Chemoradiotherapy with 5-fluorouracil/leucovorin, surgery and adjuvant chemotherapy for locally advanced rectal cancer

Abstract

Abstract. the aim of this study was to demonstrate a pathologic complete response (pcr) rate of at least 10% with an acceptable toxicity achieved by preoperative chemoradiotherapy with 5-fluorouracil (5-FU)/leucovorin in patients with locally advanced rectal cancer. Patients were treated by radiotherapy targeting 50 Gy and 5-FU/leucovorin intravenously during the 1st, 4th and 7th week after start of radiotherapy followed by surgery and adjuvant chemotherapy. In 71 evaluable patients, the pcr rate was 14.1% (95% cI, 6.0-22.2); the local relapse rate, 6.1%; the 5-year disease-free survival, 54% and the overall 5-year survival, 68%. the most severe adverse events were neutropenia (17%), diarrhoea (17%), infection (8%) and fatal cardiovascular function (1%). this therapy yielded a high rate of pcr, a low rate of local relapse and a long disease-free and overall survival. to increase its feasibility, radiation dose reduction to 45 gy and administration of only two preoperative cycles of chemotherapy is recommended. IntroductionIn the 1990s adjuvant 5-fluorouracil (5-FU)-based chemotherapy combined with radiotherapy in patients with stage II and III rectal cancer after surgical resection was established as the new standard of care decreasing the rate of local recurrence and improving patient survival (1,2). A significant change in the treatment of rectal cancer occurred with the introduction of total mesorectal excision (tMe) resulting in decreased local recurrences and improved survival (3). In 1995, when this trial started, preoperative therapy was applied to downstage tumors in order to increase sphincter-sparing surgery in distal rectal tumors and to decrease the overall toxicity.We conducted a single centre phase II trial in order to investigate the feasibility and outcome of 5-FU-based preoperative chemotherapy combined with long-term irradiation followed by surgical treatment including tMe, followed by postoperative 5-FU-based chemotherapy. The results, after a median follow-up of approximately three years (38.9 months; range 2.8-108.2 months), are presented and discussed within the context of the results published in the literature. Patients and methodsPatients were enrolled between november 1995 and november 2004. eligibility criteria included histopathologically confirmed adenocarcinoma of the rectum [according to the 1987 International Union Against Cancer (UICC) staging system] within 15 cm of the anal verge. the clinical tnM stage was assessed by clinical examination, rigid proctoscopy, endorectal ultrasonography, computed tomography scanning and nuclear magnetic resonance of the abdomen and pelvis. Patients with t3, t4 and with distal t2 (<4 cm from the anal verge) rectal cancers, respectively, were included irrespective of their nodal status. Patients with a single hepatic or lung metastasis were eligible. Patients were required to have a leukocyte level >3.0x109 /l and a thrombocyte level >100x10 9 /l, normal liver function with bilirubin values <2 mg/ dl and normal renal function with creatinine value...