Thymidine phosphorylase to dihydropyrimidine dehydrogenase ratio as a predictive factor of response to preoperative chemoradiation with capecitabine in patients with advanced rectal cancer.
OBJECTIVE
To identify if thymidine phosphorylase (TP), dihydropyrimidine dehydrogenase (DPD), and ratio TP/DPD levels in tumor tissues are potential predictive factors for response to combined preoperative chemoradiation with capecitabine, in patients with locally advanced rectal cancer (LARC).


METHODS
Between 2004 and 2006, 28 patients with LARC (cT2-T4, N0-N2) were treated with neoadjuvant chemoradiation. Total radiation dose was 50.4 Gy and daily dose was 1.8 Gy in 5.5 weeks. Capecitabine was administrated 1,650 mg/m(2)/day, 7 days/week. Preoperative staging was based on combined computer tomography and endorectal ultrasound. Tissue samples, both neoplastic and normal ones, were endoscopically taken before treatment for TP and DPD measurement with ELISA. Levels of total proteins were calculated by the Bradford method.


RESULTS
Median TP, DPD, ratio TP/DPD levels in the primary tumors were 32.85 U/mg, 18.73 U/mg, and 1.64 respectively. Median ratio TP/DPD of patients with proven pathological "response" (downstaging of the disease) was higher than the "no response" group, 4.40 and 1.42, respectively (P = 0.0001). Levels of TP and DPD in tumor tissue did not reveal any statistically important difference between the two groups.


CONCLUSIONS
TP/DPD ratio is a possible predictive factor for tumor response after concomitant preoperative chemoradiation with capecitabine in LARC.
Boskos
C S
CS
1st Radiation Oncology Department, Agios Savvas Anticancer Institute, Athens, Greece. docboss2001@hotmail.com
Liacos
C
C
Korkolis
D
D
Aygerinos
K
K
Lamproglou
I
I
Terpos
E
E
Stoupa
E
E
Baltatzis
G
G
Beroukas
K
K
Papasavvas
P
P
Dimopoulos
M A
MA
Bamias
A
A
D000230:Adenocarcinoma / Q000188:drug therapy / Q000201:enzymology / Q000473:pathology / Q000532:radiotherapy; D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D000069287:Capecitabine; D017024:Chemotherapy, Adjuvant; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D042943:Dihydrouracil Dehydrogenase (NADP) / Q000378:metabolism*; D005260:Female; D005472:Fluorouracil / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011300:Preoperative Care; D011829:Radiation Dosage; D018714:Radiotherapy, Adjuvant; D012004:Rectal Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology / Q000532:radiotherapy*; D013939:Thymidine Phosphorylase / Q000378:metabolism*; D016896:Treatment Outcome; D055815:Young Adult
D000964:Antimetabolites, Antineoplastic; D003841:Deoxycytidine; D000069287:Capecitabine; D042943:Dihydrouracil Dehydrogenase (NADP); D013939:Thymidine Phosphorylase; D005472:Fluorouracil