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LETR

Cancer Type: Breast  Intent: Adjuvant
Regimen Category: Evidence-Informed
Funding:
ODB Limited Use
  • letrozole - As an alternative to tamoxifen for the adjuvant treatment of postmenopausal women with hormone receptor positive early breast cancer for a maximum of five years
ODB Limited Use
  • letrozole - Treatment of hormone receptor positive early breast cancer in postmenopausal women who have received 5 years of adjuvant tamoxifen therapy
A - Regimen Name

 

LETR Regimen
Letrozole

 

 

Disease Site
Breast

 

 

Intent
Adjuvant

 

 

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

Adjuvant treatment in postmenopausal women with hormone-receptor positive invasive early breast cancer* (Health Canada indication)
or
Extended adjuvant treatment in postmenopausal women with hormone-receptor positive invasive early breast cancer, after 5 years of tamoxifen treatment (Health Canada indication)

The Breast Clinical Practice Guideline (2014) recommends an aromatase inhibitor be used in postmenopausal patients with ER+ breast cancer (may have received adjuvant chemotherapy). Acceptable strategies for the use of the aromatase inhibitor include upfront treatment, switch strategy or extended adjuvant therapy.

*Aromatase inhibitors (AIs) have been used in the neoadjuvant setting in some clinical trials; AIs generally demonstrated higher breast conserving surgery rates with superior or similar response rates to tamoxifen. However, neoadjuvant AI use has not been approved by Health Canada

 

 

Supplementary Public Funding

letrozole
ODB Limited Use (letrozole - As an alternative to tamoxifen for the adjuvant treatment of postmenopausal women with hormone receptor positive early breast cancer for a maximum of five years)
 

letrozole
ODB Limited Use (letrozole - Treatment of hormone receptor positive early breast cancer in postmenopausal women who have received 5 years of adjuvant tamoxifen therapy)
 

 

 
B - Drug Regimen

 

letrozole
 
2.5 mgPODaily

(Outpatient prescription in 2.5 mg tablets)

For extended adjuvant therapy, start within 3 months of completion of approximately 5 years of tamoxifen

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C - Cycle Frequency

 

CONTINUOUS TREATMENT

Unless disease progression or unacceptable toxicity

Upfront treatment:  For 5 years
Switch strategy:  For 2-3 years (as a switch after 2-3 years of tamoxifen) for a total of 5 years of endocrine therapy
Extended adjuvant therapy:  For 3-5 years, after completing 5 years of tamoxifen

 

 
D - Premedication and Supportive Measures
 
Antiemetic Regimen:

Not applicable

Other Supportive Care:

Patients receiving adjuvant letrozole should ensure adequate calcium intake (with supplementation as needed) and vitamin D supplementation. For more information about bone health via dietary and lifestyle measures, see pamphlet on Bone Health in Post-Menopausal Women.
 
E - Dose Modifications

 

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.

 

Dosage with toxicity

 

Dosage in myelosuppression: No dosage adjustment required.

 

 

Hepatic Impairment

Hepatic Impairment
Dose
Mild to moderate

No dose adjustment needed, although exposure may ↑ by 37%

Severe
No data. Monitor patients closely and consider dose modification.
 

Renal Impairment

Creatinine clearance

Dose
≥ 10 mL/min
No dose adjustment needed
< 10 mL/min
No data. Consider potential benefit-risk carefully.
 
F - Adverse Effects
Refer to letrozole drug monograph(s) for additional details of adverse effects
 

Most Common Side Effects 

Less Common Side Effects, but may be
Severe or Life-Threatening

  • Estrogen withdrawal symptoms
  • Fatigue
  • Headache, musculoskeletal pain
  • Edema
  • ↑ Cholesterol
  • Dizziness
  • Constipation
  • Nausea / vomiting
  • Osteoporosis, fracture
  • Arrhythmia
  • Rash
  • Arterial thromboembolism
  • Venous thromboembolism
  • Cardiotoxicity
  • Cataracts
  • Hypersensitivity

 

 
G - Interactions
Refer to letrozole drug monograph(s) for additional details
 
H - Drug Administration and Special Precautions
Refer to letrozole drug monograph(s) for additional details
 
I - Recommended Clinical Monitoring

Recommended Clinical Monitoring

  • Bone mineral density; baseline and regular
  • LH, FSH and/or estradiol levels in patients whose menopausal status is unclear or who become amenorrheic after chemotherapy; before starting letrozole and regularly during the first 6 months of treatment. Only confirmed postmenopausal patients should receive letrozole.;
  • Serum cholesterol and lipids evaluation; baseline and regular
  • Clinical assessment of fatigue, estrogen withdrawal symptoms, musculoskeletal, cardiovascular, thromboembolism, GI and GU effects, ophthalmic, etc.; regular
  • Grade toxicity using the current NCI-CTCAE (Common Terminology Criteria for Adverse Events) version

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J - Administrative Information
Outpatient prescription for home administration
 
 
 
K - References

BIG 1-98 Collaborative Group, Mouridsen H, Giobbie-Hurder A, et al. Letrozole therapy alone or in sequence with tamoxifen in women with breast cancer. N Engl J Med 2009;361(8):766-76.

Eiermann W, Paepke S, Appfelstaedt J, et al.  Preoperative treatment of postmenopausal breast cancer patients with letrozole: A randomized double-blind multicenter study.  Ann Oncol 2001;12(11):1527-32.

Ellis MJ, Coop A, Singh B, et al. Letrozole is more effective neoadjuvant endocrine therapy than tamoxifen for erbB-1– and/or erbB-2–positive, estrogen receptor–positive primary breast cancer: evidence from a phase III randomized trial. J Clin Oncol 2001;19(18):3808-16.

Goss PE, Ingle JN, Pater JL, et al.  Late extended adjuvant treatment with letrozole improves outcome in women with early-stage breast cancer who complete 5 years of tamoxifen. JCO 2008;26(12):1948-55.

Goss P, Ingle J, Martino S, et al.  A randomized trial of letrozole in postmenopausal women after five years of tamoxifen therapy for early-stage breast cancer.  NEJM 2003;349(19):1793-802.

Regan MM, Neven P, Giobbie-Hurder A, et al. Assessment of letrozole and tamoxifen alone and in sequence for postmenopausal women with steroid hormone receptor-positive breast cancer: the BIG 1-98 randomised clinical trial at 8·1 years median follow-up. Lancet Oncol 2011;12(12):1101-8.

 

October 2017 removed sub-site adjuvant (under intent)

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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.
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Regimen Monographs
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