卡培他滨二线治疗非小细胞肺癌的剂量递增研究

目的 探讨卡培他滨(capecitabine,CAPE)联合多西紫杉醇(docetaxel,TXT)二线治疗非小细胞肺癌(NSCLC)时卡培他滨的最大耐受剂量(maximum-tolerated dose,MTD).方法 应用改良的Fibonacci法给予复治的NSCLC患者递增剂量的CAPE联合固定剂量TXT化疗,剂量Ⅰ(625 mg/m2,每天2次)和剂量Ⅱ(7 50 mg/m2,每天2次),两组1 8例患者共接受了67周期化疗.起始剂量为CAPE625 mg/m2,每天2次,d5～d18,TXT 30 mg/m2,d1,d8,每21天重复.如果没有剂量限制性毒性(dose limiting toxicity,DLT)出现,则升至下一剂量组,直至出现DLT.MTD定义为DLT出现的剂量水平的低一剂量.结果 主要的不良反应为粒细胞减少症、手足综合征、乏力和恶心.全组共5例发生8个DLT,剂量Ⅰ组1个(1例患者),剂量Ⅱ组7个(4例患者).由于在剂量Ⅱ组6例患者中4例出现了DLT,根据定义笔者确定剂量T为MTD.结论 此剂量递增试验的MTD是:卡培他滨1 250 mg/(m2·d)(625 mg/m2,每天2次)联合多西紫杉醇30mg/m2,d1,d8,每21天重复.复治NSCLC患者对此联合方案耐受性良好.

Dose Escalation of Capecitabine as Second-line Chemotherapy for Patients with Non-small Cell Lung Cancer

ObjectiveTo define the maximum-tolerated dose (MTD) of capecitabine with fixed docetaxel for Chinese patients with previously treated NSCLC.MethodsEscalating doses of capecitabine with fixed docetaxel were administered in a modified Fibonacci sequence.Eighteen patients received 67 cycles at capecitabine of level I (1 250 mg/m²,divided into 625 mg/m²,bid) and level Ⅱ (1 500 mg/m² 750 mg/m²,bid).The initial doses were capecitabine 625 mg/m²,bid,on day d5-d18,and docetaxel 30 mg/m² on days 1,8,respectively.The regimen was repeated every 21 days.If no dose-limiting toxicity (DLT) was observed,the next dose level was applied.The procedures were repeated until DLT appeared.The MTD was declared to be one dose level below the level without DLT.ResultsThe most common toxicities were neutropenia,hand and feet syndrome,fatigue and nausea.Eight DLTs occurred in 5 patients in the whole group,including 1 DLT in 1 patient at dose level I and 7 DLTs in 4 patients at dose level 2.Since 4 of 6 patients in level II experienced DLTs,we declared that level I was MTD.ConclusionMTD of our escalation trial was capecitabine of 1 250 mg/(m²·d) (625 mg/m2,bid) combined with docetaxel of 30mg/m²,d1,d8,repeated every 21 days.This combination regimen was well tolerated for previously treated patients with NSCLC.