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Cancer Type: Breast  Intent: Palliative
Regimen Category: Evidence-Informed
Exceptional Access Program
    palbociclib TABLETS - For the treatment of post-menopausal women with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative unresectable locally advanced breast cancer or metastatic breast cancer, according to clinical criteria
ODB - General Benefit
A - Regimen Name


Disease Site


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

For the treatment of hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative locally advanced or metastatic breast cancer as initial endocrine-based therapy in postmenopausal women.

Supplementary Public Funding

Exceptional Access Program (palbociclib TABLETS - For the treatment of post-menopausal women with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative unresectable locally advanced breast cancer or metastatic breast cancer, according to clinical criteria) (EAP Website)

ODB - General Benefit (letrozole) (ODB Formulary )

B - Drug Regimen

125 mg PO Days 1 to 21

available in 75, 100 and 125 mg capsules

2.5 mg PO Daily

available in 2.5 mg tablets

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C - Cycle Frequency

Palbociclib: REPEAT EVERY 28 DAYS


Until disease progression or unacceptable toxicity

D - Premedication and Supportive Measures

Antiemetic Regimen:

Minimal – No routine prophylaxis; PRN recommended

Febrile Neutropenia Risk:


Other Supportive Care:

Also refer to CCO Antiemetic Recommendations.

E - Dose Modifications

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

Letrozole: No dosage adjustment necessary for hematological and/or non-hematological toxicities.

Dosage with toxicity

Dose levels:

Dose level Palbociclib dose (mg/day) for 3 out of 4 weeks Letrozole dose (mg/day) continuous
0 125 2.5
-1 100 2.5
-2 75 2.5
-3 If further dose reduction required, discontinue 2.5

Do not retreat until ANC ≥ 1 x 109/L, platelets ≥ 50 x 109/L and non-hematologic toxicities have returned to baseline or Grade ≤ 1 (or at physician discretion,  Grade ≤ 2, if not considered a patient safety risk). If conditions are not met, palbociclib should be delayed by 1 week, but letrozole may be continued. If no recovery after 2 weeks, discontinue palbociclib.




Palbociclib Dose



Day 1: Hold and repeat CBC within 1 week. When recovered to Grade ≤ 2, re-start next cycle at same dose.

Day 15 of 1st 2 cycles: Continue current dose to complete the cycle. Repeat CBC day 22.

If Grade 4 on Day 22, see Grade 4 recommendation below.

Consider dose reduction if > 1 week recovery or recurrent Grade 3 neutropenia in subsequent cycles.


3 with fever ≥ 38.5oC and/or infection

Hold until recovery to Grade ≤ 2. Restart at the next lower dose.



Hold until recovery to Grade ≤ 2. Restart at the next lower dose.


3 or 4 (if persisting despite medical treatment)

Hold until recovery to Grade ≤ 1 or Grade ≤ 2 (if not considered a safety risk). Restart at the next lower dose.

Hepatic Impairment

  • Mean fraction of unbound palbociclib in plasma increases with worsening hepatic function. 

Hepatic Impairment



Mild - Moderate (Child-Pugh class A and B)

No dosage adjustment needed.

No dosage adjustment needed.

Severe (Child-Pugh class C)

75 mg once daily (days 1 to 21; q28 days). Monitor for toxicity.

No data in severe hepatic impairment. Monitor closely and consider dose modification.

Renal Impairment

Palbociclib: No dose adjustment is required.

Letrozole: No dose adjustment is required.


Dosage based on gender:

Gender and body weight had no significant effect on palbociclib exposure.

Dosage in the Elderly

No dosage adjustment required for either palbociclib or letrozole.  Patients ≥ 65 were more likely to experience anemia in clinical trials. Older patients may have an increased risk of osteoporosis and fracture with letrozole.


Dosage based on ethnicity

A pharmacology study in healthy volunteers indicated that bioavailability of palbociclib is higher (AUC 30%, Cmax 35%) in Japanese subjects compared to non-Asian subjects. No dose modification is needed.

F - Adverse Effects

Refer to palbociclib, letrozole 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

  • Myelosuppression +/- infection, bleeding (may be severe)
  • Estrogen deprivation symptoms (e.g. hot flashes, osteoporosis)


  • Fatigue
  • Musculoskeletal pain
  • Headache
  • Edema
  • Mucositis
  • Nausea, vomiting


  • Increased cholesterol
  • Alopecia
  • Dizziness
  • Diarrhea
  • Constipation
  • Anorexia
  • Insomnia
  • Cough, dyspnea
  • Rash


  • Arterial thromboembolism
  • Venous thromboembolism
  • Arrhythmia
  • Cardiotoxicity
  • Hypersensitivity
  • Eye disorders
G - Interactions

Refer to palbociclib, letrozole drug monograph(s) for additional details

  • Palbociclib is a substrate and weak inhibitor of CYP3A and moderate substrate of P-gp.

