VEGF inhibitors for the treatment of colorectal cancer : A systematic review of clinical trials

Colorectal cancer (CRC) has been reported to be the second leading cause of cancer-related deaths and the third most common cancer globally. Recent studies have been conducted to develop targeted therapies to improve the treatment of CRC. While chemotherapy drugs were considered the standard treatment, vascular endothelial growth factor (VEGF) inhibitors, acts by suppressing cytokine release and weakening angiogenesis to impair tumor growth. We undertook a systematic review to investigate the impact and efficacy of VEGF inhibitors in treating CRC. Method: According to the Cochrane Handbook’s standard methodology, this study was performed and was reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) ۲۰۲۰ statement. A literature search was conducted across PubMed/Medline, Web of Science, and Scopus databases by combining terms related to CRC and anti-VEGF therapy, including specific drugs in this category. Two independent team members completed screening and data extraction for this study while the third member resolved the conflicts between the two members by careful consideration. We didn’t exclude studies based on follow-up time. Risk of bias assessment was performed by the Cochrane risk of bias tool (The Cochrane Collaboration, Copenhagen, Denmark). Result: After searching, ۶۳۸۴ articles were identified for further examination. Following the removal of duplicates, ۳۶۶۳ studies were screened, and finally, ۳۸ clinical trials studies were included with a population of ۱۸,۷۹۴ patients. The mean age of the participating patients was ۵۵.۶۳ years. VEGF inhibitors demonstrated significant improvements in progression-free survival (PFS) and Overall survival (OS) in randomized-controlled trials (RCT) studies with benefits ranging from ۰.۵ to ۴ and ۰.۲ to ۴ respectively. Comparative analyses showed that using VEGF inhibitor results in reducing mortality and increasing the response rate. Eight eligible RCT studies investigated the treatment effect of VEGF inhibitor in combination with chemotherapy regimens in comparison to the placebo, ۱۶ studies compared various chemotherapy regimens while ۱۴ studies demonstrated their effectiveness without including a control group. Bevacizumab showed a complete response in ۱۹ studies and a partial response in ۳ studies, with an improvement of PFS and OS in several studies in comparison to chemotherapy regimens such as FOLFOX, XELOX, FOLFIRI, CAPOX and fluoropyrimidines. Other drugs in this category, such as cabozantinib, aflibercept, apatinib, and regorafenib, also revealed positive effects on the two common endpoints, however with lesser evidence. Although patients treated with regorafenib demonstrated more adverse effects than other VEGF inhibitors but represented with a better OS versus the placebo group. Cabozantinib yielded only one partial response and wasn’t effective in patients who were treated before with chemotherapy drugs, necessitating further research. While the combination of aflibercept and FOLFIRI didn’t show any complete response, involving time course in one of the studies has demonstrated improvement in PFS and OS versus the placebo group. The addition of VEGF inhibitors doesn’t raise any concern about the safety. Conclusion: The creativity of the combination of VEGF inhibitors with several chemotherapy regimens has shown a great transformation in treating CRC by improving outcomes for patients, and side effects are transient and appear early in the treatment.

کلیدواژه ها:

VEGF inhibitors ، Colorectal cancer ، Bevacizumab