早期鼻咽癌希罗达增敏放疗的临床Ⅰ期研究

Phase I study of capecitabine with concurrent radiotherapy in early-stage nasopharyngeal carcinoma

目的 探讨希罗达对鼻咽癌增敏放疗的剂量限制毒性 (DLT)和最大耐受剂量 (MTD) ,同时观察疗效。方法 自 2 0 0 2年 8月至 2 0 0 3年 6月 ,临床分期为T2 N1M0 的Ⅱ期鼻咽癌患者 30例 ,中位年龄 4 3岁 (32～ 6 3岁 ) ,全身功能状态评分≤ 2。放射治疗为鼻咽原发病灶 6 8～ 72Gy·34～ 36次 -1·7周 -1,颈部淋巴结阳性区 6 4～ 70Gy·32～ 35次 -1·6 .5～ 7周 -1。希罗达分为 5 0 0 ,75 0 ,10 0 0 ,12 5 0mg/m2 等 4个剂量组 ,于放疗第 1天开始 ,2次 /d ,共 14d ,每 3周为 1个疗程 ,共两个疗程。每个剂量组至少 6例患者 ,6例全部完成两个疗程化疗并进行毒性反应评价后 ,才进行剂量升级。结果 全组有 2 8例可评价疗效和毒性反应。希罗达治疗结束时 ,CR 12例 (42 .9% ) ,PR 13例 (46 .4 % ) ,SD 3例(10 .7% ) ,总有效率 (CR +PR)为 89.3%。单纯颈部淋巴结CR率为 5 0 .0 % (14 / 2 8) ,单纯鼻咽肿瘤CR率为 4 6 .4 % (13/ 2 8)。放射治疗结束时CR率为 96 .4 % (2 7/ 2 8)。希罗达 5 0 0mg/m2 和 75 0mg/m2剂量组未出现任何严重DLT ;在 10 0 0mg/m2 剂量组 ,有 3例 (3/ 9)出现Ⅲ级口腔黏膜DLT ;在 12 5 0mg/m2 剂量组 ,有 4例出现DLT ,其中Ⅲ度口腔黏膜反应 4例 (4/ 6 ) 。

Objective To evaluate the dose-limiting toxicity (DLT),efficacy and maximum tolerated dose (MTD) of capecitabine with concurrent radiotherapy in patients with node-positive stage Ⅱ nasopharyngeal cancer. Methods From August 2002 to June 2003,30 patients with node-positive stage Ⅱ T 2N 1M 0 nasopharyngeal cancer were retrospectively reviewed. Median age 43 years (range 32～63 years),ECOG performance status ≤2. Radiotherapy of 68～72 Gy/34～36 fractions was delivered to the nasopharynx and 64～70 Gy/32～35 fractions to the node-positive area. Capecitabine was administered orally on day 1 of radiotherapy by an intermittent schedule (14 days treatment;7-day rest) at 3 weekly intervals for two cycles. Patients were alloted into one of four escalating dose cohorts (500,750,1000 and 1250 mg/m 2,bid). Dose escalation was done after six patients had completed 2 cycles of chemotherapy at the previous dose level with DLT assessed. Results Twenty-eight patients were evaluable for toxicity and efficacy: CR 12 (42.9%),PR 13(46.4%),SD 3 (10.7%),the overall response rate (CR+PR) was 89.3%. The CR response rate of the node-positive area and of the nasopharynx were 50.0%(14/28) and 46.4%(13/28). No DLT was observed at the dosage group of 500 mg/m 2 and 750 mg/m 2. Three of 9 patients experienced DLT at 1000 mg/m 2 with grade Ⅲ stomatitis;4 of 6 at 1250 mg/m 2 with grade Ⅲ stomatitis (4/6),grade Ⅲ diarrhea with grade Ⅳ febrile neutropenia (1/6) and grade Ⅲ thrombocytopenia (1/6). The toxicity of grade Ⅰ and Ⅱ was hand-foot syndrome (4/28),fatigue(14/28),nausea and vomiting (19/28),diarrhea (5/27),and weight loss(21/28). Conclusion A dose of 750 mg/m 2 of capecitabine might be recommended for combination with radiotherapy. This regimen is tolerable and valid for nasopharyngeal carcinoma. A randomised phase Ⅲ comparison with 5-Fu is justified.