Fujitaka Kazunori, Hattori Noboru, Senoo Tadashi, Iwamoto Hiroshi, Ohshimo Shinichiro, Kanehara Masashi, Ishikawa Nobuhisa, Haruta Yoshinori, Murai Hiroshi, Kohno Nobuoki
Department of Molecular and Internal Medicine, Graduate School of Biomedical Science, Hiroshima University, Hiroshima 734-8551, Japan.
Oncol Lett. 2011 Jan;2(1):167-170. doi: 10.3892/ol.2010.218. Epub 2010 Nov 23.
S-1 is a novel oral fluorouracil prodrug that plays a role in non-small cell lung cancer (NSCLC). Docetaxel (DTX) is one of the standard agents for relapsed NSCLC. We performed a phase I study of DTX plus S-1 combination therapy as second-line treatment for NSCLC to determine the maximum tolerated dose (MTD) and recommended dose (RD). Patients with recurrent NSCLC, aged 20-74 years with an Eastern Cooperative Oncology Group performance status of 0-1 and measurable lesions, were enrolled. The treatment consisted of four dose levels. The patients received DTX (40-60 mg/m(2) intravenously on day 1) and S-1 (65-80 mg/m(2) orally, daily on days 1-14) for each 21-day cycle. Three to six patients were treated at each dose level with the two drugs, with MTD defined as the dose level at which dose-limiting toxicity (DLT) occurred in 33% of the patients. A total of 17 patients were enrolled. At dose level 4 (DTX, 60 mg/m(2); S-1, 80 mg/m(2)) 3 of 5 patients experienced DLT and this level was regarded as the MTD. Therefore, dose level 3 (DTX, 60 mg/m(2); S-1, 65 mg/m(2)) was selected as the RD for subsequent studies. The DLTs were neutropenia (grade 4) and mucositis (grade 3). The response rate was 5.9% (1 of 17 patients achieved a partial response) and 14 of 17 patients achieved stable disease. This combination regimen showed a tolerable and manageable profile in recurrent NSCLC and therefore warrants further evaluation.
S-1是一种新型口服氟尿嘧啶前体药物，在非小细胞肺癌（NSCLC）中发挥作用。多西他赛（DTX）是复发性NSCLC的标准治疗药物之一。我们进行了一项关于DTX加S-1联合治疗作为NSCLC二线治疗的I期研究，以确定最大耐受剂量（MTD）和推荐剂量（RD）。纳入年龄在20 - 74岁、东部肿瘤协作组体能状态为0 - 1且有可测量病灶的复发性NSCLC患者。治疗分为四个剂量水平。患者每21天为一个周期，接受DTX（第1天静脉注射40 - 60 mg/m²）和S-1（第1 - 14天口服65 - 80 mg/m²，每日一次）。每个剂量水平用这两种药物治疗3至6名患者，MTD定义为33%的患者出现剂量限制性毒性（DLT）的剂量水平。共纳入17例患者。在剂量水平4（DTX，60 mg/m²；S-1，80 mg/m²）时，5例患者中有3例出现DLT，该水平被视为MTD。因此，剂量水平3（DTX，60 mg/m²；S-1，65 mg/m²）被选为后续研究的RD。DLT为中性粒细胞减少（4级）和黏膜炎（3级）。缓解率为5.9%（17例患者中有1例达到部分缓解），17例患者中有14例病情稳定。这种联合方案在复发性NSCLC中显示出可耐受和可管理的特征，因此值得进一步评估。
