Phase I/II study of preoperative oxaliplatin, fluorouracil, and external-beam radiation therapy in patients with locally advanced rectal cancer: Cancer and leukemia group B 89901
Phase I/II study of preoperative oxaliplatin, fluorouracil, and external-beam radiation therapy in patients with locally advanced rectal cancer: Cancer and leukemia group B 89901
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DOI：
10.1200/jco.2006.05.6754
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发表时间：
2006-06-01
影响因子：
45.3
通讯作者：
Mayer, RJ
中科院分区：
文献类型：
--
作者：
Ryan, DP;Niedzwiecki, D;Mayer, RJ
目的：奥沙利铂联合氟尿嘧啶治疗晚期结直肠癌可提高生存率。本I/II期研究评价了局部晚期直肠腺癌患者术前连续输注氟尿嘧啶（FU）和外照射放射治疗（RT）的基础上每周加用奥沙利铂的情况。患者和方法临床T3/T4直肠腺癌且无转移证据的患者接受每周奥沙利铂治疗，连续输注FU 200 mg/m2静脉内，共计划每周6次奥沙利铂给药。RT剂量为1.8戈伊/次，总剂量为50.4戈伊。在I期部分，奥沙利铂从30至60 mg/m2（2）.ResultsForty-four患者进入研究，18对I期部分和26对11期部分。奥沙利铂的最大耐受剂量（MTD）确定为60 mg/m2。在MTD时，12例患者发生3级或4级腹泻，2例患者发生3级中性粒细胞减少，1例患者发生3级血小板减少。五十六%以MTD入组的患者完成了所有6周奥沙利铂治疗。八（25%）的32例患者在第二阶段的剂量经历了病理完全respons.ConclusionIn这个多中心研究，奥沙利铂静脉持续输注FU和RT局部晚期直肠癌患者与高病理完全缓解率，但更多的毒性比FU单独使用。每周一次奥沙利铂、持续输注FU和放射治疗的方案目前正在由国家外科辅助乳腺和肠道项目进行评估。
PurposeThe addition of oxaliplatin to fluorouracil in patients with advanced colorectal cancer improves survival. This phase I/II study evaluated the addition of weekly oxaliplatin to preoperative continuous infusion fluorouracil (FU) and external-beam radiation therapy (RT) in patients with locally advanced rectal adenocarcinoma.Patients and MethodsPatients with clinical T3/T4 rectal adenocarcinoma and no evidence of metastases were treated with weekly oxaliplatin, continuous infusion FU 200 mg/m(2) intravenously, and RT. A total of 6 weekly doses of oxaliplatin were planned. RT dose was 1.8 Gy/fraction to a total dose of 50.4 Gy. In the phase I portion, oxaliplatin was escalated from 30 to 60 mg/m(2).ResultsForty-four patients were entered onto the study, 18 on the phase I portion and 26 on the phase 11 portion. The maximum-tolerated dose (MTD) for oxaliplatin was determined to be 60 mg/m(2). At the MTD, 12 patients experienced grade 3 or 4 diarrhea, two patients experienced grade 3 neutropenia, and one patient experienced grade 3 thrombocytopenia. Fifty-six percent of patients entered at the MTD completed all 6 weeks of oxaliplatin. Eight (25%) of 32 patients enrolled at the phase II dose experienced a pathologic complete response.ConclusionIn this multicenter study, the addition of oxaliplatin to intravenous continuous infusion FU and RT for patients with locally advanced rectal cancer was associated with a high pathologic complete response rate but more toxicity than when FU is used alone. A regimen of weekly oxaliplatin, continuous infusion FU, and radiation therapy is now being evaluated by the National Surgical Adjuvant Breast and Bowel Project.