卡培他滨应用于鼻咽癌同期放化疗的Ⅰ期临床试验

Phase Ⅰ Clinical Trial Evaluation of Capecitabine in Concurrent Combination of Radiotherapy in Nasopharyngeal Carcinoma

背景与目的:卡培他滨(capecitabine)是一种口服的氟尿嘧啶类药物。在肿瘤组织中,由特异高表达的胸腺嘧啶磷酸化酶(thymidinephosphorylase,TP酶)转变为5-氟尿嘧啶(5-fluorouracil,5-FU),因此在肿瘤细胞内5-FU浓度较高。本试验探讨卡培他滨在鼻咽癌同期放化疗的最大耐受剂量(maximumtolerateddose,MTD)。方法:对36例病理诊断为鼻咽癌的放疗患者同时给予不同剂量单药卡培他滨化疗,观察不良反应并随访治疗效果。卡培他滨采用间断服用方法,放疗后开始口服,每天2次,服药14天,然后休息7天,再开始第二疗程化疗,一共2疗程。中位剂量为1600mg·(m2·d)-1,剂量为700～2500mg·(m2·d)-1。放疗剂量66～74Gy(6～7.4周)。结果:2例Ⅲ级剂量限制性毒性(dose-limitingtoxicity,DLT)发生在2300mg·(m2·d)-1剂量组,1例为Ⅲ级腹泻,1例为Ⅲ级手足综合症(hand-footsyndrome,HFS)。结论:鼻咽癌患者对卡培他滨单药化疗联合同期放疗耐受良好,最大耐受剂量为2300mg·(m2·d)-1。我们推荐卡培他滨Ⅱ期临床试验的剂量为1700mg·(m2·d)-1(间断服用方法)。

BACKGROUND & OBJECTIVE:Capecitabine is an oral fluoropyri- mi dine, which is converted to fluorouracil (5- FU) by exploiting the comparativel y higher activity of thymidine phosphorylase (TP) in tumor tissue. This study wa s designed to measure the maximum tolerated dose (MTD) of capecitabine in the pa tients with nasopharyngeal carcinoma. METHODS: Medical records of 36 patients wi th nasopharyngeal carcinoma treated with radiation and capecitabine were reviewe d. The median dose of capecitabine was 1 600 mg· (m2· d)- 1 [700- 2 500 mg· (m2· d)- 1] orally for 2 weeks followed 1 week of rest and then another cycle . All the patients received a total dose ranging from 66 Gy to 74 Gy over 6- 7. 4 weeks. RESULTS: In the 2 300 mg· (m2· d)- 1 group, Grade Ⅲ toxicities obs erved were hang- foot syndrome (1 patient) and diarrhea (1 patient). CONCLUSION : Concurrent administration of capecitabine and radiation were tolerable in the patients with nasopharyngeal carcinoma. The maximum tolerated dose is 2 300 mg· (m2· d)- 1, The recommended phase Ⅱ dose is 1 700 mg· (m2· d)- 1 dai ly administered by this intermittent schedule.