부산대학교 도서관

The purpose of the study was to determine the maximum-tolerated dose (MTD) of oral capecitabine, combined with concurrent, standard preoperative pelvic radiotherapy, when given twice daily, from Monday to Friday throughout the course of radiotherapy, for locally advanced potentially resectable rectal cancer. Maximum-tolerated dose was defined as the total (given in two equally divided doses) oral dose of capecitabine that caused treatment-related grade 3 or 4 toxicity in one-third or more of the patients treated. Radiotherapy involved 50.4?Gy given in 28 fractions in 5 weeks and 3 days. Eligible patients had a newly diagnosed clinical stage T3-4 N0-2 M0 rectal adenocarcinoma located within 12?cm of the anal verge suitable for curative resection. Surgery was performed 4-6 weeks from completion of preoperative chemoradiotherapy. In all, 28 patients were enrolled in the study at predefined dose levels: 850?mg?m-2?day-1 (n=3), 1000?mg?m-2?day-1 (n=6), 1250?mg?m-2?day-1 (n=3), 1650?mg?m-2?day-1 (n=3), 1800?mg?m-2?day-1 (n=8) and 2000?mg?m-2?day-1 (n=5). The mean age was 62.3 years (range: 33-80 years). Five patients were female and 23 male. The median distance of tumour from the anal verge was 6?cm (range: 1-11?cm). Endorectal ultrasound was performed in 93%of patients. A total of 26 patients (93%) had T3 disease and two patients had resectable T4 disease. Dose-limiting toxicity (DLT) developed in one patient at dose level 1000?mg?m-2?day-1 (RTOG grade 3 cystitis). Two of the five patients at dose level 2000?mg?m-2?day-1 had a total of three DLT (grade 3 perineal skin reaction, grade 3 diarrhoea and grade 3 dehydration). Dose escalation of capecitabine was ceased at 2000?mg?m-2?day-1 after reaching MTD. None of the eight patients at dose level 1800?mg?m-2?day-1 developed DLT. All except one patient underwent surgery. A total of 15 patients had the clinical T stage reduced by at least one stage in pathologic specimens. Five patients (19%) achieved a pathologic complete response. We conclude that the MTD of capecitabine was reached at a dose level of 2000?mg?m-2?day-1, given as 1000?mg?m-2 twice daily, from Monday to Friday throughout the course of preoperative pelvic irradiation of 50.4?Gy. For patients with resectable rectal cancer receiving concurrent, full dose radiotherapy, the recommended dose of capecitabine for further study is 1800?mg?m-2?day-1 when given in this schedule.British Journal of Cancer (2004) 91, 1019-1024. doi:10.1038/sj.bjc.6602106 www.bjcancer.com Published online 10 August 2004 [ABSTRACT FROM AUTHOR]