Tegafur and 5-fluorouracil pelvic tissue concentrations in rectal cancer patients receiving preoperative chemoradiation.
OBJECTIVE
To investigate the presence of 5-Fluorouracil (5-FU) in pelvic tissue after oral administration of tegafur. To measure tegafur and 5-FU concentrations in normal rectal mucosa, perirectal fat and residual tumor in rectal cancer patients receiving preoperative chemoradiation. To correlate drug concentrations with cancer downstaging effects.


METHODS
Three tissue samples taken from 16 surgical specimens after recto-sigmoid resection were analyzed. Tegafur and 5-FU concentrations were measured using high-performance liquid chromatography. 16 patients with locally advanced rectal cancer were treated with preoperative pelvic irradiation (45-50 Gy) sensitized with oral tegafur (400 mg for every 8 hours daily). Seven patients received a precharge dose of tegafur (400 mg oral every 8 hours) 24 hours before surgery.


RESULTS
In 8 of the 9 patients who did not receive a precharge dose, detectable levels of tegafur were observed in fat tissue, normal mucosa and tumor, but detectable 5-FU levels were only observed in one patient. Mean concentrations (ranges) for tegafur in fat, normal mucosa and tumor in patients without the precharge dose were 72.19 (12.1-205.6), 179.53 (11.30-727.7) and 252.35 (27.9-874.6) ng/g, respectively; mean concentrations for 5-FU in the same samples were 0.95, 1.92 and 2.68 ng/g (1 patient), respectively. In patients receiving a tegafur precharge, both tegafur and 5-FU were present in all tissue samples with the exception of 2 fat samples, in which drug concentrations were undetectable. 5-FU levels were higher in tumor than other sites, with a median value of 68.24 ng/g (range 3.8-283.05 ng/g). Tegafur levels were also higher in tumor samples than other sites (mean 3446.53 ng/g, range 1044.5-7847.0 ng/g), except in 2 patients who had higher levels of tegafur in normal mucosa.


CONCLUSIONS
Tegafur and 5-FU are not always present in pelvic tissues 5 to 6 weeks after oral administration of tegafur. Both drugs were present in the tissues analyzed, in relevant concentrations, 24 hours after oral administration of tegafur. The data obtained suggest a tendency (not significant) toward a correlation between levels of 5-FU present in the residual tumor and cancer downstaging.
Calvo
F A
FA
Department of Oncology, Hospital General Universitario Gregorio Marañón, Madrid, Spain. fcalvo.hgugm@salud.madrid.org
Aldaz
A
A
Zufía
L
L
de la Mata
D
D
Serrano
J
J
García
R
R
Arranz
J A
JA
Alvarado
A
A
Giráldez
J
J
D000273:Adipose Tissue / Q000378:metabolism; D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000378:metabolism* / Q000627:therapeutic use; D005260:Female; D005472:Fluorouracil / Q000378:metabolism*; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D018365:Neoplasm, Residual / Q000378:metabolism; D010388:Pelvis; D012004:Rectal Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000532:radiotherapy*; D012007:Rectum / Q000378:metabolism; D005641:Tegafur / Q000378:metabolism* / Q000627:therapeutic use; D016896:Treatment Outcome
D000964:Antimetabolites, Antineoplastic; D005641:Tegafur; D005472:Fluorouracil