Tegafur and 5-fluorouracil pelvic tissue concentrations in rectal cancer patients receiving preoperative chemoradiation.

Abstract

BACKGROUND AND PURPOSE:

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.

PATIENTS AND 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.

• Authors: F A Calvo, A Aldaz, L Zufía, D de la Mata, J Serrano, R García, J A Arranz, A Alvarado, J Giráldez
• Journal: Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico (Clin Transl Oncol) Vol. 8 Issue 7 Pg. 500-7 (Jul 2006) ISSN: 1699-048X [Print] Italy
• PMID: 16870540 (Publication Type: Journal Article)

Chemical References

• Antimetabolites, Antineoplastic
• Tegafur
• Fluorouracil

Topics

• Adipose Tissue (metabolism)
• Adult
• Aged
• Antimetabolites, Antineoplastic (metabolism, therapeutic use)
• Female
• Fluorouracil (metabolism)
• Humans
• Intestinal Mucosa (metabolism)
• Male
• Middle Aged
• Neoplasm, Residual (metabolism)
• Pelvis
• Rectal Neoplasms (drug therapy, metabolism, radiotherapy)
• Rectum (metabolism)
• Tegafur (metabolism, therapeutic use)
• Treatment Outcome