Oxaliplatin with high-dose leucovorin and 5-fluorouracil 48 hour continuous infusion in pretreated metastatic colorectal cancer
Oxaliplatin with high-dose leucovorin and 5-fluorouracil 48 hour continuous infusion in pretreated metastatic colorectal cancer
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DOI：
10.1016/s0959-8049(96)00370-x
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发表时间：
1997-02-01
影响因子：
8.4
通讯作者：
Krulik, M
中科院分区：
文献类型：
--
作者：
deGramont, A;Vignoud, J;Krulik, M
奥沙利铂已显示出对结直肠癌细胞系的体内细胞毒活性。初步研究表明其对氟尿嘧啶（5 - FU）有增效作用。为评估这一问题，我们对先前接受过治疗且对亚叶酸钙和5 - FU耐药的晚期结直肠癌（CRC）患者进行了一项II期研究。该方案（FOLFOX2）包括：在第1天奥沙利铂100 mg/m²，持续2小时输注；亚叶酸钙500 mg/m²，持续2小时输注，随后氟尿嘧啶1.5 - 2 g/m²持续24小时输注，每2周连续2天。最初两个周期氟尿嘧啶剂量为1.5 g/m²，如果无大于2级的毒性反应，则增加到2 g/m²。共治疗了46例患者，所有患者在因转移性疾病接受亚叶酸钙和5 - FU治疗时均出现疾病进展，或者在辅助治疗结束后不到6个月复发。观察到1例完全缓解（CR）和20例部分缓解（PR），总缓解率为46%。22例患者在接受与FOLFOX2方案中相同的亚叶酸钙和5 - FU给药方案时已有疾病进展记录，其中10例患者达到部分缓解（45%）。从开始FOLFOX2治疗起，中位无进展生存期为7个月，中位生存期为17个月。每位患者世界卫生组织（WHO）3级及以上毒性反应如下：周围神经病变9%、恶心4%、腹泻9%、黏膜炎13%、中性粒细胞减少症39%、血小板减少症11%、脱发9%、过敏2%。总体而言，21例患者（46%）出现3 - 4级毒性反应。这种亚叶酸钙、5 - FU和奥沙利铂的联合用药在先前接受过治疗且对亚叶酸钙和5 - FU耐药的结直肠癌患者中取得了较高的缓解率。主要的限制性毒性是中性粒细胞减少症和周围神经病变。（C）1997年爱思唯尔科学有限公司
Oxaliplatin has shown in vivo cytotoxic activity against colorectal cell Lines. Preliminary studies suggest potentiation of fluorouracil (5-FU). To assess this issue, we performed a phase II study in pretreated patients with advanced colorectal cancer (CRC) resistant to leucovorin and 5-FU. The regimen (FOLFOX2) consisted of oxaliplatin 100 mg/m(2) as a 2-h infusion on day 1; leucovorin 500 mg/m(2) as a 2-h infusion, followed by 5-FU 24-h infusion 1.5-2 g/m(2) for two consecutive days every 2 weeks. The initial 5-FU dose was 1.5 g/m(2) for two cycles and increased to 2 g/m(2) in case of no toxicity>grade 2. 46 patients were treated, all with disease progression on leucovorin and 5-FU therapy for metastatic disease, or relapse less than 6 months after the end of adjuvant therapy. One complete response (CR) and 20 partial responses (PRs) were observed for an overall response rate of 46%. 22 patients had prior documented progression while receiving the same schedule of leucovorin and 5-FU as the one used in the FOLFOX2 regimen, and among them, 10 had PRs (45%). From the start of FOLFOX2, median progression-free survival was 7 months and median survival 17 months. WHO toxicity greater than or equal to grade 3 per patient was: peripheral neuropathy 9%, nausea 4%, diarrhoea 9%, mucositis 13%, neutropenia 39%, thrombocytopenia 11%, alopecia 9%, and allergy 2%. Overall, 21 patients (46%) experienced grade 3-4 toxicity. This combination of leucovorin, 5-FU and oxaliplatin achieves a high response rate in pretreated patients with CRC resistant to leucovorin and 5-FU. Limiting toxicities are neutropenia and peripheral neuropathy. (C) 1997 Elsevier Science Ltd.