局部晚期直肠癌术前含草酸铂同步放化疗Ⅱ期临床研究

A phaseⅡstudy of preoperative concurrent chemoradiotherapy of oraliplatin containing regimen for locally advanced rectal cancer

目的评价术前同步放疗与草酸铂和氟尿嘧啶(5-FU)或甲酰四氢叶酸钙(CF)联合化疗治疗局部晚期直肠癌的耐受性和有效性。方法58例初诊局部晚期直肠癌(T3～T4期)患者进入该研究,疗前获病理类型,腺癌54例,印戒细胞癌4例。放疗为3个野等中心技术,盆腔照射46 Gy分23次4.5周完成。在放疗第1周和第4周同步给予2个周期化疗,草酸铂130 mg/m^2第1天,5-FU 500 mg/m^2第1～3天和CF 200 mg/m^2第1～3天。放疗结束后4～6周进行手术。结果完成术前计划并行手术者55例,手术标本总有效率为58%,其中肿瘤全消(pCR)11例,仅检出少量残存肿瘤细胞21例。3级毒副反应包括中性粒细胞减少1例,腹泻3例,放射性直肠炎4例,肝功能异常1例。结论含草酸铂方案的术前联合放化疗耐受性良好,有效率高,应进一步随访并开展Ⅲ期临床试验,以明确对局部控制率和生存率的影响。

Objective To evaluate the tolerance and efficacy of preoperative concurrent chemoradiotherapy with oxaliplatin and 5-flurouracil/folinic acid （5-FU/CF） for locally advanced rectal cancer. Methods From February 2002 to November 2005, 58 locally advanced rectal cancer untreated patients （T3- T4） were allotted into this study. Including 54 adenocarcinoma and 4 signet-ring cell carcinoma. Pelvic radiotherapy was delivered with a three-field technique to a total dose of 46 Gy over 4.5 weeks. Two cycles of chemotherapy were given concurrently on week 1 and 4, with oxaliplatin 130 mg/m^2 on day 1 and folinic acid 200 mg/m^2 followed by 5-flurouracil 500 mg/m^2 on day 1 to 3. Surgery was carried out 4 to 6 weeks later. Results All patients completed the neo-adjuvant treatment without any modification, and surgery was perormed in 55 patients. An objective clinical response was seen in 32（58% ） of 55 patients, including 11 （20%） achieving pathological complete response（pCR） and, in 21（38% ）, only a few residual cells were detected. Grade 3 toxicity was seen in 8 patients. No postoperative death and grade 4 toxicity wasa observed. Conclusions Preoperative concurrent chemoradiotherapy, using oxaliplatin-containing regimen, is well tolerated and has a high response rate in locally advanced rectal cancer without increasing the surgical toxicity. These patients are to be followed and a phase Ⅲ clinical trial should be carry out to evaluate its effects on local control and survival.