Docetaxel, cisplatin and 5-fluorouracil in patients with locally advanced unresectable head and neck cancer: a phase I-II feasibility study
Docetaxel, cisplatin and 5-fluorouracil in patients with locally advanced unresectable head and neck cancer: a phase I-II feasibility study
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DOI：
10.1093/annonc/mdh145
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发表时间：
2004-04-01
影响因子：
50.5
通讯作者：
Vermorken, JB
中科院分区：
文献类型：
--
作者：
Schrijvers, D;Van Herpen, C;Vermorken, JB
目的：为了确定多西他赛，顺铂和5-氟尿嘧啶（5-FU）在化疗初治患者的头部和颈部鳞状细胞癌（SCCHN）的组合的安全性和活性。患者和方法：局部晚期不可切除的SCCHN患者接受多西他赛和顺铂治疗，均为1小时输注的第1天，然后连续输注5天的5-FU。计划每3周进行一个周期，最多4个周期，之后患者接受局部区域放射治疗。研究了两个剂量水平。水平I的剂量为多西他赛75 mg/m2、顺铂75 mg/m2和5-FU 750 mg/m2/天;水平II的顺铂剂量递增至100 mg/m2。化疗后，所有患者接受根治性放疗，根据标准在不同institutions.Results：25例患者治疗剂量水平I与86个周期（中位数4;范围1至4），和23在剂量水平II与84个周期（中位数4;范围2至4）。水平I和水平II的中位相对剂量强度分别为0.99（范围0.86-1.04）和0.94（范围0.79-1.02）。意向治疗人群的缓解率在I级为64% [95%置信区间（CI）42.5%-82%]，在11级为78.3%（95% CI 56.3%-92.5%）;均为部分缓解。在II级达到最大耐受剂量，肾毒性、恶心、口腔炎和血小板减少是主要的剂量限制性毒性。48例患者的中位生存期为18.5个月。结论：多西他赛、顺铂和5-FU联合环丙沙星预防性治疗SCCHN是可行的，疗效显著。推荐剂量水平I用于III期试验。
Purpose: To determine the safety profile and activity of the combination of docetaxel, cisplatin and 5-fluorouracil (5-FU) in chemotherapy-naive patients with squamous cell carcinoma of the head and neck (SCCHN).Patients and methods: Patients with locally advanced unresectable SCCHN were treated with docetaxel and cisplatin both as a 1-h infusion on day 1 followed by a continuous infusion of 5-FU for 5 days. Cycles were planned every 3 weeks up to four cycles, whereafter the patients were treated with locoregional radiotherapy. Two dose levels were studied. Doses in level I were 75 mg/m(2) of docetaxel, 75 mg/m(2) of cisplatin and 750 mg/m(2)/day of 5-FU; in level II the cisplatin dose was escalated to 100 mg/m(2). Following chemotherapy, all patients were to receive curative radiotherapy according to the standards in the different institutions.Results: Twenty-five patients were treated at dose level I with 86 cycles (median four; range one to four), and 23 at dose level II with 84 cycles (median four; range two to four). The median relative dose intensity was 0.99 (range 0.86-1.04) at level I and 0.94 (range 0.79-1.02) at level II. The response rate in the intention-to-treat population was 64% [95% confidence interval (CI) 42.5% to 82%] in level I and 78.3% (95% CI 56.3% to 92.5%) in level 11; all were partial responses. The maximum tolerated dose was reached at level II with renal toxicity, nausea, stomatitis and thrombocytopenia as principal dose-limiting toxicities. The median survival of the 48 patients was 18.5 months. The survival at 12, 18, 24 and 30 months was 69, 54,41 and 3 1%, respectively.Conclusions: The combination of docetaxel, cisplatin and 5-FU associated with prophylactic ciprofloxacin is feasible and active in patients with SCCHN. Dose level I is recommended for phase III testing.