Tanno Satoshi, Nakano Yasuhiro, Osanai Manabu, Koizumi Kazuya, Izawa Tsutomu, Habiro Atsuya, Mizukami Yusuke, Yanagawa Nobuyuki, Fujii Tsuneshi, Okumura Toshikatsu, Kohgo Yutaka
Third Department of Internal Medicine, Asahikawa Medical College, Asahikawa, Japan.
Chemotherapy. 2006;52(2):98-102. doi: 10.1159/000092372. Epub 2006 Mar 27.
Gemcitabine is widely accepted as the first-line agent for advanced pancreatic cancer. The antitumor cell activity of gemcitabine is higher when administered after 5-fluorouracil (5-FU) rather than before 5-FU in an in vitro study. The present study was conducted to define the maximum tolerated dose and dose-limiting toxicity associated with an oral fluoropyrimidine prodrug that combines uracil and tegafur (UFT), given prior to weekly intravenous gemcitabine in patients with advanced pancreatic cancer.
Over a 21-day cycle, gemcitabine was given intravenously over 30 min on days 8 and 15, while UFT was given orally from days 1 to 14. The dose of UFT used was 400 mg per day, given as two doses. The dose of gemcitabine was escalated in a stepwise fashion from 800 (level 1, n = 3) to 900 mg/m2 (level 2, n = 6) and then to 1,000 mg/m2 (level 3, n = 3), such that totally 12 patients received the combination chemotherapy.
During the first cycle, grade 3 leukopenia was observed in 2 patients at dose level 1. Only 1 patient treated at dose level 2 experienced dose-limiting toxicity (grade 3 elevated transaminase), including additional patients treated at this dose level. No grade 3/4 toxicities occurred in patients treated at dose level 3. A significant response was observed in 1 out of 12 patients (8.3%). Seven patients (58.3%) had stable disease, while 4 patients (33.3%) showed disease progression.
The combination chemotherapy of oral UFT and gemcitabine was convenient, well tolerated and may benefit patients with advanced pancreatic cancer. Doses recommended for further study of this schedule are gemcitabine 1,000 mg/m2 and UFT 400 mg/day.
吉西他滨被广泛认为是晚期胰腺癌的一线治疗药物。在一项体外研究中，吉西他滨在5-氟尿嘧啶（5-FU）之后给药时的抗肿瘤细胞活性高于在5-FU之前给药时。本研究旨在确定在晚期胰腺癌患者中，在每周静脉注射吉西他滨之前给予一种将尿嘧啶和替加氟（UFT）联合的口服氟嘧啶前体药物时的最大耐受剂量和剂量限制性毒性。
在一个21天的周期内，吉西他滨于第8天和第15天静脉滴注30分钟，而UFT于第1天至第14天口服。所用UFT的剂量为每天400毫克，分两次给药。吉西他滨的剂量从800毫克/平方米（1级，n = 3）逐步递增至900毫克/平方米（2级，n = 6），然后至1000毫克/平方米（3级，n = 3），共有12例患者接受了联合化疗。
在第一个周期中，1级剂量水平的2例患者出现了3级白细胞减少。在2级剂量水平接受治疗的患者中，只有1例经历了剂量限制性毒性（3级转氨酶升高），包括在该剂量水平接受治疗的其他患者。在3级剂量水平接受治疗的患者中未发生3/4级毒性反应。12例患者中有1例（8.3%）出现显著缓解。7例患者（58.3%）病情稳定，而4例患者（33.3%）疾病进展。
口服UFT与吉西他滨联合化疗方便、耐受性良好，可能使晚期胰腺癌患者获益。该方案进一步研究推荐的剂量为吉西他滨1000毫克/平方米和UFT每天400毫克。
