of dFdU and the dose of dFdC (r = 0.803, P < 0.001) and a weak correlation between trough concentrations and total dose of dFdC (r = 0.408, P = 0.017). Duration of severe mucositis correlated with dFdC dose.


CONCLUSIONS
During CRT with 10-100 mg/m(2) of dFdC weekly or 5 mg/m(2) twice weekly, dFdU remains detectable at potentially radiosensitizing concentrations.
Specenier
P
P
Medical Oncology, Antwerp University Hospital, Wilrijkstraat 10, 2650 Edegem, Belgium. Pol.specenier@uza.be
Guetens
G
G
Dyck
J
J
De Boeck
G
G
Weyler
J
J
Van den Weyngaert
D
D
Aelbrecht
K
K
Vermorken
J B
JB
D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage* / Q000009:adverse effects / Q000378:metabolism; D003131:Combined Modality Therapy; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D005467:Floxuridine / Q000031:analogs & derivatives* / Q000097:blood; D006258:Head and Neck Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000532:radiotherapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011838:Radiation-Sensitizing Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000378:metabolism; D000093542:Gemcitabine
D000964:Antimetabolites, Antineoplastic; D011838:Radiation-Sensitizing Agents; D005467:Floxuridine; D003841:Deoxycytidine; C084565:2',2'-difluoro-2'-deoxyuridine; D000093542:Gemcitabine