Ⅱ期和(或)Ⅲ期直肠癌术后希罗达同步放化疗的研究

Phase Ⅰ study of postoperative concurrent chemoradiation with capecitabine as adjuvant treatment for stage Ⅱ / Ⅲ operable rectal cancer

目的探讨Ⅱ期和(或)Ⅲ期直肠癌患者根治术后,采用希罗达同步放化疗的剂量限制性毒性反应(DLT)和最大耐受剂量(MTD)。方法24例直肠癌患者,年龄为18-75岁,KPS评分≥70分, 根治性手术后病理证实为Ⅱ期和(或)Ⅲ期。希罗达从放射治疗第1天开始服用,间隔12 h,连续服用14 d,休息7 d,为1个周期。共治疗2个周期。同步进行的盆腔放射治疗5周,共25次,总剂量为 50 Gy。≥3度的血液学或非血液学毒性反应为希罗达DLT。结果24例患者分别入希罗达每天 1000 mg／m2组(3例)、1200 mg／m2组(3例)、1400 mg／m2组(3例)、1500 mg/m2组(3例)、1600 mg／m2 组(6例)和1700 mg／m2组(6例)。1600 mg／m2组出现1例DLT(1例3度腹泻),补充3例后,未出现DLT,继而进入每天1700 mg／m2组。1700 mg／m2组相继出现2例DLT(3度和4度腹泻各1例)。结论Ⅱ期和(或)Ⅲ期直肠癌根治术后希罗达同步放化疗是安全、可行的。希罗达的最大耐受剂量为每天1600 mg／m2,限制性毒性反应为腹泻。

Objective This phase Ⅰ study is to determine the maximal tolerated dose and the doselimiting toxicity of capecitabine combined with standard radiotherapy （RT） as postoperative adjuvant treatment for rectal cancer patients. Methods Stage Ⅱ/Ⅲ rectal cancer patients 18-75 years of age had undergone curative surgery with Karnofsky score ≥70% were eligible to be included in this study. Total dose of RT DT 50 Gy was delivered to the pelvic area in fraction of 2.0 Gy per day for 5 weeks. Capecitabine was orally administered concurrently with radiotherapy for a total of 2 cycles in escalating doses： twice daily at 12 hour interval for consecutive 14 days as one cycle, separated by a seven day rest, then followed by another cycle. From March 2004 to May 2005, 24 patients were included and treated at the following dose levels： daily 1000 mg/m^2 （3 patients）, 1200 mg/m^2 （3 patients）, 1400 mg/m^2 （3 patients）, 1500 mg/m^2 （3 patients）, 1600 mg/m^2 （6 patients）, and 1700 mg/m^2 （6 patients）. Dose-limiting toxicities （DLT） including grade 3 or grade 4 hematologic and nonhematologic toxicity were observed. Results Dose-limiting toxicity was observed in one patient treated at dose of 1600 mg/m^2 with grade 3 diarrhea, and in 2 patients at dose of 1700 mg/m^2 with one grade 3 and one grade 4 diarrhea. Conclusion Diarrhea is the most common dose-limiting toxicity. In our study, the maximal tolerated dose （ MTD ） of capecitabine given concurrently with radiotherapy was daily 1600 mg/m^2, from D1 to D14 separated by 7-day rest for 2 cycles. Capecitabine given concurrently with standard radiotherapy is safe and tolerable for operated stage Ⅱ/Ⅲ rectal cancer patients.