Sudo Kentaro, Yamaguchi Taketo, Ishihara Takeshi, Nakamura Kazuyoshi, Shirai Yoshihiko, Nakagawa Akihiko, Kawakami Hiroyuki, Uno Takashi, Ito Hisao, Saisho Hiromitsu
Department of Medicine and Clinical Oncology, Graduate School of Medicine, Chiba University, Inohana, Chiba, Japan.
Int J Radiat Oncol Biol Phys. 2007 Jan 1;67(1):219-24. doi: 10.1016/j.ijrobp.2006.08.046.
The primary objective of this study was to determine the maximum-tolerated dose (MTD) of S-1, an oral fluoropyrimidine derivative, with concurrent radiotherapy in patients with unresectable locally advanced pancreatic cancer.
Patients with histopathologically proven, unresectable, locally advanced pancreatic cancer were eligible. Radiotherapy was delivered in 1.8 Gy daily fractions to a total dose of 50.4 Gy over 5.5 weeks. S-1 was administered orally twice a day from Day 1 to 14 and 22 to 35 at escalating doses from 60 to 80 mg/m(2)/day.
Sixteen patients were enrolled in this study. Three patients received S-1 at 60 mg/m(2)/day, 3 at 70 mg/m(2)/day, and 10 at 80 mg/m(2)/day. Though 1 patient at the final dose level (80 mg/m(2)/day) experienced a dose limiting toxicity (biliary infection with Grade 3 neutropenia), the MTD was not reached in this study. The most common toxicities were anorexia and leukocytopenia, with Grade 3 toxicity occurring in 31% and 6.3% of the patients, respectively.
The recommended dose of S-1 with concurrent radiotherapy was determined to be 80 mg/m(2)/day from Day 1 to 14 and 22 to 35 in patients with locally advanced pancreatic cancer. Oral S-1 and radiotherapy is well tolerated and feasible and should be further investigated.
本研究的主要目的是确定口服氟嘧啶衍生物S-1与同步放疗联合应用于不可切除的局部晚期胰腺癌患者时的最大耐受剂量（MTD）。
组织病理学确诊为不可切除的局部晚期胰腺癌患者符合入组条件。放疗采用每日1.8 Gy分次照射，在5.5周内总剂量达50.4 Gy。S-1从第1天至14天以及第22天至35天每天口服两次，剂量从60 mg/m²/天逐步递增至80 mg/m²/天。
本研究共纳入16例患者。3例患者接受60 mg/m²/天的S-1治疗，3例接受70 mg/m²/天，10例接受80 mg/m²/天。尽管最终剂量水平（80 mg/m²/天）的1例患者出现了剂量限制性毒性（3级中性粒细胞减少伴胆道感染），但本研究未达到MTD。最常见的毒性反应是厌食和白细胞减少，3级毒性反应分别发生在31%和6.3%的患者中。
对于局部晚期胰腺癌患者，推荐S-1与同步放疗联合应用的剂量为第1天至14天以及第22天至35天每天80 mg/m²。口服S-1与放疗耐受性良好且可行，应进一步研究。
