You are using an outdated browser. We suggest you update your browser for a better experience. Click here for update.
Close this notification.
Skip to main content Skip to search

COVID-19: Obtenez les dernières mises à jour ou faites une autoévaluation.

Les traitements par chimiothérapie et autres traitements systémiques pourraient être modifiés en raison de la COVID-19. Vous trouverez de plus amples renseignements à la page Traitements systémiques pendant la pandémie de la COVID-19.

Certaines de ces informations ou toutes, dans certains cas, n’apparaissent qu’en Anglais. Vous pouvez demander la version française

A - Regimen Name

CAPE Regimen
Capecitabine


Disease Site
Unknown Primary

Intent
Palliative

Regimen Category
Evidence-Informed :

Regimen is considered appropriate as part of the standard care of patients; meaningfully improves outcomes (survival, quality of life), tolerability or costs compared to alternatives (recommended by the Disease Site Team and national consensus body e.g. pan-Canadian Oncology Drug Review, pCODR).  Recommendation is based on an appropriately conducted phase III clinical trial relevant to the Canadian context OR (where phase III trials are not feasible) an appropriately sized phase II trial. Regimens where one or more drugs are not approved by Health Canada for any indication will be identified under Rationale and Use.


Supplementary Public Funding

capecitabine
ODB - General Benefit (capecitabine) (ODB Formulary )

 
B - Drug Regimen

capecitabine
1000-1250 mg /m² PO BID* Days 1 to 14

(*Total dose 2000-2500 mg/m2/day, available in 150 mg and 500 mg tablets)

back to top
 
C - Cycle Frequency

REPEAT EVERY 21 DAYS

Until disease progression or unacceptable toxicity

 
D - Premedication and Supportive Measures

Antiemetic Regimen:

Low – No routine prophylaxis; PRN recommended


Febrile Neutropenia Risk:

Low

Other Supportive Care:

  • Topical emollients (e.g. hand creams, udder balm) may ameliorate the manifestations of hand-foot syndrome in patients receiving capecitabine.

  • Standard antidiarrheal agents (e.g. loperamide) should be initiated, as medically appropriate, as early as possible.

Also refer to CCO Antiemetic Recommendations.

 
E - Dose Modifications

Doses should be modified according to the protocol by which the patient is being treated. 

Use capecitabine with extreme caution in patients with partial DPD deficiency; reduce the initial dose substantially, monitor frequently and adjust the dose for toxicity as recommended in the dosage with toxicity section. In patients with unrecognized DPD deficiency, acute, life-threatening toxicity may occur; discontinue if acute grade 2-4 toxicity develops.

 

Dosage with toxicity

Patients with baseline neutrophil counts of <1.5 x 109/L and/or thrombocyte counts of <100 x 109/L should not receive capecitabine therapy.

Patients should be informed of the need to interrupt treatment immediately if moderate or severe toxicity occurs. Supportive care should be provided, including loperamide for diarrhea. 

Doses should not be re-escalated if reduced for toxicity.  Missed or omitted doses of capecitabine should not be replaced.

Dose modifications are mandatory for gastrointestinal, dermatological toxicity, neurotoxicity and hyperbilirubinemia.  Practitioner may elect not to reduce dose for other toxicities unlikely to become serious or life-threatening.

 

Non-hematologic Toxicity:

 
Toxicity

Action During a Course of Therapy

Dose Adjustment for Next Cycle  

(% of starting dose)

 
Grade 1
 
 
Maintain dose level
 
Maintain dose level
 
Grade 2

1st appearance

2nd appearance

3rd appearance

4th appearance

 
 
 

Hold until resolved to ≤ grade 1

Hold until resolved to ≤ grade 1

Hold until resolved to ≤ grade 1

Discontinue treatment permanently

 
 

100%

75%

50%

Not applicable

 
Grade 3

1st appearance

2nd appearance

3rd appearance, OR any evidence of Stevens-Johnson syndrome or Toxic epidermal necrolysis

 
 

Hold until resolved to ≤ grade 1

Hold until resolved to ≤ grade 1

Discontinue treatment permanently

 
 

75%

50%

Not applicable

 
Grade 4
 
1st appearance, including SJS or TEN, OR cardiotoxicity OR
acute renal failure
 
 
 
 
 
 

 

2nd appearance OR any occurrence of confirmed leukoencephalopathy
 
 
 
Discontinue permanently
                 OR
If physician deems it to be in the patient’s best interest to continue and no evidence of Stevens-Johnson syndrome or toxic epidermal necrolysis, interrupt until resolved to ≤ grade 1.
 
