Qian Shi, Axel Grothey, Brian M. Bot, and Daniel J. Sargent, North Central Cancer Treatment Group, Mayo Clinic, Rochester, MN; Thierry Andre, Hôpital Saint Antoine, Paris, France; Greg Yothers and Michael J. O'Connell, National Surgical Adjuvant Breast and Bowel Project, Pittsburgh; Daniel G. Haller, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA; Stanley R. Hamilton, University of Texas MD Anderson Cancer Center, Houston, TX; Brian M. Bot, Sage Bionetworks; Jacqueline K. Benedetti, Southwest Oncology Group Statistical Center, Seattle, WA; Eric Van Cutsem, University Hospital Gasthuisberg, Gasthuisberg, Belgium; and Chris Twelves, St James's University Hospital, Leeds, United Kingdom.
J Clin Oncol. 2013 Oct 10;31(29):3656-63. doi: 10.1200/JCO.2013.49.4344. Epub 2013 Aug 26.
With improved patient care, better diagnosis, and more treatment options after tumor recurrence, outcomes after fluorouracil (FU) -based treatment are expected to have improved over time in early-stage colon cancer. Data from 18,449 patients enrolled onto 21 phase III trials conducted from 1978 to 2002 were evaluated for potential differences in time to recurrence (TTR), time from recurrence to death (TRD), and overall survival (OS) with regard to FU-based adjuvant regimens.
Trials were predefined as old versus newer era using initial accrual before or after 1995. Outcomes were compared between patients enrolled onto old- or newer-era trials, stratified by stage.
Within the first 3 years, recurrence rates were lower in newer- versus old-era trials for patients with stage II disease, with no differences among those with stage III disease. Both TRD and OS were significantly longer in newer-era trials overall and within each stage. The lymph node (LN) ratio (ie, number of positive nodes divided by total nodes harvested) in those with stage III disease declined over time. TTR improved slightly, with larger number of LNs examined in both stages.
Improved TRD in newer trials supports the premise that more aggressive intervention (oxaliplatin- and irinotecan-based chemotherapy and/or surgery for recurrent disease) improves OS for patients previously treated in the adjuvant setting. Lower recurrence rates with identical treatments in those with stage II disease enrolled onto newer-era trials reflect stage migration over time, calling into question historical data related to the benefit of FU-based adjuvant therapy in such patients.
由于肿瘤复发后的患者护理得到改善，诊断更为准确，治疗选择更多，因此在早期结肠癌中，氟尿嘧啶（FU）为基础的治疗后结果预计会随着时间的推移而改善。评估了 1978 年至 2002 年间进行的 21 项 III 期试验中 18449 名患者的数据，以评估 FU 为基础的辅助治疗方案在复发时间（TTR）、复发后至死亡时间（TRD）和总生存（OS）方面的潜在差异。
根据 1995 年前或后首次入组的时间，将试验预设为旧时代和新时代。将入组到旧时代或新时代试验的患者进行分层，根据分期比较结局。
在最初的 3 年内，对于 II 期疾病患者，在新时代试验中复发率低于旧时代试验，而对于 III 期疾病患者，两者之间无差异。总体而言和每个分期内，新时代试验的 TRD 和 OS 都明显更长。对于 III 期疾病患者，淋巴结（LN）比值（即阳性淋巴结数除以总淋巴结数）随时间下降。TTR 略有改善，两个分期的检查 LN 数量均增加。
在新时代试验中，TRD 的改善支持了这样的前提，即更积极的干预（奥沙利铂和伊立替康为基础的化疗和/或复发性疾病手术）改善了既往辅助治疗患者的 OS。在入组新时代试验的 II 期疾病患者中，相同治疗下的复发率降低，这反映了随着时间的推移分期迁移，对与 FU 为基础辅助治疗在这些患者中获益相关的历史数据提出了质疑。
