Katayose Yu, Rikiyama Toshiki, Motoi Fuyuhiko, Yamamoto Kuniharu, Yoshida Hiroshi, Morikawa Takanori, Hayashi Hiroki, Kanno Atsushi, Hirota Morihisa, Satoh Kennichi, Ariga Hisanori, Suzuki Masaki, Ohyauchi Motoki, Kondo Yutaka, Ikeya Shinichi, Ogawa Yoshihiro, Shimosegawa Tooru, Egawa Shinichi, Unno Michiaki
Department of Surgery, Tohoku University Graduate School of Medicine, Sendai, Japan.
Hepatogastroenterology. 2011 Nov-Dec;58(112):1866-72. doi: 10.5754/hge10106.
BACKGROUND/AIMS: The feasibility of neoadjuvant chemoradiation therapy for cholangiocarcinoma, followed by conventional resection, has not been determined yet. Here, a phase I study of neoadjuvant chemoradiation therapy, named NACRAC, was performed to determine the maximum tolerated dose (MTD) and the recommended dose (RD) of gemcitabine when combined with external beam radiation therapy for resectable cholangiocarcinoma.
From August 2007 to June 2008, 12 patients provided informed consent. Preoperative radiation was administered in 1.8Gy daily fractions up to a total dose of 45Gy. Gemcitabine was administered at day 1 and 8 every three weeks. The initial dose of gemcitabine was started from 400mg/m2.
One patient was not able to start treatment because of bleeding caused by a duodenal ulcer and cholangitis. At 800mg/m2 of gemcitabine, one patient out of three failed to complete the treatment because of Grade 3 hematological toxicity. In another three cases of 800mg/m2, the second case could not complete the treatment because of cholangitis. Then, 600mg/m2 was determined to be the MTD, and the RD dose decided as 600mg/m2.
The RD of gemcitabine in NACRAC study was determined to be 600mg/m2. NACRAC study should proceed to a phase II trial to evaluate the effectiveness.
背景/目的：新辅助放化疗联合传统手术治疗胆管癌的可行性尚未确定。在此，开展了一项名为NACRAC的新辅助放化疗I期研究，以确定吉西他滨与外照射放疗联合用于可切除胆管癌时的最大耐受剂量（MTD）和推荐剂量（RD）。
2007年8月至2008年6月，12例患者签署了知情同意书。术前放疗采用每日1.8Gy分次照射，总剂量达45Gy。吉西他滨每三周的第1天和第8天给药。吉西他滨的初始剂量从400mg/m²开始。
1例患者因十二指肠溃疡出血和胆管炎无法开始治疗。在吉西他滨剂量为800mg/m²的3例患者中，1例因3级血液学毒性未能完成治疗。在另外3例800mg/m²的患者中，第2例因胆管炎无法完成治疗。随后，确定600mg/m²为MTD，RD剂量定为600mg/m²。
NACRAC研究中吉西他滨的RD确定为600mg/m²。NACRAC研究应进入II期试验以评估疗效。