 
 
 

 Discontinue permanently

 
 
 
Discontinue
OR
50%

 

 

 

 

 

Not applicable

 

 

Hematologic Toxicity:

Hold capecitabine during a treatment cycle in the presence of grade 3 or 4 hematologic toxicity.



Hepatic Impairment

Hepatic impairment Capecitabine Dose
Mild to moderate impairment No starting dose adjustment necessary
Severe No data, has not been studied

 


Renal Impairment

Moderate renal impairment results in an increase in severe toxicity.

Creatinine Clearance (mL/min)

% of Starting Dose

51 - 80

100 % with close monitoring

30 - 50

75 % (use with caution)

<30

discontinue 

 


Dosage in the Elderly

No dose adjustment for the starting dose is required but patients should be closely monitored. Older patients (≥ 65 years) are more susceptible to the effects of fluoropyrimidine-based therapies with increased grade 3/4 adverse effects, especially when used in combination.


 
F - Adverse Effects

Refer to capecitabine drug monograph(s) for additional details of adverse effects


Very common (≥ 50%)

Common (25-49%)

Less common (10-24%)

Uncommon (< 10%),

but may be severe or life-threatening

  • Palmar-plantar erythrodysesthesia syndrome (PPES) (may be severe)
  • Diarrhea (may be severe)
  • Nausea, vomiting
  • Mucositis
  • ↑ Bilirubin (may be severe)
  • Fatigue
  • Abdominal pain
  • Cardiotoxicity
  • Arterial / Venous thromboembolism
  • Hypersensitivity
  • Myelosuppression +/- infection, bleeding
  • Leukoencephalopathy
  • GI perforation / obstruction
  • Nephrotoxicity
  • Hepatic failure
  • Idiopathic thrombocytopenic purpura
  • Eye disorders
  • Dehydration
  • Rash
 
G - Interactions

Refer to capecitabine drug monograph(s) for additional details


  • Concomitant use with sorivudine or analogues is contraindicated, given the increased risk of capecitabine toxicity (may be fatal). Wait at least 4 weeks after sorivudine (or chemically related analogues) treatment before starting capecitabine.

  • Avoid concomitant administration with phenytoin as capecitabine may increase phenytoin levels.

  • Caution and monitor with the coadministration of leucovorin as this may increase capecitabine toxicity.

  • Caution and monitor PT/INR when administered with warfarin; capecitabine increases warfarin exposure.

  • Caution with the use of proton pump inhibitors and monitor for reduced effectiveness of capecitabine; consider switching to a magnesium and aluminum hydroxide-containing antacid.

 
H - Drug Administration and Special Precautions

Refer to capecitabine drug monograph(s) for additional details


Administration:

  • Oral self-administration; drug available by outpatient prescription.

  • Doses are given orally approximately 12 hours apart, within 30 minutes after the end of a meal.

  • Swallow tablets whole; do not crush or cut tablets.

  • If a capecitabine dose is missed, skip this and give the next dose at the usual time. Missed or omitted doses should not be replaced.

  • Store tablets at 15ºC to 30ºC in the original package.

 


Contraindications:

  • Patients who have a known hypersensitivity to capecitabine, its excipients, 5-fluorouracil or any ingredient in the formulation or component of the container.

  • Patients with severe renal impairment (CrCl <30 mL/min).

  • Patients with known near or complete absence of DPD (dihydropyrimidine dehydrogenase) activity.

  • Concomitant use with sorivudine or related analogues (i.e. brivudine), given potential fatal drug interaction.

 

 

Other Warnings/Precautions:

  • Contains lactose and should not be used in patients with hereditary galactose/glucose/lactase disorders.
  • Use with caution in patients with risk factors for dehydration, pre-existing renal dysfunction or on nephrotoxic agents.

  • Use with caution in patients with a history of cardiovascular disease as well as patients taking anticoagulants such as warfarin.

  • Patients with partial DPD deficiency - use with extreme caution.

 

 

Pregnancy/Lactation:

  • Capecitabine is not recommended for use in pregnancy.  Adequate contraception should be used by both sexes during treatment, and for at least 6 months after the last dose.

  • Breastfeeding is not recommended.

    • Due to the potential for serious adverse reactions in the breastfed infant, breast-feeding is not recommended during treatment and for 2 weeks after the last dose.

