Abstract
There has been debate as to whether targeted agents have beneficial effect when added to adjuvant chemotherapy for patient with colon cancer. We conducted this meta-analysis to investigate the role of targeted agents in the adjuvant treatment of colon cancer. We searched PubMed, MEDLINE, EMBASE, and the Cochrane Library databases. We included phase III trials with the data of disease-free survival (DFS) and adverse events (AEs) of adjuvant treatment with targeted agents. From 5 eligible studies, a total of 9,991 patients with resected colon cancer were included in the meta-analysis of hazard ratio (HR) for 3-year DFS and odds ratio (OR) for grade 3 or higher AEs. The addition of targeted agents showed no improvement of 3-year DFS, compared to standard adjuvant chemotherapy alone (HR = 1.04 [95% confidence interval (CI), 0.96–1.13], P = 0.31). In the subgroup analysis according to the type of targeted agents, neither bevacizumab (HR = 1.03 [95% CI, 0.88–1.21], P = 0.72) nor cetuximab (HR = 1.11 [95% CI, 0.94–1.31], P = 0.22) was associated with improvement of DFS. Moreover, targeted agents significantly increased grade 3 or higher AEs (OR = 1.73 [95% CI, 1.21–2.46], P = 0.003) and treatment-related death (OR = 2.15 [95% CI, 1.16–3.99], P = 0.02). In conclusion, this meta-analysis demonstrates that the addition of targeted agents to standard adjuvant chemotherapy results in no improvement of DFS with increased severe AEs and treatment-related death in patients with resected colon cancer.
Highlights
Colon cancer is the third most common cancer worldwide, accounting for more than 1,300,000 new cases annually and its incidence has sharply increased over the past two decades [1, 2]
In the subgroup analysis according to the type of targeted agents, neither bevacizumab (HR = 1.03 [95% CI, 0.88–1.21], P = 0.72) nor cetuximab (HR = 1.11 [95% CI, 0.94–1.31], P = 0.22) was associated with improvement of disease-free survival (DFS)
We performed this study to investigate the role of targeted agents in patients with resected colon cancer
Summary
Colon cancer is the third most common cancer worldwide, accounting for more than 1,300,000 new cases annually and its incidence has sharply increased over the past two decades [1, 2]. The role of adjuvant chemotherapy to reduce the risk of recurrence after resection has been well established in patients with high-risk stage II or stage III colon cancer [5,6,7,8,9,10]. Until 2004, adjuvant chemotherapy with 5-fluorouracil and leucovorin (5-FU/LV) was the standard regimen for stage III colon cancer, based on the 24% relative reduction of mortality compared with surgery alone [5, 6]. Since the Multicenter International Study of Oxaliplatin/5Fluorouracil/Leucovorin in the Adjuvant Treatment of Colon Cancer (MOSAIC) in 2004 [7], the addition of oxaliplatin to fluorouracil-based adjuvant chemotherapy has been considered the standard treatment for high-risk www.impactjournals.com/oncotarget stage II and stage III colon cancer[8]. Capecitabine, an oral fluoropyrimidine, can be an effective alternative to 5-FU/LV as adjuvant treatment [9, 10]
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