Is postoperative adjuvant chemotherapy useful for gallbladder carcinoma? A phase III multicenter prospective randomized controlled trial in patients with resected pancreaticobiliary carcinoma
Is postoperative adjuvant chemotherapy useful for gallbladder carcinoma? A phase III multicenter prospective randomized controlled trial in patients with resected pancreaticobiliary carcinoma
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DOI：
10.1002/cncr.10831
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发表时间：
2002-10-15
期刊：
影响因子：
6.2
通讯作者：
Nakayama, T
中科院分区：
文献类型：
--
作者：
Takada, T;Amano, H;Nakayama, T
背景资料。据作者所知，胰胆管癌术后辅助化疗的意义尚未阐明。一项随机对照研究评估了术后应用丝裂霉素C(MMC)和5-氟尿嘧啶(5-FU)(MF组)与单纯手术组(对照组)对每种特定疾病(包括胰腺、胆囊癌、胆管或Vater癌壶腹)的生存率和无病生存率(DFS)的影响。方法1986年4月至1992年6月，共有508例胰腺、胆管、胆囊癌切除患者，Vater壶腹癌56例，随机分为治疗组和对照组。MMC组静脉滴注MMC(6 mg/m(2))。手术时和5-FU(310 mg/m(2)静脉注射)术后第1、3周连续治疗5d，术后第5周开始每日口服5-FU(100 mg/m(2))，直至复发。结果：排除不合格病例后，共纳入胰腺癌158例(MF组81例，对照组77例)，胆管癌118例(MF组58例，对照组60例)，胆囊癌112例(MF组69例，对照组43例)，Vater壶腹癌48例(MF组24例，对照组24例)。MF治疗的依从性良好(>；80%)。MF组胆囊癌患者的5年生存率(26.0%)明显高于对照组(14.4%)(P=0.0367)。同样，MF组胆囊癌患者的5年DFS率为20.3%，显著高于对照组11.6%的DFS率(P=0.0210)。只有胆囊癌患者的体重与对照组相比有显著改善。有胰腺癌、胆管癌和壶腹癌的患者之间的5年生存率和5年DFS率没有明显差异。多因素分析显示，MF组的死亡率(风险比为0.654；P=0.0825)和复发风险(风险比为0.626；P=0.0589)较低。最常见的不良反应是厌食、恶心/呕吐、口腔炎和白细胞减少，这些都没有严重的报道。结论：目前的研究结果表明，接受非根治性切除的胆囊癌患者可以从全身化疗中获益。然而，必须为胰腺癌、胆管癌或瓦特壶腹癌患者开发替代治疗方法。(C)2002年美国癌症协会。
BACKGROUND. To the authors' knowledge, the significance of postoperative adjuvant chemotherapy in pancreaticobiliary carcinoma has not yet been clarified. A randomized controlled study evaluated the effect of postoperative adjuvant therapy with mitomycin C (MMC) and 5-fluorouracil (5-FU) (MF arm) versus surgery alone (control arm) on survival and disease-free survival (DFS) for each specific disease comprising resected pancreaticobiliary carcinoma (pancreatic, gallbladder, bile duct, or ampulla of Vater carcinoma) separately.METHODS. Between April 1986 and June 1992, a total of 508 patients with resected pancreatic (n = 173), bile duct (n = 139), gallbladder (n = 140), or ampulla of Vater (n = 56) carcinomas were allocated randomly to either the MF group or the control group. The MF group received MMC (6 mg/m(2) intravenously [i.v.]) at the time of surgery and 5-FU (310 mg/m(2) i.v.) in 2 courses of treatment for 5 consecutive days during postoperative Weeks 1 and 3, followed by 5-FU (100 mg/m(2)orally) daily from postoperative Week 5 until disease recurrence. All patients were followed for 5 years.RESULTS. After ineligible patients were excluded, 158 patients with pancreatic carcinoma (81 in the MF group and 77 in the control group), 118 patients with bile duct carcinoma (58 in the MF group and 60 in the control group), 112 patients with gallbladder carcinoma (69 in the MF group and 43 in the control group), and 48 patients with carcinoma of the ampulla of Vater (24 in the MF group and 24 in the control group) were evaluated. Good compliance (> 80%) was achieved with MF treatment. The 5-year survival rate in gallbladder carcinoma patients was significantly better in the MF group (26.0%) compared with the control group (14.4%) (P = 0.0367). Similarly, the 5-year DFS rate of patients with gallbladder carcinoma was 20.3% in the MF group, which was significantly higher than the 11.6% DFS rate reported in the control group (P = 0.0210). Significant improvement in body weight compared with the control was observed only in patients with gallbladder carcinoma. There were no apparent differences in 5-year survival and 5-year DFS rates between patients with pancreatic, bile duct, or ampulla of Vater carcinomas. Multivariate analyses demonstrated a tendency for the MF group to have a lower risk of mortality (risk ratio of 0.654; P = 0.0825) and recurrence (risk ratio of 0.626; P = 0.0589). The most commonly reported adverse drug reactions were anorexia, nausea/emesis, stomatitis, and leukopenia, none of which were noted to be serious.CONCLUSIONS. The results of the current study indicate that gallbladder carcinoma patients who undergo noncurative resections may derive some benefit from systemic chemotherapy. However, alternative modalities must be developed for patients with carcinomas of the pancreas, bile duct, or ampulla of Vater. (C) 2002 American Cancer Society.