Curr Oncol. 2006 Oct;13(5):173-84. doi: 10.3747/co.v13i5.99.
What is the role of oxaliplatin combined with 5-fluorouracil (5-fu) and folinic acid (fa) in the first- and second-line treatment of advanced (unresectable locally advanced or metastatic) colorectal cancer?
Evidence was selected and reviewed by two members of the Gastrointestinal Cancer Disease Site Group (gi dsg) of Cancer Care Ontario's Program in Evidence-Based Care (pebc) and by a methodologist. The resulting practice guideline report has been reviewed and approved by the gi dsg, which comprises medical and radiation oncologists, surgeons, a pathologist, and patient representatives. External review by Ontario practitioners was obtained through a mailed survey. Final approval of the original guideline report was obtained from the Practice Guidelines Coordinating Committee.
Outcomes of interest were 1-year survival, response rates, and quality of life.
The medline, cancerlit, embase, Guidelines International Network, and Cochrane Library databases were systematically searched for relevant studies. Recommendations were formed based on the evidence reviewed. Through a survey, these recommendations were appraised by Ontario clinicians; the recommendations were then revised by the gi dsg. The systematic review and modified recommendations were approved by a review body within pebc.
The literature review found twenty-one randomized controlled trials and two meta-analyses. Evidence on first-line treatment found infusional 5-fu/fa/oxaliplatin (folfox) to be superior to bolus 5-fu/fa/irinotecan (ifl) for rates of median survival and tumour response, with lower incidences of most adverse effects except peripheral neuropathy. For second-line treatment after fluoropyrimidine monotherapy, folfox is a reasonable alternative for patients with contraindications to second-line irinotecan. After progression on infusional 5-fu/fa/irinotecan (folfiri), folfox is the preferred therapy. Evidence from a single randomized trial suggests that additional benefits can be expected with the addition of bevacizumab to the folfox regimen in second-line treatment.
These recommendations apply to adult patients with advanced colorectal cancer who have high performance status (Eastern Cooperative Oncology Group score 0-2). Refer to Appendix A for available treatment options and to Appendix b for recommended dosages and schedules. The folfox regimen is an important component of therapy for advanced colorectal cancer. FIRST-LINE THERAPY: In one trial, folfox was shown to be superior to ifl. The folfox regimen has superior rates of median survival and tumour response. Compared with ifl, folfox has lower incidences of severe nausea, vomiting, diarrhea, and febrile neutropenia, but a higher incidence of peripheral neuropathy. Short-term infusional 5-fu/fa in combination with either oxaliplatin (folfox) or irinotecan (folfiri) are both acceptable alternatives for fit patients when combination therapy is the preferred treatment. Choice of first-line therapy may rely on patient factors and preferences-for example, less neuropathy with irinotecan versus less alopecia with oxaliplatin. SECOND-LINE THERAPY: After progression on first-line anti-thymidylate synthase monotherapy (for example, 5-fu/fa, capecitabine), irinotecan is standard second-line therapy. The folfox regimen is a reasonable alternative for patients with contraindications to the use of second-line irinotecan. After progression on both irinotecan and an anti-thymidylate synthase agent, folfox is the preferred therapy. Recent trials suggest that, as compared with folfox alone, folfox combined with bevacizumab provides additional survival benefits.
The role of radiation therapy, either alone or in combination with chemotherapy, for locally advanced unresectable colorectal cancer is not addressed in this guideline. Use of chronomodulated regimens is a topic that intersects with the use of oxaliplatin/5-fu combinations, particularly chronomodulation of 5-fu in these combinations. Chronomodulation of oxaliplatin has not been extensively studied, and the topic of chronomodulation is beyond the scope of this guideline and is not addressed. Although data exist to support the use of bevacizumab in combination with folfox in second-line treatment, no first-line treatment data are available on which to make a recommendation.
奥沙利铂联合 5-氟尿嘧啶（5-FU）和亚叶酸（FA）在晚期（不可切除的局部晚期或转移性）结直肠癌的一线和二线治疗中的作用是什么？
安大略省癌症护理计划循证护理（PEBC）胃肠道癌症疾病部位小组（GI DSG）的两名成员以及一名方法学家选择和审查了证据。由此产生的实践指南报告已经经过 GI DSG 的审查和批准，该小组由医学和放射肿瘤学家、外科医生、病理学家和患者代表组成。通过邮寄调查获得了安大略省从业者的外部审查。原始指南报告的最终批准由实践指南协调委员会获得。
感兴趣的结果是 1 年生存率、反应率和生活质量。
系统检索了 Medline、Cancerlit、Embase、Guidelines International Network 和 Cochrane 图书馆数据库，以查找相关研究。根据审查的证据提出了建议。通过一项调查，安大略省临床医生对这些建议进行了评估；然后由 GI DSG 对建议进行了修订。该系统评价和修改后的建议得到了 PEBC 内部审查机构的批准。
文献综述发现了 21 项随机对照试验和两项荟萃分析。关于一线治疗的文献发现，与氟尿嘧啶/亚叶酸/伊立替康（IFL）相比，奥沙利铂联合氟尿嘧啶/亚叶酸（FOLFOX）输注在中位生存期和肿瘤反应率方面具有优势，除周围神经病变外，大多数不良反应的发生率较低。对于氟嘧啶单药治疗后的二线治疗，FOLFOX 是二线伊立替康治疗禁忌患者的合理选择。在 IFOLFIRI 进展后，FOLFOX 是首选治疗方法。一项随机试验的证据表明，在二线治疗中添加贝伐单抗可进一步提高 FOLFOX 方案的疗效。
这些建议适用于患有晚期结直肠癌且体能状态良好（东部合作肿瘤学组评分 0-2）的成年患者。可参考附录 A 了解可用的治疗方案，参考附录 B 了解推荐的剂量和方案。FOLFOX 方案是治疗晚期结直肠癌的重要组成部分。一线治疗：一项试验表明，FOLFOX 优于 IFL。FOLFOX 方案具有更高的中位生存期和肿瘤反应率。与 IFL 相比，FOLFOX 发生严重恶心、呕吐、腹泻和发热性中性粒细胞减少症的发生率较低，但周围神经病变的发生率较高。短期输注氟尿嘧啶/亚叶酸联合奥沙利铂（FOLFOX）或伊立替康（FOLFIRI）均为适合联合治疗的患者的可接受替代方案。一线治疗选择可能取决于患者因素和偏好，例如伊立替康的神经病变较轻，奥沙利铂的脱发较轻。二线治疗：在一线抗胸苷酸合成酶单药治疗（例如，5-FU/FA、卡培他滨）进展后，伊立替康是标准的二线治疗。对于不能使用二线伊立替康的患者，FOLFOX 方案是合理的选择。在伊立替康和抗胸苷酸合成酶药物均进展后，FOLFOX 是首选治疗方法。最近的试验表明，与单独使用 FOLFOX 相比，FOLFOX 联合贝伐单抗可提供额外的生存获益。
本指南未涉及局部晚期不可切除结直肠癌的放射治疗（单独或联合化疗）的作用。奥沙利铂/5-FU 联合用药中，尤其是这些联合用药中 5-FU 的时间调节，涉及时间调节方案的作用，特别是 5-FU 的时间调节。奥沙利铂的时间调节尚未得到广泛研究，时间调节的主题超出了本指南的范围，因此未予讨论。虽然有数据支持贝伐单抗联合 FOLFOX 二线治疗，但尚无一线治疗数据可供推荐。
