A dose-escalation study of docetaxel, oxaliplatin, and S-1 (DOS) as a first-line therapy for patients with unresectable metastatic gastric cancer
A dose-escalation study of docetaxel, oxaliplatin, and S-1 (DOS) as a first-line therapy for patients with unresectable metastatic gastric cancer
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DOI：
10.1007/s00280-018-3719-0
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发表时间：
2019-01-01
影响因子：
3
通讯作者：
Takayama, Tetsuji
中科院分区：
文献类型：
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作者：
Sato, Yasushi;Sagawa, Tamotsu;Takayama, Tetsuji
本研究的目的是确定多西紫杉醇/奥沙利铂/S-1(DOS)方案治疗不能切除的胃癌患者的推荐剂量(RD)，并初步评价其疗效。多西紫杉醇和奥沙利铂于第8天静脉注射，S-1于第1~14天口服，2次/d。每个周期每3周重复一次。在第一个治疗周期中评估剂量限制毒性(DLTS)。本研究采用3种剂量递增方案：1级(50/100/80 mg/m(2))、2级(50/130/80 mg/m(2))和3级(60/130/80 mg/m(2))。结果根据3+3剂量递增时间表，确定该方案的RD和最大耐受量分别为1级和2级。DLT为3级腹泻和发热中性粒细胞减少症。可测量皮损患者的总有效率为78%(7/9)，包括2个完全反应和5个部分反应。5例患者接受了中转手术。中位随访时间为19个月，中位生存期为19.6个月，无进展生存期为7.6个月。结论DOS对不能切除的转移性胃癌患者是安全耐受的，具有较高的转换率和初步疗效。使用已确定的RD的DOS方案的第二阶段试验正在进行中。
PurposeThe aim of this study was to determine the recommended dose (RD) for a docetaxel/oxaliplatin/S-1 (DOS) regimen in patients with unresectable gastric cancer and to preliminarily evaluate its efficacy.MethodsPreviously untreated patients with histologically proven unresectable metastatic gastric cancer were enrolled (n=16). Docetaxel and oxaliplatin were administered intravenously on day 8 and S-1 was administered orally twice a day on days 1-14. Each cycle was repeated every 3 weeks. Dose-limiting toxicities (DLTs) were evaluated during the first treatment cycle. Three dose escalations of DOS were employed in this study: level 1 (50/100/80mg/m(2)), level 2 (50/130/80mg/m(2)), and level 3 (60/130/80mg/m(2)).ResultsAccording to the 3+3 dose-escalating schedule, we determined that the RD and maximum tolerated dose for this regimen were level 1 and level 2, respectively. The DLTs were grade 3 diarrhea and febrile neutropenia. The overall response rate was 78% (7/9) for patients with measurable lesions and consisted of two complete responses and five partial responses. Five patients underwent conversion surgery. The median follow-up time was 19 months with median survival time and progression-free survival being 19.6 months and 7.6 months, respectively.ConclusionsThe results from this study demonstrated the safety and tolerability of DOS in unresectable metastatic gastric cancer patients and revealed promising preliminary efficacy with a high conversion rate. A phase II trial of DOS regimen using the identified RD is ongoing.