5 - Oral Anti-cancer Education

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Online registration form
Name, AHPRA number, years practicing as a registered pharmacist, email address, approximate
number of oral anti-cancer prescriptions dispensed each month, tick what the prescriptions are for.
Instructions and learning objectives
Introduction
Oral formulations of anti-cancer chemotherapy have been used for decades including
cyclophosphamide, melphalan and tamoxifen; however, recent years have seen a rapid expansion in
oral cancer treatments. Approximately 25% to 35% of all antineoplastic agents in development in
2013 are oral formulations with a focus on cytotoxic agents, small-molecule inhibitors and receptor
targeted agents.1 This paradigm shift from intermittent IV infusions in oncology units to oral dosing
in the patient’s home has significant implications for the provision of medications and adherence to
dosing regimens.
There are numerous advantages of oral chemotherapy including enhanced flexibility for patients and
increased convenience.2 Other benefits over intravenous (IV) therapy included no risk of
extravasation, bleeding, venous thromboembolism, infection and no need for venous access
devices.3
Pharmacists are uniquely placed to provide patients with education regarding medications,
particularly due to their knowledge and regular interaction with patients. Given the number of oral
anti-cancer agents available on the Pharmaceutical Benefits Scheme (PBS) in Australia, the provision
of patient education will often fall to community pharmacists. This education module is designed to
highlight important counselling points for several of the more common oral anti-cancer medications.
Multiple choice questions accompany this education module for the purpose of assessing whether
targeted education may enhance community pharmacists’ knowledge and confidence in dispensing
anti-cancer medications.
Novadex-D® (tamoxifen) is a selective oestrogen receptor modulator for treatment of hormone
receptor-positive breast cancer.AMH Patient MB is a new customer at your pharmacy and she wishes
to have all her prescriptions dispensed, including tamoxifen.
Which of the following medications presents a potential drug interaction with tamoxifen, through
inhibition of its metabolism by CYP2D6?
a.
b.
c.
d.
St John’s Wort
Erythromycin
Phenytoin
Paroxetine
How certain are you?
1: not very; it’s a guess 2: moderately 3: very certain
The correct answer is d. The metabolism of tamoxifen to the active metabolite, endoxifen, relies
primarily on CYP2D6. Any drugs that are strong inhibitors of CYP2D6 such as paroxetine and
fluoxetine, may reduce the effectiveness of tamoxifen. Pharmacists should notify health care
practitioners if patients are using concurrent tamoxifen and a strong inhibitor of CYP2D6 to ensure
optimal outcomes.AMH
Patient MB has been taking tamoxifen for a few years and would like to know more about the side
effects of this medication. Which of the following are adverse effects of tamoxifen?
a. Elevated triglyceride levels, increased risk of thromboembolic events and increased
incidence of endometrial changes
b. Increased risk of cardiovascular events, peripheral neuropathy and conjunctivitis
c. Increased incidence of squamous cell carcinoma, haemolytic uraemic syndrome and
increased risk of uterine sarcoma
d. Cataracts, hypokalaemia and increased incidence of aplastic anaemia
How certain are you?
1: not very; it’s a guess 2: moderately 3: very certain
The correct answer is a. Tamoxifen competes with oestrogen for receptor sites in breast tissue to
inhibit tumour growth, but also has an oestrogen agonist activity on endometrium, bone and
lipids.AMH
Patient EF presents to your community pharmacy with a prescription for Xeloda® (capecitabine)
2000mg mane and 2500mg nocte. What class of oral chemotherapy medication is capecitabine?
a.
b.
c.
d.
Kinase inhibitors
Alkylating agents
Antimetabolites
Topoisomerase inhibitors
How certain are you?
1: not very; it’s a guess 2: moderately 3: very certain
The correct answer is c. Capecitabine is an antimetabolite along with fludarabine, methotrexate and
mercaptopurine. Capecitabine itself is noncytotoxic. It is a pro-drug converted to the cytotoxic
moiety, fluorouracil (5-FU) by thymidine phosphorylase, an enzyme in tumours.mims
On questioning Patient EF tells you she has been diagnosed with colorectal cancer and her
oncologist has given her this prescription. What is the dose of capecitabine recommended for the
treatment of colorectal cancer?
a.
b.
c.
d.
1250mg/m2 BD on Days 1 to 14 every 21 days
1250mg/m2 BD
1000mg/m2 BD on Days 1 to 14 every 21 days
1000mg/m2 BD
How certain are you?
1: not very; it’s a guess 2: moderately 3: very certain
The correct answer is a. For metastatic colorectal cancer, it is recommended that capecitabine is
dosed at 1250mg/m2 BD on Days 1 to 14 every 21 days. eviq Pharmacists should note that not all oral
chemotherapy medications are administered on a daily basis. Certain medications are needed for
only a few days per cycle or with planned drug-free intervals. When prescribed for colon cancer the
typical capecitabine regimen is administered for 2 weeks of every 3-week cycle (2 weeks on followed
by 1 week off). Capecitabine is also used in a number of other cancers including breast, colon and
oesphagogastric which may require different treatment protocols. EVIQ is a great resource of anticancer protocols. It is an online service of the cancer institute of NSW and access is free simply click
on the link to register.
Medication errors can occur when patients are unsure of when to take their medication, especially
when refilling a prescription. A specific administration schedule is helpful and early refills should be
questioned as they may represent an incorrect dosing schedule. Other examples of oral
chemotherapy medications which are sometimes prescribed with drug-free intervals include Sutent®
(sunitinib) for metastatic renal cell carcinoma and Temodal® (temozolamide) for glioblastoma
multiforme (an aggressive brain tumour).These protocols can also be accessed on the EVIQ website.