  • Avoid strong CYP3A inhibitors due to increased risk of palbociclib exposure.
  • Avoid strong and moderate CYP3A inducers that may decrease palbociclib exposure. If moderate CYP3A inducers cannot be avoided, no dose adjustment of palbociclib is needed.

  • Palbociclib capsules should be given with food to reduce variable drug exposure and minimize drug interactions with drugs that alter gastric pH.

  • Consideration should be given to reducing the dose of CYP3A substrates with narrow therapeutic indices (e.g. cyclosporine).

  • Letrozole is a strong inhibitor of CYP2A6 and moderate inhibitor of CYP2C19. Caution is advised when administered with drugs with a narrow therapeutic index that are mainly metabolized by these isoenzymes (e.g. phenytoin, clopidogrel).

  • Avoid concomitant use with tamoxifen and other anti-estrogens or estrogen-containing therapies.

  • Avoid grapefruit, starfruit, Seville oranges or their juices/products while on this treatment, since this may increase side effects.

H - Drug Administration and Special Precautions

Refer to palbociclib, letrozole drug monograph(s) for additional details.

Administration: palbociclib

  • Palbociclib capsules should be administered with food; palbociclib tablets may be given with or without food.
  • Capsules or tablets should be swallowed whole and not chewed, crushed, opened, or split prior to administration.
  • If a patient vomits or misses a dose, an extra dose should not be taken to make up for the vomited or missed dose. The next dose should be taken at the usual time.
  • Grapefruit, pomegranatestarfruit, Seville oranges, their juices or products should be avoided during palbociclib treatment.
  • Capsules should be stored at 20 to 25oC, with excursions permitted between 15 to 30oC. Tablets should be stored at 15 to 30oC in original packaging to protect from moisture.

Administration: letrozole

  • Tablets should be taken with a glass of water, with or without food, at around the same time every day.

  • Do not crush or chew the tablets.

  • Missed doses should be taken as soon as possible, but should be skipped if within a few hours of the next planned dose.  Do not double the dose due to over-proportionality of exposure at doses above 2.5 mg daily.

  • Store tablets at room temperature (15-30°C).



  • Patients who are hypersensitive to palbociclib, letrozole or any of their components.

  • Premenopausal women and patients under 18 years of age.

  • In pregnancy or lactation.

  • Not indicated in hormone-receptor negative disease.


Other Warnings/Precautions:

  • As fatigue and dizziness have been reported with palbociclib, patients should exercise caution when driving or operating machinery.

  • Palbociclib contains lactose; carefully consider use in patients with hereditary galactose intolerance, severe lactase deficiency or glucose-galactose malabsorption.


Pregnancy and Lactation:

  • Palbociclib and letrozole should not be used in pregnancy.  If treatment is used in women of childbearing potential, adequate contraception should be used by both sexes during treatment, and for at least 3 weeks after the last dose.

  • Breastfeeding is not recommended with palbociclib.

  • Animal data suggests that palbociclib may affect male fertility. Although not approved for use in men, sperm preservation should be considered prior to starting treatment in males. Male patients with female partners of reproductive potential should use effective contraception during treatment and at least 97 days after the last dose


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 before each cycle, on day 15 of the first 2 cycles, one week after Grade 3 neutropenia, and as clinically indicated. If Grade ≤ 2 neutropenia in the first 6 cycles, may monitor every 3rd cycle thereafter. 

  • Liver function tests; Baseline and as clinically indicated.

  • Renal Function tests; Baseline and as clinically indicated.

  • Serum cholesterol and lipids evaluation; Baseline and regular.

  • Bone mineral density; Baseline and regular.

  • Clinical toxicity assessment for estrogen withdrawal symptoms, infection, bleeding, thromboembolism, fatigue, rash, eye problems, GI, musculoskeletal effects; At each visit.

  • 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

Letrozole and palbociclib drug monographs, Cancer Care Ontario

Finn RS, Crown JP, Lang I, et al. The cyclin-dependent kinase 4/6 inhibitor palbociclib in combination with letrozole versus letrozole alone as first-line treatment of oestrogen receptor-positive, HER2-negative, advanced breast cancer (PALOMA-1/TRIO-18): a randomised phase 2 study. Lancet Oncol. 2015 Jan;16(1):25-35.

November 2020 Modified Drug administration (palbociclib) and Interactions sections

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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.
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.