一项 UFT（尿嘧啶和替加氟的固定组合）和亚叶酸联合给药（每日三次口服）治疗复发性转移性乳腺癌患者的 2 期研究。

A phase 2 study of a fixed combination of uracil and ftorafur (UFT) and leucovorin given orally in a 3-times-daily regimen to treat patients with recurrent metastatic breast cancer.

机构信息

Department of Breast Medical Oncology, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Box 424, Houston, TX 77030-4009, USA.

出版信息

Cancer. 2010 Mar 15;116(6):1440-5. doi: 10.1002/cncr.24900.

DOI:10.1002/cncr.24900

PMID:20091835

Abstract

BACKGROUND

A combination of uracil and ftorafur (UFT) was developed to combine the cytotoxic effects of 5-fluorouracil (5-FU) with convenient oral dosing. Leucovorin was combined with UFT to further potentiate the effect of 5-FU on tumor cells. Orally administered UFT and leucovorin provided higher peak plasma concentrations of 5-FU and prolonged therapeutic 5-FU concentrations compared with continuous infusion of 5-FU.

METHODS

Ninety-one patients with metastatic breast cancer who had been previously treated with anthracyclines and/or taxanes were treated with UFT and leucovorin, given orally, for the first 28 days of a 35-day cycle. The total daily dose of UFT was 300 mg/m(2), administered in 3 doses of 100 mg/m(2) each every 8 hours. The primary endpoint was time to disease progression (TTP). Secondary objectives included overall tumor response rate (overall response equals complete response plus partial response) and overall survival.

RESULTS

Of the 91 patients enrolled, 70 were evaluable for efficacy. Although no complete responses were observed, 7 patients had partial responses, for an overall response rate of 10% in the evaluable population. The median TTP for the evaluable population was 10 weeks, and the proportion of patients who were free of disease progression at 6 months was 23%. The median overall survival was 59.4 weeks for all patients enrolled. Common, drug-related > or = grade 3 adverse events (graded according to National Cancer Institute Common Toxicity Criteria, version 2) included diarrhea, vomiting, abdominal pain, and nausea.

CONCLUSIONS

The combination of UFT and leucovorin administered orally in a 3-times-daily regimen was found to have modest activity. Grade 3 toxicities were manageable with appropriate dose adjustments in patients with metastatic breast cancer previously treated with anthracyclines and/or taxanes.

摘要

背景

为了将 5-氟尿嘧啶（5-FU）的细胞毒性作用与方便的口服给药相结合，开发了尿嘧啶和替加氟（UFT）的组合。亚叶酸与 UFT 联合使用可进一步增强 5-FU 对肿瘤细胞的作用。与持续输注 5-FU 相比，口服给予 UFT 和亚叶酸可使 5-FU 的血浆峰浓度更高，并延长治疗性 5-FU 浓度。

方法

91 例先前接受过蒽环类药物和/或紫杉烷类药物治疗的转移性乳腺癌患者，在 35 天周期的前 28 天内接受 UFT 和亚叶酸，口服给药。UFT 的总日剂量为 300mg/m²，每 8 小时给予 3 次，每次 100mg/m²。主要终点是疾病进展时间（TTP）。次要目标包括总肿瘤反应率（总反应等于完全缓解加部分缓解）和总生存。

结果

在纳入的 91 例患者中，有 70 例可用于疗效评估。虽然未观察到完全缓解，但有 7 例患者有部分缓解，总反应率为可评估人群的 10%。可评估人群的中位 TTP 为 10 周，6 个月时无疾病进展的患者比例为 23%。所有入组患者的中位总生存时间为 59.4 周。常见的、与药物相关的≥3 级不良事件（根据国家癌症研究所常见毒性标准，版本 2 进行分级）包括腹泻、呕吐、腹痛和恶心。