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

CAPELAPA

Cancer Type: Breast  Intent: Palliative
Regimen Category: Evidence-Informed
Funding:
ODB - General Benefit
    capecitabine
Exceptional Access Program
    lapatinib - Second-Line treatment of HER2 positive metastatic breast cancer in combination with chemotherapy after previous exposure to trastuzumab based treatments, with specific criteria
Exceptional Access Program
    lapatinib - Treatment of HER-2 positive metastatic breast cancer when used in combination with chemotherapy after use of trastuzumab in patients who have an adverse drug reaction or contraindication to trastuzumab therapy
A - Regimen Name

CAPELAPA Regimen
Capecitabine-Lapatinib


Disease Site
Breast

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.


Rationale and Uses
  • Advanced breast cancer patients with HER2-expressing breast cancer, who have progressed on prior therapy with taxanes, anthracycline, and trastuzumab. The phase III clinical trial included only patients with good performance status. Usage is also funded for patients in whom further trastuzumab is contraindicated /not tolerated.
  • Note: A patient whose disease has progressed from first line trastuzumab and second line Kadcyla®trastuzumab emtansine will not be eligible for funding of third line “lapatinib-capecitabine” or “trastuzumab-other chemotherapy”. 

Supplementary Public Funding

capecitabine
ODB - General Benefit (capecitabine)

lapatinib
Exceptional Access Program (lapatinib - Second-Line treatment of HER2 positive metastatic breast cancer in combination with chemotherapy after previous exposure to trastuzumab based treatments, with specific criteria) (EAP Website)

lapatinib
Exceptional Access Program (lapatinib - Treatment of HER-2 positive metastatic breast cancer when used in combination with chemotherapy after use of trastuzumab in patients who have an adverse drug reaction or contraindication to trastuzumab therapy) (EAP Website)

 
B - Drug Regimen

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

(Outpatient prescription in multiples of 150mg or 500mg tablets;  *Total dose 2000 mg/m2/day)

AND

lapatinib
1250 mg PO Days 1 to 21
(Outpatient prescription in multiples of 250mg tablets)
back to top
 
C - Cycle Frequency

REPEAT EVERY 21 DAYS

Until evidence of disease progression, or unacceptable toxicity

 
D - Premedication and Supportive Measures

Antiemetic Regimen:

Low – No routine prophylaxis; PRN recommended

Other Supportive Care:

  • Supportive care should be provided, including loperamide for diarrhea.
  • Topical emollients (e.g. hand creams, udder balm) may ameliorate the manifestations of hand-foot syndrome in patients receiving capecitabine.
  • For lapatinib-induced rash, colloidal oatmeal lotion and oral antibiotics such as minocycline 100mg PO bid have been shown to be effective. Emollients may be useful for the dry skin component of this rash.
  • Patients should be advised to avoid sun exposure and use sunscreen with SPF ≥ 30.

Also refer to CCO Antiemetic Recommendations.

 
E - Dose Modifications

Electrolyte abnormalities should be corrected before starting treatment.  Doses should be modified according to the protocol by which the patient is being treated.  The following recommendations have been adapted from clinical trials or product monographs and could be considered.

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

Table A:  Suggested Dose Modifications for Lapatinib
Suggested dose levels for lapatinib are 1250 mg, 1000 mg, 750mg and 500mg.

 

Toxicity
Action*
Grade 2 hematologic

Hold until recovery and then restart at the same dose

≥ Grade 3 hematologic

Hold until recovery and then ↓ 1 dose level

≥20% decrease in LVEF from baseline OR lower than institution’s lower limit of normal, OR ≥ grade 3 symptoms

Discontinue and monitor patient closely; if after 2 weeks LVEF ≥ normal and patient asymptomatic may resume and ↓ 1 dose level. Monitor closely. If recurs, discontinue

Pneumonitis/interstitial lung disease

Hold and investigate; discontinue if ≥ Grade 3 confirmed

Severe changes in liver function
Discontinue
 
Severe skin reactions (i.e. SJS, TEN) Discontinue
Grade 1-2 diarrhea without complicating factors**

Start loperamide.  If no improvement, hold until resolution. Then restart. If recurs, ↓ 1 dose level.

