局部晚期直肠癌新辅助调强放化疗后腹腔镜手术Ⅰ期研究

Preoperative intensity-modulated radiotherapy(IMRT) with oral capecitabine followed by laparoscopic total mesorectal excision(LTME) for locally advanced rectal cancer:a phase Ⅰ trial

目的评估局部晚期直肠癌新辅助调强放化疗后腹腔镜手术的安全性及有效性。方法选择24例病理确诊Ⅱ～Ⅲ期的直肠腺癌患者，原发病灶及转移淋巴结外放1cm予放疗，剂量55Gy，每次2．2Gy，盆腔放疗剂量为45Gy，每次18Gy。卡培他滨化疗按每日500、750、1000、1250、1650、1800及2000mg／m。共7个剂量梯度（每个梯度3例）爬坡进行，于放疗d1—14及d22—35口服。观察患者的剂量限制性毒性。放化疗后6～8周内行腹腔镜下直肠癌全系膜切除术。结果在卡培他滨第1至第4剂量梯度未见剂量限制性毒性出现。在第5剂量梯度组中1例出现3级腹泻，新人组3例患者无剂量限制性毒性发生。在第6剂量梯度，2例患者分别出现3级腹泻和3级放射性皮炎，故第5梯度卡培他滨剂量[1650mg／（m^2·d）]被推荐为进一步研究使用剂量。24例患者手术均达R0切除，5例（20．8％）到达病理完全缓解。术后出现会阴部感染及肠梗阻各1例，术后30d无死亡病例。结论直肠癌新辅助调强放化疗后腹腔镜手术治疗安全有效，推荐新辅助治疗中卡培他滨剂量为1650mg／（m^2·d）。

Objective TO assess the safety and feasibility of preoperative intensity-modulated radiotherapy （IMRT） with oral capecitabine followed by laparoscopic total mesorectal excision （LTME） for locally advanced rectal cancer. Methods Twenty four patients with histologically confirmed stages Ⅱ-Ⅲ rectal adenocarcinoma were enrolled in the study. IMRT was delivered with a dose of 55 Gy（2.2Gy/d for 5 w） to the primary tumor sites plus 1 cm out of metastatic lymph nodes; IMRT was simultaneously delivered with a dose of 45Gy （1.8 Gy/d for 5 w） to the regional lymph nodes and areas at risk for harboring microscopic disease. Capecitabine was given twice daily from d1- d14 and d22 - d35 during radiotherapy. Dose levels of capecitabine were gradually escalated with 7 gradients （3 cases in each gradient）： 500, 750, 1 000, 1 250, 1 650, 1 800 and 2 000mg/ （m2od）. The dose-limiting toxicity （DLT） was observed in patients. LTME was scheduled 6-8 w after termination of chemoradiotherapy. Results On dose level 1 to level 4, no dose-limiting toxicities occurred; 1 patients experienced grade 3 diarrhea on dose level 5. Among the additional 3 patients no one developed DLT. Of 3 patients treated on dose level 6, 2 exhibited DLT （diarrhea in 1 and radiation dermatitis in 1）. Therefore, dose level 5 （1 650mg/m2/d） was determined as the recommended dose for future studies. All patients underwent surgery and 24 patients reached the R0 resection. Five patients （20.8%） had a pathologically complete re- mission（PCR）. Postoperative complications included one pelvic wound infection and one ileus. There were no deaths in the first 30 d postoperatively. Conclusion Preoperative IMRT with oral capecitabine and laparoscopic surgery is safe and feasible for patients with locally advanced rectal cancer. Recommended dosage of capecitabine for future trials is 1 650mg/m2/d.