局部进展期鼻咽癌同期放化疗卡培他滨联合顺铂剂量递增的Ⅰ期临床研究

Satge I clinical study of dose escalation of capecitabine during intensity modulated radiotherapy concurrent chemotherapy for local regional advanced nasopharyngeal carcinoma

目的 探讨鼻咽癌同期放化疗对卡培他滨递增剂量以降低患者不良反应的方法.方法 2006年8月至2007年10月,24例Ⅲ-Ⅳ期的鼻咽癌患者在北京大学临床肿瘤学院入组接受了调强放疗以及卡培他滨联合顺铂方案的同期化疗.调强放疗采用瓦里安的Eclipse调强治疗计划系统,同步推量.同期化疗3个周期,每21天为1周期.顺铂为固定剂量20 mg·m^-2·d^-1（第1至5天）,卡培他滨剂量从625至1250 mg·m^-2·d^-1分为4个剂量水平,MRI和CT影像用于肿瘤消退评价.CTC 3.0评分标准用于评价近期治疗相关的不良反应.结果 近期治疗相关不良反应主要表现为放射性黏膜炎、皮肤反应和骨髓抑制,并随着化疗药物剂量的增加而加重.观察625和825 mg/m^2组中未出现≥3度非黏膜性反应和持续5 d以上的≥3度黏膜反应,1000组和1250 mg/m^2组中上述反应分别出现6例和3例.剂量限制性毒性反应主要是放射性黏膜炎和骨髓抑制,近期不良反应与卡Ⅳ培他滨剂量递增呈明显相关性（P〈0.05）.中位随访时间为28.5个月,局部复发2例,远地转移2例.2年总生存率100%,无瘤生存率87.5%,局部控制率91.7%.放疗结束时和放疗后3个月影像学评价完全缓解率（CR）分别是29.2%和83.3%.结论 局限进展期鼻咽癌调强放疗联合顺铂＋卡培他滨化疗方案安全、方便.同期调强放化疗的近期不良反应程度与联合化疗方案中卡培他滨剂量呈明显相关.

Objective To decrease radiation induced toxicities especially mucostis in patients with locally advanced nasopharyngeal carcinoma（ NPC ） who underwent concurrent radiochemotherapy, the maximum tolerated dose and dose limited toxicities of capecitabine combination with cisplatin were observed. Methods From Aug 2006 to Oct 2007, 24 patients with intensity modulated radiotherapy（IMRT） and concurrent chemotherapy with capecitabine and cisplatin for nasopharyngeal carcinoma（stages Ⅲ-Ⅳ） were enrolled in this study. There were four dose-level groups of Capecitabine[625-1250 mg/（m^2 ·d） , d1-14]and fixed cisplatin dose[20 mg/（m ·d） ,d1-5） ]MRI and CT scan were used for evaluation of tumor shrinkage. Treatment related toxicities were evaluated according to the common toxicity criteria（ NCI-CTC Version 3.0）. Results The acute side-effects include Grade 3 or Grade 4 mucosal toxicity（lasting for at least 5 d） and Grade 3 or Grade 4 non-mucosal toxicity were evaluated. Group 625 mg/m^2 and Group 825 mg/m^2 had none, Group 1000 mg/m^2 had 6 patients and Group 1250 mg/m^2 had 3 patients for mucosal toxicity, which were the main dose-limited toxicity and relevant to the dose of capecitabine apparently（ P 〈 0. 05 ）. There was also a trend of increase by the dose level of capecitabine for other toxicities. The median follow-up time for all patients was 28. 5 months. The locoregional recurrence occurred in 2 patients and distant metastasis in 2 patients. Two-year overall survival rate and locoregional control rate were 100% and 91.7%, respectively.Complete response and partialresponse were found on MRI or CT scan in patients of 29. 2% at the end of treatment and 83. 3% after three months, respectively. Conclusions The combination regimen of capecitabine and cisplatin is safe and effective according to the preliminary result. Toxicities related to radiochemotherapy for NPC were significantly associated with the dose level of chemotherapy.