表柔比星联合奥沙利铂和短期5-FU持续滴注的EOF5方案一线治疗晚期胃癌的疗效评估

背景与目的：晚期胃癌治疗中，ECF(表柔比星、顺铂及5-FU持续滴注21 d)方案系经典一线方案，2004年起我们以奥沙利铂取代顺铂，以低剂量5-FU持续滴注120 h取代标准剂量持续滴注21 d，组成EOF5方案，以期提高疗效及依从性，先后开展了小样本探索性研究及扩大样本的Ⅱ期研究。方法：本研究回顾性分析了该两项Ⅱ期研究结果。患者均接受了表柔比星50 mg/m2，静脉推注，第1天；奥沙利铂130 mg/m2，静脉滴注2 h，第1天；每天5-FU的剂量为375~425 mg/m2，低剂量持续输注5 d共120 h；每3周重复，每6周评价疗效。治疗到进展、不能耐受或患者退出，对于6~8个疗程后稳定以上疗效的患者根据医师推荐及患者的意愿，选择氟尿嘧啶类药物维持治疗或观察。结果：178例晚期胃癌患者纳入本研究，170例可行疗效及不良反应评估，7例(3.9%)完全缓解(complete response，CR)，76例(42.7%)部分缓解(partial response，PR)，总有效率(overall response rate，ORR，CR+PR)为46.6%，69例(38.8%)疾病稳定(stable disease，SD)，18例(10.1%)疾病进展(progressive disease，PD)。中位无进展生存期(progress free survival，PFS)为6.0个月(95%CI：5.2~6.8)，中位总生存期(overall survival，OS)为12.6个月(95%CI：8.9~16.3)，1、2年生存率分别为50.9%和28.0%。3~4度以上不良反应主要有白细胞及中性粒细胞减少23.0%及38.8%、血红蛋白下降6.5%、血小板下降23.5%、恶心呕吐14.1%、手足麻木1.2%。接受二线治疗的75例患者，二线治疗中位生存时间8.0个月(95%CI：4.8~11.2)。结论：EOF5方案治疗晚期胃癌有效率高，PFS和OS同ECF及其改良方案类似，不良反应可控，是安全有效的晚期胃癌一线治疗方案。

The clinical evaluation of EOF5 regimen,the combination of epirubicin,oxaliplatin and 5-day continuous infusion of 5-FU,for patients with advanced/metastatic gastric cancer

Background and purpose: Although there is still no standard first line chemotherapy regimen for metastatic gastric cancer (MGC), the doublet and triplet regimens containing platinum and fluorouracil were most popular worldwidely. The ECF regimen is the classical and one of the most popular treatment choices in this setting, while the marrow suppression, the renal toxicity and poor compliance inhibits its usage. In order to improve its efficacy and tolerability, this study conducted 2 phase Ⅱ trials by modified ECF regimen, the EOF5 regimen (substituting cisplatin with oxaliplatin, shortening the continuous infusion period to 120 h), to treat patients with MGC since 2004.This paper reported the comprehensive results of the 2 studies. Methods: All the patients who enrolled in our previous 2 phase Ⅱ trials and received EOF5 as first line treatment entered this study. Each patient received the treatment of epirubicin 50 mg/m2 iv d1, oxaliplatin 130 mg/m2 iv gtt d1 and 5-FU 375-425 mg/m2·d-1 civ 120 h, and repeated every 3 weeks. Efficacy was analyzed every 6 weeks. Results: A total number of 178 patients (all were metastatic patients but 2 advanced patients with unresectable lesions) were included into this study. One hundred and seventy patients were evaluable, and 7 patients (3.9%) achieved complete response (CR), 76 patients (42.7%) achieved partial response (PR), 46.6% patients achieved overall response rate (ORR, CR+PR), and the cases of stable disease (SD) and progressive disease (PD) were 69 (38.8%) and 18 (10.1%), respectively. The median progress free survival (PFS) and overall survival (OS) were 6.0 months (95%CI: 5.2-6.8) and 12.6 months (95%CI: 8.9-16.3), 1-year and 2-year survival rate were 50.9% and 28.0%, respectively. Grade 3, 4 toxicity including: leucopenia (23.0), neutropenia (38.8%), anemia (6.5%), thrombocytopenia (23.5%), nausea/vomiting (14.1%), and peripheral neuropathy toxicity (1.2%). Among 75 patients who received second line treatment, the median survival from second line treatment was 8.0 months (95%CI: 4.8-11.2). Conclusion: EOF5 regimen is a highly effective regimen with moderate and manageable toxicity, and it providesa suitable alternative for the first-line treatment of MGC.