A phase II study of modulated-capecitabine and docetaxel in chemonaive patients with advanced non-small cell lung cancer (NSCLC).
A phase II study of modulated-capecitabine and docetaxel in chemonaive patients with advanced non-small cell lung cancer (NSCLC).
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调节卡培他滨和多西紫杉醇治疗晚期非小细胞肺癌 (NSCLC) 化疗患者的 II 期研究。
DOI：
10.1016/j.lungcan.2012.09.013
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发表时间：
2013
期刊：
影响因子：
--
通讯作者：
Villalona-Calero,MiguelA
中科院分区：
文献类型：
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作者：
Bertino,ErinM;Bekaii-Saab,Tanios;Fernandez,Soledad;Diasio,RobertB;Karim,NaglaA;Otterson,GregoryA;Villalona-Calero,MiguelA
简介 这项在既往未经治疗的非小细胞肺癌 (NSCLC) 患者中进行多西紫杉醇和卡培他滨的 II 期单臂试验旨在根据在既往治疗的 NSCLC 患者中进行的 II 期测试的有希望的疗效数据来评估该方案的缓解率。该试验还评估了外周血二氢嘧啶脱氢酶（DPD）表达与疗效/毒性之间的相关性。方法纳入未接受化疗的晚期NSCLC（转移性，包括恶性胸腔积液）患者。进行基线 DPD 筛查；基线 DPD 水平<0.07nmol/min/mg 蛋白质的患者被认为不符合该研究的资格。治疗包括为期 28 天的周期，在第 1、8、15 天使用多西紫杉醇 36mg/m2，在第 5-18 天分次使用卡培他滨 1250mg/m2/天。总体缓解率 (RR) 是主要终点，目标 RR 为 50%。相关研究包括评估外周血中的 DPD 活性水平以及与临床反应的相关性。结果 28 名患者接受了 86 个周期的治疗（中位 3 个周期），并且可以评估反应。 RR 为 18%（5 名患者）； RR 未达到预先指定的疗效终点，试验被停止。 14 名患者疾病稳定 (SD – 50%)，4 名患者的 SD > 12 周。中位进展时间为 3.3 个月（95% CI 1.5-4.6 个月）。中位总生存期为 10.5 个月（95% CI：3.2-15 个月）。主要毒性包括疲劳、口腔炎和白细胞减少。 DPD 水平范围为 0.06 至 0.26nmol/min/mg。大多数应答者 (4/5) 的 DPD 水平≤0.1nmol/min/mg。大多数响应者 (4/5) 经历了 3 级毒性，包括白细胞减少、脱水、疲劳和腹泻。具有较高 DPD 水平 (>0.2nmol/min/mg) 的患者 (0/4) 均未出现缓解。 结论 该方案的缓解率未表现出足够的活性，并且未表明在此情况下对该方案进行进一步研究。有趣的是，结果表明低 DPD 表达可能与卡培他滨的反应有关，但也与毒性增加有关。
INTRODUCTIONThis phase II single-arm trial of docetaxel and capecitabine in previously untreated non-small cell lung cancer (NSCLC) patients was designed to evaluate response rate of this regimen based on promising efficacy data from phase II testing in pre-treated NSCLC patients. The trial also evaluated the correlation between peripheral blood dihydropyrimidine dehydrogenase (DPD) expression and efficacy/toxicity.METHODSPatients with advanced NSCLC (metastatic, including malignant pleural effusion) without prior chemotherapy were enrolled. Baseline DPD screening was performed; patients with baseline DPD level <0.07nmol/min/mg protein were considered ineligible for the study. Treatment included a 28-day cycle of docetaxel 36mg/m2on days 1, 8, 15 and capecitabine 1250mg/m2/day in divided doses on days 5–18. Overall response rate (RR) was the primary endpoint with a target RR of 50%. Correlative studies included evaluation of DPD activity levels in peripheral blood and correlation with clinical responses.RESULTSTwenty-eight patients received 86 cycles of treatment (median 3 cycles) and were evaluable for response. The RR was 18% (5 patients); RR did not meet the pre-specified efficacy endpoint and the trial was stopped. 14 patients had stable disease (SD – 50%) and 4 patients had SD>12 weeks. Median time to progression was 3.3 months (95% CI 1.5–4.6 months). Median overall survival was 10.5 months (95% CI: 3.2–15 months). Main toxicities included fatigue, stomatitis and leukopenia. DPD levels ranged from 0.06 to 0.26nmol/min/mg. The majority of responders (4/5) had DPD levels ≤0.1nmol/min/mg. Most of the responders (4/5) experienced grade 3 toxicities including leukopenia, dehydration, fatigue, and diarrhea. None of the patients (0/4) with higher DPD levels (>0.2nmol/min/mg) had a response.CONCLUSIONThe response rate for the regimen did not demonstrate sufficient activity and further study of this regimen in this setting is not indicated. Interestingly, the results suggest that low DPD expression may be associated with response to capecitabine but also with increased toxicity.