Ikeda M, Okusaka T, Ito Y, Ueno H, Morizane C, Furuse J, Ishii H, Kawashima M, Kagami Y, Ikeda H
Hepatobiliary and Pancreatic Oncology Division, National Cancer Center Hospital, Tokyo, Japan.
Br J Cancer. 2007 Jun 4;96(11):1650-5. doi: 10.1038/sj.bjc.6603788. Epub 2007 May 29.
This study investigated the maximum tolerated dose of S-1 based on the frequency of its dose-limiting toxicities (DLT) with concurrent radiotherapy in patients with locally advanced pancreatic cancer. S-1 was administered orally at escalating doses from 50 to 80 mg m(-2) b.i.d. on the day of irradiation during radiotherapy. Radiation therapy was delivered through four fields as a total dose of 50.4 Gy in 28 fractions over 5.5 weeks, and no prophylactic nodal irradiation was given. Twenty-one patients (50 three; 60 five; 70 six; 80 mg m(-2) seven patients) were enrolled in this trial. At a dose of 70 mg m(-2) S-1, two of six patients demonstrated DLT involving grade 3 nausea and vomiting and grade 3 haemorrhagic gastritis, whereas no patients at doses other than 70 mg m(-2) demonstrated any sign of DLT. Among the 21 enrolled patients, four (19.0%) showed a partial response. The median progression-free survival time and median survival time for the patients overall were 8.9 and 11.0 months, respectively. The recommended dose of S-1 therapy with concurrent radiotherapy is 80 mg m(-2) day(-1). A multi-institutional phase II trial of this regimen in patients with locally advanced pancreatic cancer is now underway.
本研究基于剂量限制毒性（DLT）的发生频率，调查了局部晚期胰腺癌患者在同步放疗时S-1的最大耐受剂量。在放疗期间的照射日，S-1以50至80 mg m(-2) bid的递增剂量口服给药。放射治疗通过四个野进行，总剂量为50.4 Gy，分28次在5.5周内给予，未进行预防性淋巴结照射。21例患者（50 mg m(-2) 3例；60 mg m(-2) 5例；70 mg m(-2) 6例；80 mg m(-2) 7例）纳入本试验。在S-1剂量为70 mg m(-2)时，6例患者中有2例出现DLT，包括3级恶心呕吐和3级出血性胃炎，而70 mg m(-2)以外剂量的患者未出现任何DLT迹象。在21例纳入患者中，4例（19.0%）显示部分缓解。患者总体的中位无进展生存期和中位生存期分别为8.9个月和11.0个月。同步放疗时S-1治疗的推荐剂量为80 mg m(-2) 每日(-1)。目前正在进行一项针对局部晚期胰腺癌患者的该方案多机构II期试验。
