Figueredo A, Germond C, Maroun J, Browman G, Walker-Dilks C, Wong S
Hamilton Regional Cancer Centre, Ont.
Cancer Prev Control. 1997 Dec;1(5):379-92.
Should patients with resected stage II colon cancer receive adjuvant therapy?
To make recommendations regarding the use of adjuvant therapy in the treatment of resected stage II colon cancer.
Overall survival is the primary outcome of interest. Secondary outcomes are disease-free survival and adverse effects of the treatment regimens.
PERSPECTIVE (VALUES): Evidence was selected and reviewed by 2 members of the Provincial Gastrointestinal Disease Site Group (GI DSG) of the Cancer Care Ontario Practice Guidelines Initiative. The recommendations resulting from this review have been approved by the GI DSG, which comprise medical and radiation oncologists, surgeons and epidemiologists. Community representatives did not participate in the development of this practice guideline but will do so in future guidelines development.
There are 25 published randomized controlled trials (RCTs) and 1 meta-analysis. The GI DSG pooled data from 11 of the 25 RCTs that provided adequate data.
The 25 RCTs are grouped according to the type of therapy and whether the control patients received no treatment (observation) or other adjuvant therapy after resection. Because the trials usually included patients with stage II and III cancer, the complete trial results and those for a subset of patients with stage II disease were analysed. Although the overall trial results showed a survival benefit for adjuvant treatments, the benefit was not significant for stage II patients. A meta-analysis of 11 trials comparing adjuvant treatment with observation in patients with stage II cancer indicated no significant reduction in the odds ratio (OR) for death (OR 0.83; 95% confidence interval [CI] 0.62 to 1.10). The OR for death among patients receiving chemotherapy by portal vein infusion (PVI) was 0.62 (95% CI 0.35 to 1.11).
The toxic effects of 5-fluorouracil (5-FU) with either levamisole or leucovorin, or both, were mild to moderate and consisted mostly of stomatitis, diarrhea and myelosuppression; 5% of patients required hospital admission. 5-FU plus levamisole was associated with transient neurotoxic effects in 18% of patients. Toxic effects associated with PVI were mild, rare and mostly consisted of leukopenia and diarrhea; 1% of patients experienced bowel perforation.
Adjuvant therapy is not recommended at this time for the routine management of patients with resected stage II colon cancer. Patients with stage II disease and high-risk factors (bowel obstruction, tumour adhesion, invasion, perforation or aneuploidy) have a poorer prognosis, similar to that of patients with stage III colon cancer. For individual management, these patients should be made aware of their prognosis; treatment can be considered after the uncertainty of the value of adjuvant therapy has been explained to the patient. The enrolment of patients with high-risk stage II disease in clinical trials is encouraged. Trials comparing adjuvant therapy with observation are needed and are ethically acceptable in stage II colon cancer.
接受过手术的II期结肠癌患者是否应接受辅助治疗？
就是否在接受过手术的II期结肠癌治疗中使用辅助治疗提出建议。
总生存期是主要关注的结果。次要结果为无病生存期和治疗方案的不良反应。
观点（价值观）：安大略癌症护理实践指南倡议组织的省级胃肠疾病领域小组（GI DSG）的两名成员挑选并审查了证据。该审查得出的建议已获GI DSG批准，该小组由医学肿瘤学家、放射肿瘤学家、外科医生和流行病学家组成。社区代表未参与本实践指南的制定，但未来指南制定时将会参与。
有25项已发表的随机对照试验（RCT）和1项荟萃分析。GI DSG汇总了25项RCT中11项提供了充分数据的试验的数据。
25项RCT根据治疗类型以及对照患者在切除术后是否未接受治疗（观察）或接受其他辅助治疗进行分组。由于试验通常纳入II期和III期癌症患者，因此分析了完整的试验结果以及II期疾病患者亚组的结果。尽管总体试验结果显示辅助治疗有生存益处，但对II期患者而言该益处并不显著。一项对11项比较II期癌症患者辅助治疗与观察的试验的荟萃分析表明，死亡比值比（OR）无显著降低（OR 0.83；95%置信区间[CI]0.62至1.10）。接受门静脉输注（PVI）化疗的患者的死亡OR为0.62（95%CI 0.35至1.11）。
5-氟尿嘧啶（5-FU）联合左旋咪唑或亚叶酸，或两者联合使用的毒性作用为轻至中度，主要包括口腔炎、腹泻和骨髓抑制；5%的患者需要住院治疗。5-FU加左旋咪唑使18%的患者出现短暂性神经毒性作用。与PVI相关的毒性作用较轻，较为罕见，主要包括白细胞减少和腹泻；1%的患者发生肠穿孔。
目前不建议对接受过手术的II期结肠癌患者进行常规辅助治疗。伴有高危因素（肠梗阻、肿瘤粘连、侵犯、穿孔或非整倍体）的II期疾病患者预后较差，与III期结肠癌患者相似。对于个体化治疗，应让这些患者了解其预后；在向患者解释辅助治疗价值的不确定性后可考虑进行治疗。鼓励将高危II期疾病患者纳入临床试验。需要开展比较辅助治疗与观察的试验，且在II期结肠癌中从伦理角度是可接受的。
