Phase I trial of dose escalation of capecitabine combined with fixed docetaxel in previously treated patients with non-small cell lung cancer

卡培他滨联合固定剂量的多西紫杉醇化疗复治非小细胞肺癌的Ⅰ期临床试验(英文)

Objective： Capecitabine combined with docetaxel have demonstrated antitumor synergy for non-small cell lung cancer （NSCLC）. Due to absence of phase I trial in China, we conducted this study to define the maximum-tolerated dose （MTD） of capecitabine with fixed docetaxel for Chinese patients with previously treated NSCLC. Methods： Previously treated patients with NSCLC were entered into this study. Escalating doses of capecitabine with fixed docetaxel were administered in a modified Fibonacci sequence. The initial doses were capecitabine 625 mg/m2, bid, on days d5-d 18, and docetaxe130 mg/m2 on days 1 and 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 at which DLT appeared. Results： Eighteen patients received 67 cycles at capecitabine of level I （1250 mg/m2, divided into 625 mg/m2, bid） and level II （1500 mg/m2, 750 mg/m2, bid）. The 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 dose level I and 7 DLTs in dose level 2. Since 4 of 6 patients in level II experienced DLTs, we declared thus level I was MTD. Cunclusion： MTD of our phase I trial was capecitabine of 1250 mg/m2/d combined with docetaxel of 30 mg/m2/wk. This combination regimen was well tolerated for previously treated patients with NSCLC. The efficacy of this schedule is currently being further evaluated in a prospective phase II trial.