Capecitabine (Xeloda)

General information

Class/mechanism: Pyrimidine analog, antimetabolite, inhibitor of thymidylate synthase. Converted in vivo to fluorouracil (5-FU), which is metabolized to 5-fluoro-2'-deoxyuridine monophosphate (FdUMP) and 5-fluorouridine triphosphate (FUTP). FdUMP inhibits DNA synthesis by binding to thymidylate synthase and inhibiting production of thymidylate; FUTP interferes with RNA processing when it is mistakenly incorporated in place of uridine triphosphate (UTP).
Route: PO
Extravasation: n/a

For conciseness and simplicity, HemOnc.org currently will focus on treatment regimens and not list information such as: renal/hepatic dose adjustments, metabolism (including CYP450), excretion, monitoring parameters (although this will be considered for checklists), or manufacturer. Instead, for the most current information, please refer to your preferred pharmacopeias such as Micromedex, Lexicomp, Medscape, UpToDate (courtesy of Lexicomp), or the prescribing information.

Patient safety

DPYD intermediate or poor metabolizers: Results in higher adverse reaction risk (severe, life-threatening, or fatal toxicities). No dosage has proven safe in poor metabolizers, and insufficient data are available to recommend a dosage in intermediate metabolizers. Withhold or discontinue in the presence of early-onset or unusually severe toxicity.

EMA has recommended that patients should be tested for the lack of the enzyme dihydropyrimidine dehydrogenase (DPD) before starting cancer treatment with fluorouracil given by injection or infusion (drip) or with the related medicines, capecitabine and tegafur.

Diseases for which it is used

• Anal cancer
• Breast cancer
• Cholangiocarcinoma
• Colorectal cancer
  • Colon cancer
  • Rectal cancer
• Esophageal cancer
  • Esophageal adenocarcinoma
  • Esophageal squamous cell carcinoma
• Gallbladder cancer
• Gastric cancer
• Hepatocellular carcinoma
• Nasopharyngeal carcinoma
• Pancreatic cancer
• Pancreatic NET
• Thymoma

Patient drug information

• Capecitabine (Xeloda) package insert
• Capecitabine (Xeloda) patient drug information (Chemocare)
• Capecitabine (Xeloda) patient drug information (UpToDate)

History of changes in FDA indication

Breast cancer

• 1998-04-30: Initial accelerated approval for the treatment of patients with metastatic breast cancer resistant to both paclitaxel and an anthracycline-containing chemotherapy regimen or resistant to paclitaxel and for whom further anthracycline therapy is not indicated, eg, patients who have received cumulative doses of 400 mg/m² of doxorubicin or doxorubicin equivalents. Resistance is defined as progressive disease while on treatment, with or without an initial response, or relapse within 6 months of completing treatment with an anthracycline-containing adjuvant regimen. (Based on SO14697)
  • 2001-09-07: Converted to regular approval in combination with docetaxel is indicated for the treatment of patients with metastatic breast cancer after failure of prior anthracycline containing chemotherapy. (Based on SO14999)
• 2022-12-14: Project Renewal revision for treatment of patients with advanced or metastatic breast cancer as a single agent if an anthracycline- or taxane-containing chemotherapy is not indicated. (Based on SO14697)
• 2022-12-14: Project Renewal revision for treatment of patients with advanced or metastatic breast cancer in combination with docetaxel after disease progression on prior anthracycline-containing chemotherapy. (Based on SO14999)

Colon cancer

• 2005-06-15: New indication as a single agent for adjuvant treatment in patients with Dukes’ C colon cancer who have undergone complete resection of the primary tumor when treatment with fluoropyrimidine therapy alone is preferred. (Based on X-ACT)
• 2022-12-14: Project Renewal revision as adjuvant treatment of patients with Stage III colon cancer as a single agent. (Based on X-ACT)
• 2022-12-14: Project Renewal new indication as adjuvant treatment of patients with Stage III colon cancer as a component of a combination chemotherapy regimen. (Based on XELOXA)

Colorectal cancer

• 2001-04-30: New indication as first-line treatment of patients with metastatic colorectal carcinoma when treatment with fluoropyrimidine therapy alone is preferred. (Based on SO14695 & SO14796)
• 2022-12-14: Project Renewal revision as treatment of patients with unresectable or metastatic colorectal cancer as a single agent. (Based on SO14695 & SO14796)
• 2022-12-14: Project Renewal new indication as treatment of patients with unresectable or metastatic colorectal cancer as a component of a combination chemotherapy regimen. (Based on NO16966)

Gastric cancer, Esophageal cancer, and Gastroesophageal junction cancer

• 2022-12-14: Project Renewal new indication for treatment of adults with unresectable or metastatic gastric, esophageal, or gastroesophageal junction cancer as a component of a combination chemotherapy regimen. (Based on REAL-2)
• 2022-12-14: Project Renewal new indication for treatment of adults with HER2-overexpressing metastatic gastric or gastroesophageal junction adenocarcinoma who have not received prior treatment for metastatic disease as a component of a combination regimen. (Based on ToGA)

Pancreatic cancer

• 2022-12-14: Project Renewal new indication for adjuvant treatment of adults with pancreatic adenocarcinoma as a component of a combination chemotherapy regimen. (Based on ESPAC-4)

Rectal cancer

• 2022-12-14: Project Renewal new indication as perioperative treatment of adults with locally advanced rectal cancer as a component of chemoradiotherapy. (Based on Rektum-III)

History of changes in EMA indication

• 1998-04-30: EURD
• 2001-02-02: Initial market authorization as Xeloda.

History of changes in Health Canada indication

• 1998-08-31: Initial notice of compliance
• 2000-07-17: Indicated as monotherapy for the first-line treatment of patients with metastatic colorectal cancer.
• 2001-12-28: New indication in combination with docetaxel for the treatment of patients with advanced or metastatic breast cancer after failure of prior anthracycline containing chemotherapy.
• 2005-12-07: Indicated with conditions as monotherapy for the adjuvant treatment of patients with stage III (Dukes’ stage C) colon cancer.
  • 2008-10-23: Conditions were met as monotherapy for the adjuvant treatment of patients with stage III (Dukes’ stage C) colon cancer.
• 2009-12-03: In combination with oxaliplatin is indicated for the treatment of metastatic colorectal cancer following failure of irinotecan-containing combination chemotherapy.
• Uncertain date: Indicated as monotherapy for the treatment of advanced or metastatic breast cancer after failure of standard therapy including a taxane, unless therapy with a taxane is clinically contraindicated.
• Uncertain date: Indicated in combination with docetaxel for the treatment of patients with advanced or metastatic breast cancer after failure of prior anthracycline containing chemotherapy.

History of changes in PMDA indication

• 2007-12-12: New indication and dosage for use as a postoperative adjuvant chemotherapy of colon cancer.
• 2009-09-18: New additional indication for combination therapy with other anticancer drugs (XELOX + BV regimen) for advanced or recurrent colorectal cancer not suited for curative resection.
• 2011-02-23: New additional indication and a new dosage for the treatment of unresectable advanced or recurrent gastric cancer.
• 2015-11-20: Revised indication for the treatment of gastric cancer.
• 2016-08-26: New additional indication and a new dosage for adjuvant chemotherapy for rectal cancer.

Also known as

• Code name: Ro 09-1978/000
• Generic names: capecitabine RDT, kapesitabin
• Brand names: Cabita, Capebin, Capegard, Capnat, Caposib, Capsy, Caxeta, Citabin, Ecansya, Flagoda, Naprocap, Skemca, Xeloda, Xlotabin