  • Fertility effects: Probable

 
I - Recommended Clinical Monitoring

Treating physicians may decide to monitor more or less frequently for individual patients but should always consider recommendations from the product monograph.

Recommended Clinical Monitoring

  • CBC; Baseline and at each visit

  • Renal function tests; Baseline and as clinically indicated

  • INR and/or PT; Baseline and as clinically indicated if patient is on anticoagulants

  • Clinical toxicity assessment for diarrhea, dehydration, infection, stomatitis, rash or hand-foot syndrome, cardiac, hepatic and neurotoxicity; At each visit

  • Grade toxicity using the current NCI-CTCAE (Common Terminology Criteria for Adverse Events) version

Suggested Clinical Monitoring

  • Liver function tests; Baseline and as clinically indicated (if severe organ failure suspected)

back to top
 
J - Administrative Information

Outpatient prescription for home administration


 
K - References

Capecitabine drug monograph, Cancer Care Ontario.

Van Cutsem E, Twelves C, Cassidy J, et al. Oral capecitabine compared with intravenous fluorouracil plus leucovorin in patients with metastatic colorectal cancer: results of a large phase III study. J Clin Oncol 2001;19(21):4097-106.

Hoff PM, Ansari R, Batist G, et al.  Comparison of oral capecitabine versus intravenous fluorouracil plus leucovorin as first-line treatment in 605 patients with metastatic colorectal cancer: results of a randomized phase III study. J Clin Oncol 2001;19(8):2282-92. 

November 2019 Updated Adverse Effects, Interactions and Drug Administration and Special Precautions sections and emetic risk category.


back to top
 
M - Disclaimer

Regimen Abstracts
A Regimen Abstract is an abbreviated version of a Regimen Monograph and contains only top level information on usage, dosing, schedule, cycle length and special notes (if available). It is intended for healthcare providers and is to be used for informational purposes only. It is not intended to constitute or be a substitute for medical advice, and all uses of the Regimen Abstract are subject to clinical judgment. Such information is provided on an “as-is” basis, without any representation, warranty, or condition, whether express, or implied, statutory or otherwise, as to the information’s quality, accuracy, currency, completeness, or reliability, and Cancer Care Ontario disclaims all liability for the use of this information, and for any claims, actions, demands or suits that arise from such use.
Information in regimen abstracts is accurate to the extent of the ST-QBP regimen master listings, and has not undergone the full review process of a regimen monograph.  Full regimen monographs will be published for each ST-QBP regimen as they are developed.
Regimen Monographs
Refer to the New Drug Funding Program or Ontario Public Drug Programs websites for the most up-to-date public funding information.
The information set out in the drug monographs, regimen monographs, appendices and symptom management information (for health professionals) contained in the Drug Formulary (the "Formulary") is intended for healthcare providers and is to be used for informational purposes only. The information is not intended to cover all possible uses, directions, precautions, drug interactions or adverse effects of a particular drug, nor should it be construed to indicate that use of a particular drug is safe, appropriate or effective for a given condition. The information in the Formulary is not intended to constitute or be a substitute for medical advice and should not be relied upon in any such regard. All uses of the Formulary are subject to clinical judgment and actual prescribing patterns may not follow the information provided in the Formulary.
The format and content of the drug monographs, regimen monographs, appendices and symptom management information contained in the Formulary will change as they are reviewed and revised on a periodic basis. The date of last revision will be visible on each page of the monograph and regimen. Since standards of usage are constantly evolving, it is advised that the Formulary not be used as the sole source of information. It is strongly recommended that original references or product monograph be consulted prior to using a chemotherapy regimen for the first time.
Some Formulary documents, such as the medication information sheets, regimen information sheets and symptom management information (for patients), are intended for patients. Patients should always consult with their healthcare provider if they have questions regarding any information set out in the Formulary documents.
While care has been taken in the preparation of the information contained in the Formulary, such information is provided on an “as-is” basis, without any representation, warranty, or condition, whether express, or implied, statutory or otherwise, as to the information’s quality, accuracy, currency, completeness, or reliability.
CCO and the Formulary’s content providers shall have no liability, whether direct, indirect, consequential, contingent, special, or incidental, related to or arising from the information in the Formulary or its use thereof, whether based on breach of contract or tort (including negligence), and even if advised of the possibility thereof. Anyone using the information in the Formulary does so at his or her own risk, and by using such information, agrees to indemnify CCO and its content providers from any and all liability, loss, damages, costs and expenses (including legal fees and expenses) arising from such person’s use of the information in the Formulary.