Grade 1-2 diarrhea with complicating factors**
Or
Grade 3 diarrhea

Hold until ≤ grade 1; treat with loperamide. Consider IV electrolytes/hydration and antibiotics, if appropriate. When ≤ grade 1 restart with a 1 dose level ↓

Other grade 2 non-hematological

Continue, treat symptomatically. If no improvement hold until ≤ grade 1. Then restart. If recurs, ↓ 1 dose level

Other grade 3 non-hematological
Hold until ≤ grade 1 and then restart with ↓ 1 dose level
Grade 4 non-hematological
Discontinue
*Before re-treatment, major organ toxicities must recover to ≤ grade 1 within 14 days of treatment interruption; otherwise, discontinue.   **complicating factors include ↓ performance status, fever, sepsis, neutropenia, dehydration, severe cramping or nausea/vomiting

Table B:  Dosage Adjustment Table for Capecitabine

Do not start treatment with capecitabine unless baseline neutrophil counts are ≥ 1.5 x 109/L and/or platelet counts of ≥ 100 x 109/L.  Patients should be informed of the need to interrupt treatment immediately if moderate or severe toxicity occurs. Doses should not be re-escalated if reduced for toxicity. Missed or omitted doses of capecitabine should not be replaced.

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

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
 
 
 
Interrupt until resolved to grade 0-1
Interrupt until resolved to grade 0-1
Interrupt until resolved to grade 0-1 Discontinue treatment permanently
 
 
100%
75%
50%
--
 
Grade 3
1st appearance
2nd appearance
3rd appearance OR any evidence of Stevens-Johnson syndrome or Toxic Epidermal Necrolysis
 
 
Interrupt until resolved to grade 0-1
Interrupt until resolved to grade 0-1
Discontinue treatment permanently
 
 
75%
50%
--
 
Grade 4
 
 
1st appearance, including SJS, TEN, OR
cardiotoxicity, OR
acute renal failure
 
 
 
 
 
2nd appearance

 

 

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 0-1.
 

 
Discontinue permanently
 
 
 
 
Discontinue
OR
 
50%
 
 
 
 

 --



Hepatic Impairment

Hepatic impairment

Capecitabine

Lapatinib

Mild

100%

100%

Moderate

100%

Caution, consider dose ↓

Severe

No data – do not use or use with extreme caution

Use with extreme caution - ↓ dose and monitor closely

 


Renal Impairment

Creatinine Clearance (mL/min)
Capecitabine (% previous dose)
Lapatinib (% previous dose)
51-80
 
100%
(with close monitoring)
No dose adjustment appears to be required.
30-50
75%
< 30
DISCONTINUE

 


Dosage in the Elderly

No dose adjustment for the starting dose is required for capecitabine, but patients should be closely monitored and dose modification should be performed as described above. Older patients are more susceptible to the effects of fluoropyrimidine-based therapies with increased grade 3 / 4 adverse effects, especially when used in combination.

Lapatinib appears to have higher incidence of edema and an earlier onset of cardiac toxicity in patients ≥ 65 years. No dosage adjustment is recommended. 

 


 
F - Adverse Effects

Refer to capecitabine, lapatinib 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

  • Diarrhea (may be severe) 
  • Hand-foot syndrome (may be severe)
  • Rash (may be severe)
  • Nausea, vomiting
  • Mucositis
  • Increased LFTs (may be severe)
  • Fatigue
  • Headache
  • Alopecia
  • Anorexia
  • Nail disorder
  • Abdominal pain
  • Epistaxis
  • Myelosuppression +/- infection, bleeding 
  • Cardiotoxicity
  • Prolonged QT interval
  • Arrhythmia
  • Arterial / venous thromboembolism
  • GI obstruction / perforation
  • Pneumonitis
  • Hypersensitivity
  • Leukoencephalopathy
  • Eye disorders
  • Nephrotoxicity
  • ITP
 
G - Interactions

Refer to capecitabine, lapatinib drug monograph(s) for additional details


  • Avoid concomitant use with strong CYP3A4 inhibitors and inducers, if possible. If not possible, consider adjusting lapatinib dose (see drug monograph).
  • Avoid CYP3A4 substrates with narrow therapeutic indices, if possible. If not possible, consider dose adjustment of the substrate drug.
  • Avoid concomitant use with drugs that prolong the QT interval, if possible. Monitor closely if used together. 
  • Avoid concomitant use of capecitabine with sorivudine and related analogues. Wait at least 4 weeks after sorivudine treatment before starting capecitabine. 
  • Avoid concomitant administration of phenytoin; monitor phenytoin levels if used together. 
  • Caution and monitor PT, INR with warfarin.
  • Caution and monitor for reduced effectiveness of capecitabine with PPIs; consider switching to an antacid. 
 
