Fluorouracil-based neoadjuvant chemoradiotherapy with or without oxaliplatin for treatment of locally advanced rectal cancer: An updated systematic review and meta-analysis

Yong-Jing Yang,Zhi-Wen Li,Dan Yue,Zhi-Rui Zhou,Ling Zhao,Shi-Xin Liu,Jin-Lei Yang,Hong-Fen Wu,Ling Cao

doi:10.18632/oncotarget.9995

Abstract

To measure the safety and efficacy of oxaliplatin (OX) application in neoadjuvant chemoradiotherapy (CRT) for locally advanced rectal cancer (LARC), EMBASE, PubMed, Cochrane Library, and Web of Science were used for a literature search. Cochrane's risk of bias tool of randomized controlled trials (RCTs) was used for quality evaluation. The statistical analyses were performed using RevMan 5.3. In addition, 95% confidence intervals (CIs) and pooled risk ratios (RRs) were calculated. Seven RCTs were included in our meta-analysis. After adding OX to fluoropyrimidine (FU), a marginal significant improvement in disease-free survival was noted compared with FU alone (RR = 0.89, 95% CI: 0.78–1.00; P = 0.05). Neoadjuvant CRT with OX significantly decreased the distant metastasis rate (RR = 0.79, 95% CI: 0.67–0.94, P = 0.007). However, no improvement in the local recurrence rate (RR = 0.86, 95% CI: 0.68–1.08; P = 0.19) was noted. In addition, neoadjuvant CRT with OX also significantly increased the pathologic complete response (RR = 1.24, 95% CI: 1.02–1.51; P = 0.03). Grade 3–4 acute toxicity and grade 3–4 diarrhea was considerably higher for OX/FU compared with FU alone. In conclusion, the use of OX on the basis of FU/capecitabine in preoperative CRT is feasible. LARC patients are likely to benefit from CRT regimens with OX.

Highlights

Colorectal cancer ranks as the third highest malignant tumor and the third leading cause of cancer death in the United States [1]
Our metaanalysis revealed that the OX/FU significantly increased the pathologic complete response (pCR) rate compared with the FU only arms (RR =1.24, 95% confidence intervals (CIs): 1.02–1.51; P = 0.03) (Figure 4A)
The results of our meta-analysis indicated marginal significant differences in disease-free survival (DFS) between the group of FU/ capecitabine-based preoperative chemoradiotherapy and the group that employed oxaliplatin (RR =0.89, 95% CI: 0.78– 1.00; P = 0.05)

Summary

Introduction

Colorectal cancer ranks as the third highest malignant tumor and the third leading cause of cancer death in the United States [1]. In 2014, 71,830 men and 65,000 women were estimated to be diagnosed with colorectal cancer, and 26,270 men and 24,040 women died of locally advanced rectal cancer (LARC) [1]. This disease is a major threat to people’s health [2]. The safety and efficacy of OX in neoadjuvant chemoradiotherapy for LARC has been studied in a number of phase II and III clinical trials [12,13,14,15,16,17,18,19,20,21,22] In these studies, high pathologic complete response (pCR) rates www.impactjournals.com/oncotarget were obtained (some trials even reached up to 28%). The maximum tolerated weekly dose of OX plus FU/capecitabine was 60 or 50 mg/m2 [12, 14,15,16,17,18,19,20, 23]

Methods

Results

Conclusion