Phase I/II study of a combination of capecitabine, cisplatin, and intraperitoneal docetaxel (XP ID) in advanced gastric cancer patients with peritoneal metastasis
Phase I/II study of a combination of capecitabine, cisplatin, and intraperitoneal docetaxel (XP ID) in advanced gastric cancer patients with peritoneal metastasis
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DOI：
10.1007/s10120-017-0710-0
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发表时间：
2017-11-01
期刊：
影响因子：
7.4
通讯作者：
Kang, Yoon-Koo
中科院分区：
文献类型：
--
作者：
Cho, Hyungwoo;Ryu, Min-Hee;Kang, Yoon-Koo
本研究旨在确定多西他赛（ID）腹腔内联合全身卡培他滨和顺铂（XP）的推荐剂量（RD），并评价其在RD时治疗伴有腹膜转移的晚期胃癌（AGC）患者的疗效和安全性。方法AGC合并腹膜转移患者接受XP ID治疗，其中卡培他滨937.5 mg/m(2)，每日2次，第1天静脉注射顺铂60mg /m(2)，第1天腹腔注射多西他赛3种不同剂量(60mg /m(2), 80 mg/m(2)，每3周一次。在第一阶段的研究中，采用标准的3 + 3方法确定XP ID的RD。在II期研究中，患者接受了XP ID的RD。在I期研究中，选择ID 100 mg/m(2)作为RD， 6例患者中有1例出现剂量限制性毒性（肠梗阻）。入选II期研究的39例AGC患者接受了XP ID的RD。中位无进展生存期为11.0个月（95% CI 6.9-15.1），中位总生存期为15.1个月（95% CI 9.1-21.1）。最常见的3/4级不良事件是中性粒细胞减少（38.6%）和腹痛（30.8%）。在治疗周期的后期，腹痛的发生率逐渐增加。结论：我们的研究表明，XP ID对腹膜转移的AGC患者有效，毒性可控。由于腹痛的累积发生率可能与ID对肠道的刺激有关，因此可能有必要调整剂量。
Background This study was conducted to determine the recommended dose (RD) of intraperitoneal docetaxel (ID) in combination with systemic capecitabine and cisplatin (XP) and to evaluate its efficacy and safety at the RD in advanced gastric cancer (AGC) patients with peritoneal metastasis.Methods AGC patients with peritoneal metastasis received XP ID, which consists of 937.5 mg/m(2) of capecitabine twice daily on days 1-14, 60 mg/m(2) of intravenous cisplatin on day 1, and intraperitoneal docetaxel at 3 different dose levels (60, 80, or 100 mg/m(2)) on day 1, every 3 weeks. In the phase I study, the standard 3 + 3 method was used to determine the RD of XP ID. In the phase II study, patients received RD of XP ID.Results In the phase I study, ID 100 mg/m(2) was chosen as the RD, with one dose-limiting toxicity (ileus) out of six patients. The 39 AGC patients enrolled in the phase II study received the RD of XP ID. The median progressionfree survival was 11.0 months (95% CI 6.9-15.1), and median overall survival was 15.1 months (95% CI 9.1-21.1). The most frequent grade 3/4 adverse events were neutropenia (38.6%) and abdominal pain (30.8%). The incidence of abdominal pain cumulatively increased in the later treatment cycles.Conclusions Our study indicated that XP ID was effective, with manageable toxicities, in AGC patients with peritoneal metastasis. As the cumulative incidence of abdominal pain was probably related to bowel irritation by ID, it might be necessary to modify the dose.