Survival after adjuvant 5-FU treatment for stage III colon cancer in hereditary nonpolyposis colorectal cancer
Survival after adjuvant 5-FU treatment for stage III colon cancer in hereditary nonpolyposis colorectal cancer
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DOI：
10.1002/ijc.11712
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发表时间：
2004-04-10
影响因子：
6.4
通讯作者：
Vasen, HFA
中科院分区：
文献类型：
--
作者：
Cappel, WHDN;Meulenbeld, HJ;Vasen, HFA
体外研究表明，错配修复（MMR）系统缺陷降低5-氟尿嘧啶的细胞毒性。遗传性非息肉病性结直肠癌（HNPCC）中的结肠癌（CC）是由于MMR基因功能障碍导致微卫星不稳定性（MSI）。关于5-氟尿嘧啶（5-FU）在MSI高肿瘤中的疗效的临床研究是矛盾的。在一项回顾性研究中，我们比较了接受和不接受5-FU辅助治疗的HNPCC家族III期CC受试者的生存率。使用荷兰HNPCC家庭登记处。III期CC的辅助化疗信息来自突变家族和/或符合AMS标准或高度怀疑HNPCC的受试者。计算CC特异性存活率。测量观察时间直至死亡日期、第二次主要CC日期或直至研究结束日期，即，2001年6月1日。通过Kaplan-Meier生存分析进行统计学分析。共纳入92例III期CC受试者。其中28例（17例男性）接受了5-FU辅助治疗。中位随访时间为4年（范围：1-17年）; 8例受试者死于CC。5年生存率为70%（95%CI：49-90）。64例受试者（36例男性）未接受辅助治疗。中位随访时间为6年（范围：0-23年）。其中20人死于CC。该组的5年生存率也为70%（95%CI：59-83）。迄今为止，选择CC患者进行5-FU治疗是基于肿瘤的分期而不是生物学。在我们的研究中，接受和不接受5-FU辅助治疗的受试者的5年生存率没有差异。需要进一步研究以阐明MSI在5-FU治疗HNPCC中MSI-H肿瘤中的作用。(C)2004 Wiley-Liss，Inc.
In vitro studies suggest that a deficient mismatch repair (MMR) system-reduces 5-Fluorouracil cytotoxicity. Colon cancer (CC) in hereditary nonpolyposis colorectal cancer (HNPCC) is due to a dysfunctioning MMR gene that leads to microsatellite instability (MSI). Clinical studies on the efficacy of 5-Fluorouracil (5-FU) in MSI high tumours are contradictory. In a retrospective study, we compared the survival of subjects with stage III CC from HNPCC families that were treated with and without adjuvant 5-FU. The Dutch HNPCC family registry was used. Information on adjuvant chemotherapy for stage III CC was obtained from subjects of families with a mutation and/or who fulfilled the AMS criteria or who were strongly suspicious for HNPCC. CC specific survival was calculated. Observation time was measured either until the date of death, date of a second primary CC or until the closing date of the study, i.e., June 1, 2001. Statistical analysis was done by Kaplan-Meier survival analysis. A total of 92 subjects with stage III CC were included. Twenty-eight of them (17 males) had adjuvant treatment with 5-FU. The median follow-up was 4 (range: 1-17) years; 8 subjects died of CC. The 5-year survival was 70% (95% Cl: 49-90). Sixty-four subjects (36 males) did not have adjuvant therapy. Their median follow-up was 6 (range: 0-23) years. Twenty of them died of CC. The 5-year survival in this group was also 70% (95% CI: 59-83). To date, the selection of patients with CC for 5-FU treatment is based on the stage rather than the biology of the tumour. In our study, the 5-year survival of subjects treated with and without adjuvant 5-FU did not differ. Further studies are necessary to elucidate the role of MSI in 5-FU treatment of MSI-H tumours in HNPCC. (C) 2004 Wiley-Liss, Inc.