Clin Color Cancer：新型血液检测技术或可帮助结直肠癌患者避免不必要的药物副作用

  来自曼彻斯特大学的研究人员早期研究发现，血液检测手段或许可以被用于鉴别肠癌（结直肠癌）患者是否可以通过加大剂量化疗中获取更多益处，结直肠癌是欧洲第二大引发人类死亡的癌症，临床研究者常用组合型的化疗制剂来对其进行治疗，而利用额外的药物往往也可以改善患者的预后情况，然而多种药物的方法则会增加药物的副作用，比如脱发、白细胞数量降低、腹泻及周围神经系统受损。
  于是这项研究中，曼彻斯特大学的科学家们开发出了一种新型的血液检测技术，其或许可以对患者血液中的肿瘤细胞进行计数，以此作为预测个体获益的方法；研究者Caroline Dive表示，我们非常感兴趣来检测从病人肿瘤及血液循环中“跑出去”的癌症细胞，本文中我们想去观察是否血液样本中的肿瘤细胞数量和病人对高强度化疗产生的反应之间存在一定关联。
  文章中，研究者观察了接受四种药物联合疗法的进行性结直肠癌患者的治疗情况，结果发现，相比那些机体血液样本中循环肿瘤细胞类型较少的患者，血液样本中存在三种或更多循环肿瘤细胞的病人往往总体生存率较低，携带多种循环肿瘤细胞的患者在治疗前或许可以从密集高强度的治疗体系中获取更多的利益。
  研究者表示，初期研究结果显示，这种新型的血液检测技术对于病人进行疗法的选择非常有用，但后期还需要大量的临床试验来进行更深层次的验证；本文研究对于开发更多的新型个体化结直肠癌疗法来治疗癌症患者使其获益非常重要，其也为推动癌症疗法的革新带来了一定的帮助。（转化医学网360zhyx.com）
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转化医学网推荐的原文摘要：

Circulating Tumor Cell Enumeration in a Phase II Trial of a Four-Drug Regimen in Advanced Colorectal Cancer
Clinical Colorectal Cancer      doi:10.1016/j.clcc.2014.12.006
Matthew G. Krebs, Andrew G. Renehan, Alison Backen, Simon Gollins, Ian Chau, Jurjees Hasan, Juan W. Valle, Karen Morris, Janette Beech, Linda Ashcroft, Mark P. Saunders, Caroline Dive
Background
Multidrug regimens are active against advanced colorectal cancer (ACRC). However, the increased toxicity requires the use of biomarkers to select the patients who will derive the most benefit. We assessed circulating tumor cells (CTCs) as a prognostic biomarker in patients treated with a 4-drug regimen.

Patients and Methods
A single-arm phase II trial (Erbitux Study of CPT11, Oxaliplatin, UFToral Targeted-therapy [eSCOUT]) was undertaken in patients with previously untreated KRAS wild-type ACRC using a regimen of irinotecan, oxaliplatin, and tegafur-uracil with leucovorin and cetuximab. Baseline CTCs were enumerated using CellSearch. The endpoints were an objective response rate (ORR) and overall survival (OS). We modeled our results and compared them with those modeled for the capecitabine, oxaliplatin, bevacizumab +/- cetuximab (CAIRO2) trial, stratifying patients a priori into low (< 3) and high (≥ 3) CTC groups.

Results
For 48 eligible patients, the best ORR from the 4-drug regimen was 71%, with a disease control rate of 98%. The median OS for patients with a high and low CTC count was 18.7 and 22.3 months (log-rank test, P = .038), respectively. In our modeled data, for patients with a low CTC count, no differences were found between the median OS in the eSCOUT trial and that in the CAIRO2 trial (22.2 vs. 22.0 months). However, for the high CTC group, a clinically relevant improvement was seen in median OS (eSCOUT vs. CAIRO2, 18.7 vs. 13.7 months; P = .001).

Conclusion
These data are hypothesis generating—for patients with ACRC, stratification by CTC count can identify those who might benefit the most from an intensive 4-drug regimen, avoiding high-toxicity regimens in low CTC groups. This hypothesis warrants validation in a phase III biomarker-driven trial.