H - Drug Administration and Special Precautions

Refer to capecitabine, lapatinib drug monograph(s) for additional details


Administration

Capecitabine:

  • Oral self-administration; drug available by outpatient prescription.
  • Clinical studies performed with capecitabine administered 30 minutes after food. Administering capecitabine on an empty stomach may result in slightly higher exposure and thus toxicity.
  • 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.

Lapatinib:

  • Oral self-administration; drug available by outpatient prescription
  • Avoid grapefruit, pomegranate, starfruit, Seville oranges and their juices/products while on lapatinib treatment
  • Take the daily dose at least 1 hour before, or at least 1 hour after a low-fat meal
  • Do not divide dose.
  • Missed doses should not be replaced; dosing should resume with the next scheduled daily dose.


Contraindications

  • Patients who have a known hypersensitivity to lapatinib, capecitabine, their excipients, or 5-fluorouracil
  • Patients with HER2 negative status given the lack of benefit in this group
  • Patients with severe renal impairment (CrCl <30 mL/min)
  • Patients with known near or complete absence of DPD (dihydropyrimidine dehydrogenase) deficiency
  • Concomitant use with sorivudine or related analogues (i.e. brivudine), given potential fatal drug interaction (see drug interactions)

Warnings / precautions:

  • Contains lactose and should not be used in patients with hereditary galactose/glucose/lactase disorders.
  • Patients with conditions that can impair left ventricular function, or in patients at risk of experiencing QT prolongation or Torsades de Pointes (females, age 65 or older, baseline QT prolongation, cardiac disease, history of arrhythmias, electrolyte disturbances, bradycardia, diabetes, concurrent drugs that prolong QT interval (see Interactions)
  • Hypokalemia, hypomagnesemia or hypocalcemia should be corrected before starting treatment
  • Patients with pre-existing diarrhea or conditions that predispose to diarrhea
  • Patients with risk factors for dehydration, pre-existing renal dysfunction or on nephrotoxic agents
  • Patients with partial DPD deficiency - use with extreme caution

Pregnancy / lactation:

  • This regimen 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.
     

 

 

 
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
  • Electrolytes; Baseline and at each visit
  • Liver and renal function tests; Baseline and at each visit
  • LVEF evaluation; Baseline and as clinically indicated
  • INR and/or PT; Baseline and regular if on anticoagulants
  • Clinical assessment for skin, GI, cardiac and pulmonary toxicities; At each visit
  • Skin examination; Before treatment and at each visit during treatment
  • Grade toxicity using the current NCI-CTCAE (Common Terminology Criteria for Adverse Events) version

Suggested Clinical Monitoring

  • ECG,  for patients at risk of developing QT prolongation; baseline and as clinically indicated

 


back to top
 
J - Administrative Information
Outpatient prescription for home administration

 
K - References

Cameron D, Casey M, Press M, et al. A phase III randomized comparison of lapatinib plus capecitabine versus capecitabine alone in women with advanced breast cancer that has progressed on trastuzumab: updated efficacy and biomarker analyses. Breast Cancer Res Treat 2008: 112: 533-43. 

Capecitabine and lapatinib drug monographs, Cancer Care Ontario.

Capri G, Chang J, Chen SC, et al. An open-label expanded access study of lapatinib and capecitabine in patients with HER2-overexpressing locally advanced or metastatic breast cancer. Ann Oncol 2010;21(3):474-80.

Geyer CE, Forster J, Lindquist D, et al. Lapatinib and capecitabine for HER2-positive advanced breast cancer. NEJM 2006; 355: 2733-43.

May 2019 Updated 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.