PA30326 Workshop Metastatic Flashcards
Mrs MM, a 60-year-old post-menopausal female, had been treated for early breast cancer (ER/PR +ve, HER2 -ve) at the age of 52. She had undergone a wide local excision (lumpectomy) and post surgery had received chemotherapy and radiotherapy. She had then taken anastrozole for 5 years.
She presented to her GP at the age of 62 with increasing lethargy, mild back pain and some intermittent pain in the right upper quadrant. She underwent investigations including a CT scan of chest, abdomen and pelvis which showed multiple bony metastases in her spine and small volume liver metastases.
The Consultant Oncologist decides that as Mrs MM is not experiencing life-threatening symptoms from her disease, she does not need to start chemotherapy treatment yet. Instead she can be prescribed a combination of palbociclib and letrozole.
What is the mechanism of action of palbociclib?
- It Is a CDK4/6 (cycline dependent kinase) inhibitor
- Tumour cell proliferation in many in many breast cancers is underpinned by hyperactivity of the CDK 4/6 axis
- Activation of CKD 4/6 usually promotes progression of the cell cycle to the S phase
CKD 4/6 inhibitors particularly prevent cell cycle progression from G1 to S Phase of cell cycle
Different CDK4/6 inhibitors have different affinities for CDK4 and CDK6, therefore side effects vary slightly between Palbociclib, Ribociclib & Abemaciclib
Letrozole is an aromatase inhibitor. How do these work in breast cancer?
Aromatase inhibitor inhibit action of aromatase, an enzyme which converts androgens into oestrogens.
Aromatase is only present in peripheral tissues (skin, fat, muscle)
They only work in post-menopausal women (or women without functioning ovaries) as pre-menopause, most of the body’s oestrogen is produced by ovaries and production of oestrogen in ovaries is too high for the AI to be effective
Some breast cancers are stimulated to grow by oestrogen (ER +ve) approx 75% of breast cancers
Palbociclib was approved by NICE for use in the NHS in 2017, based on the fact that it improves progression-free survival (PFS) when used as
1st line treatment in ER/PR +ve, HER2 -ve metastatic breast cancer,
compared to letrozole alone. PFS was 30 months for palbociclib +
letrozole, 19 months for letrozole alone. This can significantly increase
the time until patients require chemotherapy treatment with its
associated side effects, therefore improving quality of life.
What is the starting dose of palbociclib and how should the patient take it?
- 125mg PO daily for 3 weeks
- then, 1 week off
- Swallow capsules whole with food
- Take dose at approx same time each day
- No grapefruit/grapefruit juice
What are the common side effects of palbociclib?
- Neutropenia, Anaemia, thrombocytopenia
- Infections
- Fatigue
- N & V
- Stomatitis
- Rash, dry skin
- Alopecia (hair loss)
- Diarrhoea
Mrs MM comes back to clinic 4 weeks after starting palbociclib. She is
seen by the Pharmacist Prescriber who ascertains that she is tolerating
the treatment well with no side effects. However her full blood count in
clinic shows neutrophils of 0.6 (normal range 2-7.5).
Should she proceed with her next cycle of palbociclib (due to start the next day)? If not, what action should the pharmacist take?
No, delay treatment until neuts >1, then start next cycle at same dose
Mrs MM’s neutrophil count recovers the following week to 1.5 and she
proceeds with cycle 2 palbociclib. She continues on the drug for 3 years
with CT scans every 3 months to assess response. Palbociclib
controlled her cancer for 3 years but then a CT scan showed disease
progression, with an increase in the number of liver metastases and
bone metastases.
She also started to feel more lethargic and was suffering aches and
pains in her back. The Consultant Oncologist discusses with her the
need to start chemotherapy to treat her cancer.
As Mrs MM was treated with chemotherapy when she was first
diagnosed with breast cancer aged 52, it is important to know what
drugs she received then, as there is a maximum lifetime dose of
anthracyclines e.g. epirubicin, doxorubicin.
Why is there a maximum lifetime dose of anthracyclines? What is the maximum lifetime dose of epirubicin (mg/m2)?
- Epirubicin 900mg/m^2
- Increased risk of cardiotoxicity
: arrhythmias and cardiomyopathy including life-threatening congsetive heart failure
The pharmacist checks the patient’s records and finds out that she
received 6 cycles of FEC 100 chemotherapy (fluorouracil, epirubicin
100mg/m2 and cyclophosphamide) when she was originally treated for
breast cancer.
The Consultant Oncologist decides not to use an anthracycline and
prescribes Mrs MM weekly paclitaxel chemotherapy (6 cycles, 21 day
cycle length) instead.
How much epirubicin has Mrs MM received, assuming she stayed on the full dose for her 6 cycles of chemotherapy?
600mg/m^2
What sort of signs & symptoms might a patient exhibit if they were having a hypersensitivity reaction to paclitaxel? What premeds are used to try to prevent this reaction?
- Mild-flushing of skin, itching
- Severe hypotension, bronchospasm, generalised rash/erythma
To prevent this
- Chlorphenamine 10mg IV
- Ranitidine 50mg IV
- Dexamethason 8mg IV
What antiemetics would be appropriate for this chemotherapy?
Moderately emetogenic – dexamethasone 8mg PO/IV & ondansetron
8mg PO/IV pre-chemo
Then dex 8mg PO daily for 2 days + domperidone 10mg tds prn (for 5
days)
- Moderately emetogenic
Dexamethasone 8mg PO/IV & Ondansetron 8mg PO/IV pre-chemo
Then, Dexamethasone 8mg PO daily for 2 days + domperidone 10mg tds prn (for 5 days)
- One of the common side effects of paclitaxel is peripheral neuropathy. What dose modification should be made if a patient suffers from grade 2 peripheral neuropathy (i.e. moderate symptoms that interfere/limit daily activities)?
- Reduce Paclitaxel dose to 70mg/m^2 (usually 80mg/m^2)
Mrs MM completes 6 cycles of weekly paclitaxel and her disease
remains under control for a further 6 months. Then she begins to feel
more unwell with more bone pain. She does not feel she wishes to have
further intravenous chemotherapy, so the Consultant Oncologist
suggests trying capecitabine, an oral chemotherapy agent, to relieve her
symptoms and prolong survival.
What drug is capecitabine a prodrug of?
- Fluorouracil
What do you think are the advantages and disadvantages of oral and intravenous chemotherapy?
Oral advantages
- patient can administer themselves at home, gives them control over their treatment
- no issues with infection risk from venepuncture
- easier & quicker for Pharmacy to prepare, no sterility/short expiry date issue
Oral disadvantage
- relies on patient to take correct dose
- patient may feel isolated
- not good for patients with swallowing difficulties
IV advantages
- know correct dose has been administered as given in hospital
- patienet can talk to other patients in similar situation and obtain support from Chemo nurses
IV disadvantages
- risk of infection with having venepuncture
- time-consuming for patients as has to be administered in hospital
- some patients difficult to cannulate
- time-consuming for pharmacy to prepare in aseptic unit
- some drugs have very short expiry so cannot be prepared in advance
If you were the pharmacist handing out Mrs MM’s capecitabine, how would you tell her to take it?
- Twice a day with water (after breakfast and evening meal)
- 8-12 hr gap between doses
- Take for 14 days then have 7 days off
She mentions that she is taking a vitamin supplement containing vitamins A, B, C, D, E, folic acid and selenium. Is this OK to take with capecitabine?
No, folic acid increases toxicity from capecitabine.
What dose should she be prescribed if she was 1.61m2 and receiving 100% dose?
2000mg bd
