Combined therapy of locally advanced rectal adenocarcinoma with capecitabine and concurrent radiotherapy

Abstract

3720 Background: Concomitant chemoradiotherapy with capecitabine could improve outcome in: patients with locoregionally advanced undisseminated rectal cancer. Methods: Since X/2001 to V/2003 capecitabine and concurrent radiotherapy was applied in locally advanced rectal cancer (cT3–4, and/or N+, M0). 43 patients, 31 men, 12 women, median age 59. Capecitabine 825 mg/m2 twice a daily was given concomitantly with pelvic radiotherapy 1,8 Gy daily up to 45 Gy followed by a boost up to 50,4 Gy. Results: Pathological complete response in 9(21%) pts, minimal microscopic residuum in 7(16%) pts and together 37% pts. with a substantial remission were diagnosed. Thymidylate synthase (TS), thymidine phosphorylase (TP), dihydropyrimidine dehydrogenase (DPD) and TNFα mRNA/GAPDH mRNA relative levels from tumor and adjacent tissue has been measured by means of Real Time PCR. Before treatment TS mRNA median was higher in tumors (1.7x) than in adjacent mucosa. Changes in mRNA levels in the course of therapy were different in tumor and adjacent non affected mucosa. TS mRNA median level in tumors increased 1,3x in the course of therapy, but median in adjacent mucosa increased 2,3x. Tumor TS mRNA median in the course of therapy was 1.5x higher in responders (pT0,N0 or pR1,N0) than in non responders. Tumor TP mRNA median levels increased 3.09x in all pts, but only 2.63x in patients with remission. There was an 2.56x increase of mucosal TP mRNA in total, but negligible (1.004x) in patients with remissions in the course of therapy. Median tumor DPD mRNA level of non responders is 3.9x higher than in responders before therapy or 3.5x higher in the course of therapy respectively. Tumor TNFα mRNA median level is increased 2.8x in responders but 4.32x in non responders. Conclusions: The concurrent chemoradiotherapy proved to be effective for treatment of locally advanced rectal cancer. The analysis shows the increased level of TS mRNA in tumor tissue and elevation of TP mRNA in tumor during radiotherapy in all pts. But the evaluated markes of fluoropyrimidine metabolism don't correlate with therapeutic response. No significant financial relationships to disclose.