口服尿嘧啶替加氟加亚叶酸钙与静脉注射氟尿嘧啶和亚叶酸钙作为辅助化疗用于接受日本D2/D3淋巴结清扫的III期结直肠癌患者的随机III期试验：JCOG0205的最终结果
Randomised phase III trial of adjuvant chemotherapy with oral uracil and tegafur plus leucovorin versus intravenous fluorouracil and levofolinate in patients with stage III colorectal cancer who have undergone Japanese D2/D3 lymph node dissection: final results of JCOG0205.
作者信息
Shimada Yasuhiro, Hamaguchi Tetsuya, Mizusawa Junki, Saito Norio, Kanemitsu Yukihide, Takiguchi Nobuhiro, Ohue Masayuki, Kato Takeshi, Takii Yasumasa, Sato Toshihiko, Tomita Naohiro, Yamaguchi Shigeki, Akaike Makoto, Mishima Hideyuki, Kubo Yoshiro, Nakamura Kenichi, Fukuda Haruhiko, Moriya Yoshihiro
机构信息
National Cancer Center Hospital, Tokyo, Japan.
National Cancer Center Hospital, Tokyo, Japan.
出版信息
Eur J Cancer. 2014 Sep;50(13):2231-40. doi: 10.1016/j.ejca.2014.05.025. Epub 2014 Jun 20.
BACKGROUND
NSABP C-06 demonstrated the non-inferiority of oral adjuvant uracil and tegafur plus leucovorin (UFT/LV) to weekly fluorouracil and folinate (5-FU/LV) with respect to disease-free survival (DFS) for stage II/III colon cancer. This is the first report of JCOG0205, which compared UFT/LV to standard 5-FU/levofolinate (l-LV) for stage III colorectal cancer patients who have undergone Japanese D2/D3 lymph node dissection.
METHODS
Patients were randomised to three courses of 5-FU/l-LV (5-FU 500 mg/m(2), l-LV 250 mg/m(2) on days 1, 8, 15, 22, 29, 36 every 8 weeks) or five courses of UFT/LV (UFT 300 mg m(-2)day(-1), LV 75 mg/day on days 1-28 every 5 weeks). The primary end-point was DFS. The sample size was 1100 determined with one-sided alpha of 0.05, power of 0.78 and non-inferiority margin of hazard ratio of 1.27. This trial is registered with UMIN-CTR (C000000193).
FINDINGS
Between February 2003 and November 2006, 1,101 patients (1092 eligible patients) were randomised to 5-FU/l-LV (n=550) or UFT/LV (n=551). Median age: 61 years, colon/rectum: 67%/33%, number of positive nodes ⩽3/>3: 73%/27%, stage IIIa/IIIb: 75%/25%. The hazard ratio of DFS was 1.02 (91.3% confidence interval, 0.84-1.23), demonstrating the non-inferiority of UFT/LV (P=0.0236). Five-year overall survival (87.5%) was higher than that in NSABP C-06 (69.6%). Grade 3/4 toxicities were 8.4% neutropenia in 5-FU/l-LV and 8.7% alanine aminotransferase elevation in UFT/LV, respectively. The incidences of diarrhoea (9.6% versus 8.5%) and anorexia (4.0% versus 3.7%) were similar between the two arms. No treatment-related deaths were reported.
INTERPRETATION
Adjuvant UFT/LV is non-inferior to standard 5-FU/l-LV with respect to DFS. UFT/LV should be an oral treatment option for patients with stage III colon cancer who have undergone Japanese D2/D3 lymph node dissection.
背景
NSABP C - 06研究表明，对于II/III期结肠癌患者，口服辅助药物尿嘧啶替加氟加亚亚亚（UFT/LV）在无病生存期（DFS）方面不劣于每周使用氟尿嘧啶和亚叶酸（5 - FU/LV）。这是JCOG0205的首次报告，该研究比较了UFT/LV与标准5 - FU/亚叶酸钙（l - LV）对接受日本D2/D3淋巴结清扫术的III期结直肠癌患者的疗效。
方法
患者被随机分为三组，接受三个疗程的5 - FU/l - LV（5 - FU 500 mg/m²，l - LV 250 mg/m²，在第1、8、15、22、29、36天，每8周一次）或五个疗程的UFT/LV（UFT 300 mg m⁻²天⁻¹，LV 75 mg/天，在第1 - 28天，每5周一次）。主要终点是DFS。样本量为1100，单侧α为0.05，检验效能为0.78，非劣效性界值为风险比1.27。该试验已在UMIN - CTR注册（C000000193）。
研究结果
2003年2月至2006年11月，1101例患者（1092例符合条件）被随机分为5 - FU/l - LV组（n = 550）或UFT/LV组（n = 551）。中位年龄：61岁，结肠癌/直肠癌：67%/33%，阳性淋巴结数≤3/＞3：73%/27%，IIIa/IIIb期：75%/25%。DFS的风险比为1.02（91.3%置信区间，0.84 - 1.23），表明UFT/LV不劣于5 - FU/l - LV（P = 0.0236）。五年总生存率（87.5%）高于NSABP C - 06研究中的（69.6%）。3/4级毒性反应方面，5 - FU/l - LV组中性粒细胞减少为8.4%，UFT/LV组丙氨酸转氨酶升高为8.7%。两组腹泻（9.6%对8.5%）和厌食（4.0%对3.7%）的发生率相似。未报告与治疗相关的死亡病例。
解读
辅助使用UFT/LV在DFS方面不劣于标准的5 - FU/l - LV。对于接受日本D2/D3淋巴结清扫术的III期结肠癌患者，UFT/LV应是一种口服治疗选择。
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