Capecitabine

Capecitabine is an oral drug marketed by Roche as Xeloda. It is used in the treatment of metastatic breast and colorectal cancers. Capecitabine is an antimetabolite, a drug that has a similar chemical structure to a substance normally found in the cell, but interferes with the cell's normal functions. It belongs to a class of chemotherapeutic agents called fluoropyrimidines.

Other Names

• 5'deoxy-5-fluoro-N-cytidine

Uses

The indications for capecitabine (in the United States and Europe) are:

• First line treatment for metastatic colorectal cancer.
• Duke's Stage C colon cancer when the tumor has been completely resected and fluoropyrimidine therapy is desired. Capecitabine is likely to have increased efficacy when combined with other chemotherapeutic agents but can also be prescribed alone.
• Metastatic breast cancer either in combination with docetaxel, and as monotherapy for metastatic breast cancer resistant to paclitaxel and anthracycline therapy (US) or failing intensive chemotherapy (Europe). ^[1]

How Capecitabine Is Taken

Capecitabine is taken in oral tablet form twice a day - morning and night. The medicine is taken with a glass of water within 30 minutes of a meal. The pills are usually given every day for fourteen days, then not taken for seven days. Dosing depends on body size but may need to be adjusted if side effects occur or if blood counts are low.

How it works

Chemical structure of capecitabine. Source:Wikimedia Commons

Capecitabine is not active until it has been enzymatically converted in the tumor to 5-fluorouracil, where it inhibits DNA synthesis and slows growth of tumor tissue. Before it becomes active as 5-fluorouracil, capecitabine must be sequentially converted by three different enzymes. The parent compound is first converted to 5'-deoxy-5-fluorocytidine, then to 5'-deoxy-5-fluorouridine, and finally to 5-fluorouracil. In some patients with colon, rectum or breast cancer, this substance stops cancer cells from growing and decreases the size of the tumor by decreasing the rate of DNA synthesis.

Benefits

Leucovorin-modulated 5-fluorouracil (5-FU) has been used for a number of years in the treatment of colorectal cancer. The development of an oral version of the medication has made the chemotherapy protocol for colorectal cancer, as well as breast cancer, more easily tolerated, easier and more convenient. In addition, oral capecitabine is as effective as IV 5-FU and has demonstrated a better response rate. ^[2]

Side Effects

• Diarrhea
• Nausea
• Vomiting
• Sores in the mouth and throat
• Numbness, tingling, itching of the hands or feet
• hand-and-foot syndrome
• Skin rash, red, irritated or dry skin
• Decreased white blood cell count with increased risk of infection
• Decreased platelet count with increased risk of bleeding
• Decreased red blood cell count with increased risk of tiredness (fatigue)

Less common side effects

• Abdominal pain
• Constipation
• Heartburn
• Fever
• Pins and needles in hands and feet
• Headache
• Dizziness
• Insomnia
• Eye irritation
• Abnormal liver function tests
• Swelling of the ankles

Risks

Interactions

There is an interaction between capecitabine and warfarin which can lead to blood clotting abnormalities and excessive bleeding; deaths have been reported. If capecitabine and warfarin are taken together, close monitoring of the INR or prothrombin time (PT) is essential.

Precautions

Patients with severe renal impairment, who are or may become pregnant, who are breast feeding, or who are allergic to 5-fluorouracil should not take capecitabine. Men should also practice effective birth control while taking the drug.

History

Manufacturer

Roche Laboratories, Inc.

Research

Recent discoveries

A recent clinical trial thorough the National Cancer Institute combined the chemotherapeutic agent lapatinib (Tykerb) with capecitabine to treat advanced Her-2 positive breast cancer thought to be resistant or unresponsive to trastuzumab (Herceptin) . The study was stopped early for ethical reasons (the overwhelming success of the combination treatment). ^[3]

Future research

Capecitabine is also being studied in combination with the chemotherapeutic agents trastuzumab ^[4] , gemcitabine ^[5] , and vinorelbine ^[6]

Clincal Trials

Capecitabine Trials

National Cancer Institute: Capecitabine (Xeloda ®) an Alternative in Post-Surgery Treatment of Stage III Colon Cancer

ClincalTrials.gov: Xena Study

References

1. ↑ Wagstaff AJ, Ibbotson T, Goa KL. Capecitabine: a review of its pharmacology and therapeutic efficacy in the management of advanced breast cancer. Drugs. 2003;63(2):217-36. Abstract
2. ↑ Cunningham D, Coleman R. New options for outpatient chemotherapy--the role of oral fluoropyrimidines. Cancer Treat Rev. 2001 Aug;27(4):211-20. Abstract
3. ↑ Geyer CE, Forster J, Lindquist D, Chan S, Romieu CG, Pienkowski T. Lapatinib plus capecitabine for HER2-positive advanced breast cancer. N Engl J Med. 2006 Dec 28;355(26):2733-43. Abstract | Full Text
4. ↑ Schaller G, Fuchs I, Gonsch T, et al. Phase II study of capecitabine plus trastuzumab in human epidermal growth factor receptor 2 overexpressing metastatic breast cancer pretreated with anthracyclines or taxanes. J Clin Oncol. 2007 Aug 1;25(22):3246-50. Epub 2007 Jun 18. Abstract
5. ↑ Benekli M, Yildiz R, Uner A, Er O, Yamac D, Alkis N. Gemcitabine plus capecitabine combination in metastatic breast cancer patients previously treated with anthracyclines and taxanes. Oncology. 2007;72(5-6):308-13. Epub 2008 Jan 14. Abstract
6. ↑ Ahn JH, Kim SB, Kim TW, et al. Capecitabine and vinorelbine in patients with metastatic breast cancer previously treated with anthracycline and taxane. J Korean Med Sci. 2004 Aug;19(4):547-53. Abstract

External Links

FDA Xeloda Information page

National Cancer Institute:

• FDA Approval for Capecitabine
• Colon and Rectal Cancer
• Breast Cancer