capecitabine
capecitabine
Overview
Capecitabine is an orally administered prodrug of 5-fluorouracil (5-FU), a fluoropyrimidine antimetabolite widely used in oncology. Following absorption, capecitabine undergoes a sequential three-step enzymatic conversion — first in the liver and then preferentially within tumor tissue — culminating in the release of active 5-FU. This tumor-preferential activation is mediated by thymidine phosphorylase, which is overexpressed in many malignancies, thereby concentrating cytotoxic activity at the tumor site while sparing normal tissue. Once converted to 5-FU, the drug inhibits thymidylate synthase, disrupting DNA synthesis and inducing cell death in rapidly proliferating cancer cells. Capecitabine is approved for the treatment of multiple solid tumors, including colorectal cancer, gastric cancer, and breast cancer, and is frequently combined with platinum-based agents, Targeted therapies, and immune checkpoint inhibitors to enhance efficacy.
As a cornerstone of combination regimens, capecitabine offers the practical advantage of oral administration over intravenous 5-FU infusion, improving patient convenience and quality of life. Its combination with oxaliplatin — commonly designated CAPOX or XELOX — is a standard-of-care backbone in gastric, gastro-oesophageal junction (GEJ), and colorectal cancers. The drug is also employed in maintenance and frailty-adapted dosing strategies, reflecting its versatility across diverse patient populations and disease stages.
Focus of Latest Publications
Recent publications on capecitabine have focused largely on its role in gastrointestinal and breast cancer treatment, both as a standalone comparator and as part of combination regimens. In hormone receptor-positive, HER2-negative metastatic breast cancer, the phase 3 FAMILY trial directly compared capecitabine with fulvestrant as maintenance therapy after first-line chemotherapy. Fulvestrant produced longer progression-free survival and fewer grade ≥3 adverse events and treatment discontinuations than capecitabine, suggesting that capecitabine may be less favorable than endocrine maintenance in this setting.
Several studies examined capecitabine-containing combinations in gastric cancer. A phase 3 trial evaluated camrelizumab plus capecitabine and oxaliplatin (CAPOX) with different maintenance strategies as initial treatment for gastric or gastro-oesophageal junction adenocarcinoma. Another study used mass cytometry and paired tissue analyses to investigate immune changes during pembrolizumab plus XELOX, identifying early blood myeloid changes, including increased monocytes in responders, as correlates of clinical response. In frail patients with advanced HER2-positive gastric cancer, a pilot case series assessed alternate-day capecitabine plus trastuzumab to explore feasibility and tolerability, reflecting interest in lower-burden dosing approaches.
Capecitabine also appeared in studies addressing treatment optimization and special populations. A case report described the pharmacokinetic and pharmacogenomic profile of capecitabine plus oxaliplatin in a patient with gastric cancer undergoing hemodialysis, highlighting the challenge of using CapeOX in patients with renal replacement therapy. In metastatic breast cancer, a correspondence on DPYD genotyping before capecitabine administration emphasized the clinical value of pharmacogenomic testing to reduce fluoropyrimidine-related toxicity and discussed implementation considerations such as turnaround time, dose decision support, and toxicity surveillance.
Other publications placed capecitabine within broader combination strategies or supportive care contexts. A randomized trial evaluated [177Lu]Lu-DOTATATE PRRT plus CAPTEM, a regimen that includes capecitabine and temozolomide, in progressive pancreatic and small bowel neuroendocrine tumors. In pancreatic cancer, a phase 2 study investigated nab-paclitaxel plus S-1, while another randomized trial compared liposomal irinotecan plus S-1 with liposomal irinotecan plus 5-fluorouracil. Outside direct efficacy studies, one report examined how side effects influence self-management in patients taking capecitabine, focusing on the role of medication beliefs, and another machine learning study in oral chemotherapy sought to predict unplanned acute care in outpatients receiving S-1. Together, these publications show capecitabine being studied across efficacy, tolerability, pharmacogenomics, dosing feasibility, and patient self-management.