Ishigami Hironori, Kitayama Joji, Otani Kensuke, Kamei Takao, Soma Daisuke, Miyato Hideyo, Yamashita Hiroharu, Hidemura Akio, Kaisaki Shoichi, Nagawa Hirokazu
Department of Surgical Oncology, University of Tokyo, Tokyo, Japan.
Oncology. 2009;76(5):311-4. doi: 10.1159/000209277. Epub 2009 Mar 20.
A dose-escalation study of weekly intraperitoneal paclitaxel (PTX) combined with S-1 and intravenous PTX was performed to determine the maximum-tolerated dose (MTD) and recommended dose (RD) in gastric cancer patients.
Nine gastric cancer patients with peritoneal dissemination and/or cancer cells on peritoneal cytology were enrolled. PTX was administered intravenously on days 1 and 8 at a fixed dose of 50 mg/m(2), and intraperitoneally with an initial dose of 20 mg/m(2), stepped up to 30 or 40 mg/m(2). S-1 was administered at a fixed dose of 80 mg/m(2)/day for 14 consecutive days, followed by 7 days of rest. A pharmacokinetic study of PTX was also performed.
The MTD was determined to be 30 mg/m(2), as 2 of 3 patients developed dose-limiting toxicities, grade 3 febrile neutropenia and diarrhea. Therefore, the RD was determined to be 20 mg/m(2). The intraperitoneal and serum PTX concentration remained effective for over 72 and 48 h, respectively.
Combined chemotherapy of S-1 plus weekly intravenous and intraperitoneal PTX was shown to be a safe regimen that should be further explored in clinical trials.
开展一项每周腹腔注射紫杉醇（PTX）联合S-1及静脉注射PTX的剂量递增研究，以确定胃癌患者的最大耐受剂量（MTD）和推荐剂量（RD）。
纳入9例有腹膜播散和/或腹腔细胞学检查发现癌细胞的胃癌患者。PTX于第1天和第8天静脉注射，固定剂量为50mg/m²，腹腔注射初始剂量为20mg/m²，逐步增至30或40mg/m²。S-1以80mg/m²/天的固定剂量连续给药14天，随后休息7天。还进行了PTX的药代动力学研究。
确定MTD为30mg/m²，因为3例患者中有2例出现剂量限制性毒性，即3级发热性中性粒细胞减少和腹泻。因此，确定RD为20mg/m²。腹腔内和血清PTX浓度分别在72小时和48小时以上保持有效。
S-1联合每周静脉和腹腔注射PTX的联合化疗被证明是一种安全的方案，应在临床试验中进一步探索。
