常规放疗加每周紫杉醇治疗局部晚期鼻咽癌的临床Ⅰ期试验  

Radiation therapy and concomitant weekly paclitaxel for locally advanced nasopharyngeal carcinoma: outcomes of a phase I trial

作　　者：陈明[1] 吴少雄[1] 陈媛媛[1] 林焕新[1] 冼超贵[1] 邓小武[1] 卢泰祥[1] 崔念基[1] 

机构地区：[1]中山大学附属肿瘤医院放疗科,广东广州510060

出　　处：《中国癌症杂志》2002年第3期245-248,共4页China Oncology

摘　　要：目的 :评价常规放疗的同时每周 1次紫杉醇持续 3小时滴注治疗局部晚期鼻咽癌的剂量限制性毒性(dose-limitingtoxicity ,DLT ) ,确定此治疗模式下紫杉醇的最大耐受剂量 (maximaltolerantdose,MTD)。方法 :局部晚期鼻咽癌患者随机进入前瞻性临床I期试验。急性毒性按常见毒性评价标准 (CommonToxicityCriteria:Ver sion 2 .0 ,CTC 2 .0 )分级 ,紫杉醇MTD定义为≥ 2 / 6患者出现DLT剂量水平的下一级剂量。紫杉醇每周 1次 ,持续静滴 3小时 ,开始剂量 2 0mg/m2 ,每个剂量水平治疗 3例 ,如无DLT发生则逐次递增 10mg/m2 。放疗每周 5次 ,每次 2Gy ,总剂量 6 8～ 70Gy。结果 :2 0 0 0年 12月～ 2 0 0 1年 6月 ,16例患者按计划完成了治疗。在 2 0mg/m2剂量水平未发生DLT ,30mg/m2 水平 1/ 3患者发生Ⅲ级口咽部粘膜炎并持续 5周 ,再以此剂量治疗的 3例未发生DLT。 4 0mg/m2 水平的 3例中 1例发生Ⅲ级粘膜炎并持续 4周 ,1例发生Ⅲ级皮肤损伤并持续 4周。为增加试验的可靠性 ,再以 30mg/m2 治疗了 4例患者 ,未有DLT发生。按照计划试验到此停止。中位随访 12个月后 ,1例放疗后 6个月死于多发性骨转移 ,1例右上颈淋巴结足量照射后残留 ,观察至 3个月时 ,淋巴结开始增大 ,予以手术摘除。其余 14例均无瘤生存。结论Purpose:A phase I trial of radiotherapy concomitantly with weekly paclitaxel was carried out to define the maximal tolerant dose (MTD) by describing the dose limiting toxicity (DLT) of paclitaxel given as a 3 hour Ⅳ infusion in patients with locally advanced nasopharyngeal carcinoma (NPC). Methods:Patients with locally advanced NPC were enrolled into a prospective, dose escalating phase I study. Toxicity was graded according to CTC 2.0. MTD was defined when two out of six patients developed DLT. The starting dose of paclitaxel was 20 mg/m 2 once weekly IV over 3 hours, with a subsequent dose escalation of 10 mg/m 2 in cohorts of three new patients. Radiation therapy was administered with conventional technique over 7 weeks in 2.0 Gy/daily fractions for 5 days/week up to total doses of 68～70 Gy.Results:From December 2000 to June 2001, sixteen patients completed chemoradiotherapy, and all of them were eligible for toxicity evaluation. On the first dose level (20 mg/m 2 ) no patient experienced DLT. On the next dose level with 30 mg/m 2 , one patient experienced DLT with grade Ⅲ mucositis for 5 weeks, and among the additional 3 patients no one developed DLT. On the third dose level with 40 mg/m 2 , one patient developed grade Ⅲ mucositis for 4 weeks and another suffered from grade Ⅲ dermatitis for 4 weeks. In order to make the trial more credible, another 4 patients were added to 30 mg/m 2 level, and no DLT occurred. Thus, the accumulation of patients stopped. After a median follow-up 12 months, one patient died of multiple bone metastases. One patient needed an operation to eradicate the residual right upper cervical lymph node 3 months after radical irradiation. Fourteen patients survived with disease free condition.Conclusions:When paclitaxel is given weekly as a 3 hour infusion concomitant to conventional radiotherapy for locally advanced NPC, MTD is 30 mg/m 2 with mucositis and dermatitis as DLT, and other toxicities are mild.

关 键 词：治疗 鼻咽癌 紫杉醇 放疗 耐受剂量 MTD 

分 类 号：R739.63[医药卫生—肿瘤]