奥沙利铂单药或与氟尿嘧啶-甲酰四氢叶酸联合应用治疗晚期大肠癌Ⅱ期临床试用报告

A multicenter randomized phase II trial of oxaliplatin in patients with advanced colorectal cancer

目的：观察奥沙利铂治疗晚期大肠癌的临床疗效和安全性。方法：根据ＧＣＰ指导原则开展多中心Ⅱ期随机临床研究：Ａ组奥沙利铂单药１３０ｍｇ／ｍ２静脉滴注２ｈ，每３周一次；Ｂ组奥沙利铂１３０ｍｇ／ｍ２静脉滴注２ｈＤ１，加甲酰四氢叶酸钙（ＣＦ）２００ｍｇ／ｍ２＋５氟尿嘧啶３００ｍｇ／ｍ２静脉滴注４ｈＤ１到Ｄ５，每３周一次。治疗３周期后评定疗效，有效病例在４周后确认疗效。结果：共收入１１４例，在可统计近期疗效的１００例中，ＣＲ１例，ＰＲ２６例，ＳＤ３２例，ＰＤ４１例，总有效率２７０％。Ａ组３６例单药治疗有效率为１３９％；Ｂ组６４例有效率为３４４％。不良反应主要为恶心、呕吐、贫血和感觉神经毒性。对白细胞和血小板影响较小。结论：经考核奥沙利铂对大肠癌疗效和不良反应与欧洲的结果相近，和氟尿嘧啶合用疗效突出；多数病人耐受良好，是一治疗大肠癌有希望的新药。进一步考核，奥沙利铂和氟尿嘧啶联合有望成为治疗晚期大肠癌的首选方法。

Objectives: Oxaliplatin(eloxatin, LOHP)has shown activity in advanced colorectal cancer (ACRC) both as a monotherapy and in combination with 5FU/FA in both chemonaive and pretreated paitents. The aim of this project was to evaluate the efficacy and adverse effects of LOHP in Chinese colorectal patinets. Methods: A randomized phase study of this drug versus combination with 5FU/FA in ACRC patients was conducted in China for the first time in 15 centers. Arm A:LOHP 130 mg/m2, iv infusion for 2 h, repeat every 3 weeks; Arm B:LOHP 130 mg/m22 hD1 combined with folinic acid 200 mg/m22 h followed by 5fluorouracil 300 mg/m24 h D1 to D5, repeat every 3 weeks. Tumor assessment dosdone every 3 cycles and responders were confirmed four weeks later. Results: 114 ACRC patients entered the study, 100 cases evaluable for efficacy, one patient reached complete response, 26 partial response, 32 stable disease, and 41 with progression after treatment, the response rate for the whole group was 270%. There were 5 PR, 12 SD, and 19 PD in arm A, the response rate being 139%(5/36); while there were 1 CR, 21 PR, 20 SD and 22 PD in arm B, the response rate being 344%(22/64). The main adverse effects were nausea and vomiting, anemia and neurosensory toxicity, while bone marrow suppression was mild. Conclusion: The response rate in both arms was encouraging and comparable with the Europan data on LOHP activity. Combination treatment and monotherapy were equally well tolerated. Furthermore these results support the combination schedule as standard treatment for routine management of ACRC in China.