改良XELOX方案治疗胃肠道腺癌伴肝转移的临床研究

Study on modified XELOX regimen for treatment of hepatic metastases from gastrointestinal cancer

目的探讨改良XELOX方案治疗胃肠道腺癌伴肝转移的有效性和安全性。方法回顾性分析2006年8月7日~2012年12月31日第二军医大学附属长海医院诊治的30例胃肠道腺癌伴肝转移患者的临床资料,所有均经病理活检、胃镜或结肠镜证实,未行原发灶切除术,且接受至少2个疗程的改良XELOX方案治疗。改良XELOX方案指将奥沙利铂50 mg灌注至原发灶,结直肠癌的系经肠系膜下动脉或者髂内动脉,胃癌系经胃左动脉或腹腔干,然后经肝动脉向肝内灌注50 mg奥沙利铂与适量的碘油混合进行化疗栓塞,最后留置导管于腹腔干或肝固有、肝左、肝右动脉缓慢（1 h）灌注100 mg奥沙利铂,第1天;1周后（或10 d后,具体情况根据患者血常规而定）服用卡培他滨,第8~21天,休息2~3周进行下一疗程,6个疗程后治疗间隔时间可适当延长至8~12周。每2个月通过CT和/或MRI检查肝内转移灶,胃镜、肠镜检查原发灶。随访其生存时间,按RECIST标准评价客观疗效。通过SPSS 19.0软件运用Kaplan-Meier法进行分析,对可能影响生存时间的因素进行Cox回归分析。结果 30例患者中位生存期12.0个月,95%CI 9.6~14.4,获完全缓解2例,部分缓解10例,疾病稳定8例,病变进展10例,总有效率为40.3%,中位无进展生存期为4.0个月,95%CI 2.2~5.8。治疗后不良反应主要为恶心、呕吐、疼痛、肝功能受损、骨髓抑制、外周感觉神经毒性等,多为Ⅰ~Ⅱ度,Ⅲ~Ⅳ度不良反应少见,经对症处治疗好转,无治疗相关性病死。其中23例发生恶心、呕吐,其次为肝功能异常（如ALT及AST升高）,但仅局限于肝动脉化疗栓塞治疗后3~5 d;骨髓抑制主要为白细胞、血小板减少。结论改良XELOX方案治疗胃肠道腺癌伴肝转移患者疗效确切,具有较高的客观有效率,能改善患者的生活质量,增加手术切除机会,不良反应可耐受。

Objective To explore the effectiveness, safety of modified XELOX for the treatment of hepatic metastases from gastrointestinal cancer. Methods From August 7th 2006 to December 31 st, 2012, in Changhai Hospital Affiliated to the Second Military Medical University, the clinical data of 30 patients with hepatic metastases from gastrointestinal cancer were retrospectively analyzed. All the patients were confirmed by biopsy pathologically, endoscopy or colonoscopy and received at least two courses of modified XELOX regimen. Modified XELOX meaned injecting 50 mg Oxaliplatin into the primary site of cancer, colorectal cancer was injected through mesenteric artery or Iliac artery and gastric was injected through left gastric artery or celiac trunk, then injecting certain lipiodol mixed oxaliplatin（50 mg） into hepatic artery with catheter for chemotherapy embolism, slowly（1 hour） pumping into Oxaliplatin 100 mg through indwell catheter in the hepatic artery or the left or right, at the 1st day; instructing patients taking capecitabine after one week（or almost 10 days, according to the specific circumstances of the patient＇s blood）, at the 8th-21 st day and after 3-5 weeks rest on to the next course of treatment. The treatment interval could be extended to 8-12 weeks after six courses. Liver metastases were examined by CT and/or MRI and primary tumor site by colonoscopy every 2 months. RECIST was used to evaluate the objective response. 19.0 SPSS software and Kaplan-Meier methods were applied. Cox regression model was used to analyze the possible factors about affection of the survival time. Results The median overall survival of the 30 patients was 12.0 months, 95% CI9.6-14.4, 2 cases were CR, 10 cases were PR, 8 cases were SD, 10 cases were PD, the efficiency was 40.3 %. The median progression-free survival was 4.0 months, 95%CI2.2-5.8. The adverse reactions after the treatment included nausea, vomiting, pain, impaired liver function, myelosuppression, peripheral sensory neuropathy and so on, most of which presented as grade Ⅰ-Ⅱ. All the adverse reactions disappeared after symptomatic treatment and there was no treatment-related death. There were 23 cases occurred nausea and vomiting. The second was liver function abnormalities, such as elevations of ALT and AST, but only lasted 3-5days after TACE; bone marrow mainly presented as white blood cells and platelets decreased. Conclusion Modified XELOX regimen is an effective treatment for hepatic metastases from gastric and colorectal cancer. It has high objective response rate, can commendably improve the quality of life of patients, increase opportunities for surgical resection and adverse reactions can be tolerated.