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

RESUMEN

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ABSTRACT

Background and purpose. To investigate the presenceof 5-Fluorouracil (5-FU) in pelvic tissue afteroral administration of tegafur. To measure tegafurand 5-FU concentrations in normal rectal mucosa,perirectal fat and residual tumor in rectal cancerpatients receiving preoperative chemoradiation. Tocorrelate drug concentrations with cancer downstagingeffects.Patients and methods. Three tissue samples takenfrom 16 surgical specimens after recto-sigmoid resectionwere analyzed. Tegafur and 5-FU concentrationswere measured using high-performance liquidchromatography. 16 patients with locallyadvanced rectal cancer were treated with preoperativepelvic irradiation (45-50 Gy) sensitized withoral tegafur (400 mg for every 8 hours daily). Sevenpatients received a precharge dose of tegafur (400mg oral every 8 hours) 24 hours before surgery.Results. In 8 of the 9 patients who did not receive aprecharge dose, detectable levels of tegafur wereobserved in fat tissue, normal mucosa and tumor,but detectable 5-FU levels were only observed inone patient. Mean concentrations (ranges) for tegafurin fat, normal mucosa and tumor in patientswithout 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 thesame samples were 0.95, 1.92 and 2.68 ng/g (1 patient),respectively.In patients receiving a tegafur precharge, both tegafurand 5-FU were present in all tissue sampleswith the exception of 2 fat samples, in which drugconcentrations were undetectable.5-FU levels were higher in tumor than other sites,with a median value of 68.24 ng/g (range 3.8-283.05ng/g). Tegafur levels were also higher in tumorsamples than other sites (mean 3446.53 ng/g, range1044.5-7847.0 ng/g), except in 2 patients who hadhigher levels of tegafur in normal mucosa.Conclusions. Tegafur and 5-FU are not always presentin pelvic tissues 5 to 6 weeks after oral administrationof tegafur. Both drugs were present in thetissues analyzed, in relevant concentrations, 24hours after oral administration of tegafur. The dataobtained suggest a tendency (not significant) towarda correlation between levels of 5-FU presentin the residual tumor and cancer downstaging