Oral drugs in the treatment of metastatic colorectal cancer

Abstract

Colorectal cancer (CRC) is one of the most common forms of cancer, with an estimated 1.36 million new cases and almost 700,000 deaths annually. Approximately 21% of patients with CRC have metastatic disease at diagnosis. The objective of this article is to review the literature on the efficacy and safety of oral drugs available for the treatment of metastatic colorectal cancer (mCRC). Several such drugs have been developed, and fluoropyrimidines are the backbone of chemotherapy in this indication. They exert their antitumour activity by disrupting the synthesis and function of DNA and RNA. Oral fluoropyrimidines include prodrugs capecitabine, tegafur, eniluracil/5-fluorouracil, tegafur/uracil, tegafur/gimeracil/oteracil and trifluridine/tipiracil (FTD/TPI). Oral drugs offer several advantages over injectable formulations, including convenience, flexibility, avoidance of injection-related adverse events (AEs) and, in some circumstances, lower costs. However, oral drugs may not be suitable for patients with gastrointestinal obstruction or malabsorption, they may result in reduced treatment adherence and should not be co-administered with drugs that interfere with absorption or hepatic metabolism. Oral fluoropyrimidines such as capecitabine, as monotherapy or in combination with oxaliplatin, irinotecan or bevacizumab, are as effective as intravenous 5-fluorouracil (5-FU) in first-line treatment of mCRC. Other oral fluoropyrimidines, such as FTD/TPI, are effective in patients with mCRC who are refractory, intolerant or ineligible for 5-FU. In addition, oral fluoropyrimidines are used in adjuvant treatment of mCRC. Regorafenib is an oral multikinase inhibitor used in patients in whom several previous lines of therapy have failed. Frequent AEs associated with oral drugs used in the treatment of CRC include hand-foot syndrome and gastrointestinal and haematological toxicities.

Effective Delivery of siRNA-Loaded Nanoparticles for Overcoming Oxaliplatin Resistance in Colorectal Cancer

“…The early-stage CRC patients may benefit from radical surgical resection with a higher disease-free survival (DFS) rate of nearly 90% ( 2 , 3 ). However, the advanced or metastatic CRC patients might not have the chance to accept the radical surgical resection ( 3 , 4 ). As a result, chemotherapy, targeted therapy, or immunotherapy might be a better preferable therapeutic method for those patients.…”

Classification of colon adenocarcinoma based on immunological characterizations: Implications for prognosis and immunotherapy

“…The 12 prognostic hub genes are the major immune genes related to the disease progression risk of IS1 and IS2-COAD, which may serve as potential prognostic and therapeutic markers. Among them, PDGFRB -related multitargeted receptor tyrosine kinase inhibitor regorafenib (BAY 73-4506) has been FDA approved for the treatment of metastatic COAD that has progressed after all standard therapies ( 62 ). PDGFRB + cancer-associated fibroblasts (CAFs) are an important component of stromal cells in the tumor microenvironment.…”

Therapeutic Potential of Naturally Occurring Small Molecules to Target the Wnt/β-Catenin Signaling Pathway in Colorectal Cancer

“…Treatment of CRC depends on the staging and may include laparoscopic removal of polyps or surgical removal of damaged areas of the intestine [ 83 , 84 , 85 , 86 ]. 5-Fluorouracil (5-FU)-based monotherapy is generally the first-line systemic approach used to treat frail or elderly patients [ 87 , 88 , 89 ]. On the other hand, in reasonably healthy patients, first-line therapy consists of combined regimens of 5-FU and oxaliplatin (FOLFOX or CAPOX) or regimens based on irinotecan (FOLFIRI or CAPIRI).…”