Patient EF returns to your pharmacy for the repeat dispensing of her capecitabine. She is responding
to therapy and is feeling well, except for a slight tingling in the palms of her hands. Your assessment
and advice include:
a. Apply cold packs to her hands, and ask the physician to reduce her dose.
b. Ask the physician to stop capecitabine and consider changing EF to another regimen.
c. Encourage EF to continue therapy monitor the tingling, and report any worsening of
symptoms.
d. Thoroughly review EF’s medication list because capecitabine is not associated with this
symptom.
How certain are you?
1: not very; it’s a guess 2: moderately 3: very certain
HFS is a skin reaction that appears on the palms of the hands and the soles of the feet after
administration of some medications. HFS should not be confused with hand-foot-and-mouth
disease, which is a virus that causes sores in the mouth as well as on the hands and feet. HFS is also
known as palmer-planter erythrodysesthesis. The pathophysiology of HFS is unknown. Some
theories suggest that the drug accumulates in the keratinocytes or that it might be eliminated by the
sweat glands. Most cases of HFS develop during the first 3 cycles of capecitabine and the reaction
appears to be dose-dependent. Although not usually life-threatening, HFS can have a negative
impact on quality of life. test your knowledge
The correct answer is c. Patient EF should be encouraged to continue therapy, but to continue to
monitor the tingling and report any worsening of symptoms. Tingling without other symptoms is a
grade 1 hand-foot syndrome and dose reduction is not recommended. EF should be monitored for
any worsening of symptoms because higher grade hand-foot syndrome will necessitate disruption of
therapy and/or dose reduction. test your knowledge
Patient BW is a regular customer at your community pharmacy. You know that he has been receiving
chemotherapy treatment for metastatic prostate cancer. He presents with TWO prescriptions. The
first is for Zytiga® (abiraterone) 1000mg daily.
For metastatic prostate cancer, androgen deprivation therapy is usually considered first line
treatment. This is achieved either surgically (bilateral orchiedectomy) or medically via the use of
GNRH agonists or GNRH antagonists either alone or in combination with antiandrogens.
Unfortunately most hormone dependent cancers become refractory to therapy after a period of
time, and are known as ‘castration resistant prostate cancer (CRPC)’ or ‘hormone refractory’. While
they are no longer responsive to the initial androgen deprivation therapy regimens, these cancers
still show some reliance upon androgen-based pathways to drive tumour growth.RGH bulletin
What is the mechanism of action of abiraterone acetate?
a. Selectively and potently inhibits CYP17, reducing androgen synthesis in testicular, adrenal
and prostate tumour tissues
b. Inhibits gonadotrophin production, reducing testicular androgen synthesis
c. Suppresses testicular steroidogensis by inhibiting gondaotropin production
d. Competitively inhibits the binding of androgen at androgen receptors
How certain are you?
1: not very; it’s a guess 2: moderately 3: very certain
The correct answer is a. AMH
The inhibition of androgen biosynthesis, by abirterone, can cause a compensatory increase in
adrenal mineralocorticoid production, ultimately leading to peripheral oedema, hypertension and
hypokalaemia. RGH bulletin The second prescription for Patient BW is indicated to reduce this
physiological response. What is the second prescription?
a.
b.
c.
d.
Tritace® (rampril) 1.25mg daily
Aldactone® (spironolactone) 12.5mg mane
Maxalon® (metoclopramide) 10mg tds prn
Panafcortelone® (prednisolone) 10mg mane
How certain are you?
1: not very; it’s a guess 2: moderately 3: very certain
The correct answer is d. Abiraterone causes mineralcorticoid excess resulting in fluid retention (eg
peripheral oedema), hypokalaemia and hypotension. Although the incidence and severity of these
effects are reduced by using abiraterone with a corticosteroid (eg prednisolone), they are still
common. Thus monitoring of blood pressure, potassium concentration and fluid retention are
important for Patient BW, and any patient taking abiraterone. AMH
Patients treated with abiraterone require detailed counselling regarding administration of this
medication. You instruct Mr BW to:
a.
b.
c.
d.
Take ONE tablet at night with food
Take FOUR tablets once daily on an empty stomach, 1 hour before or 2 hours after food
Take FOUR tablets in the morning with food
Take as directed by his doctor
How certain are you?
1: not very; it’s a guess 2: moderately 3: very certain
The correct answer is b. There is up to a 17-fold difference in drug exposure when taken with food,
potentially resulting in serious side effects. Abiraterone should be taken on an empty stomach, at
least TWO hours after eating and no food should be consumed for an hour after. RGH bulletin
Patient CC has Non Small Cell lung cancer (NSCLC) which has failed to respond to first line
chemotherapy treatment. His doctor has given him a prescription for Tarceva® (erlotinib) 25mg
daily.
What is the usual dosage of erlotinib for NSCLC?
a.
b.
c.
d.
Erlotinib 25mg daily
Erlotinib 100mg BD
Erlotinib 150mg daily
This medication is not indicated for non small cell lung cancer
How certain are you?
1: not very; it’s a guess 2: moderately 3: very certain
The correct answer is c. Erlotinib is a tyrosine kinase inhibitor PBS indicated for the treatment of
locally advanced NSCLC with activating epidermal growth factor receptor (EGFR) mutations after
failure of prior chemotherapy. The recommended dose is erlotinib 150mg daily. Erlotinib should be
taken on an empty stomach, ONE hour before or TWO hours after food.
Tyrosine kinase inhibitors, like erlotinib, have a number of interactions including:
a.
b.
c.
d.
Proton pump inhibitors
Lipidil® (fenofibrate)
Cigarette smoking
All of the above
How certain are you?
1: not very; it’s a guess 2: moderately 3: very certain
The correct answer is d. By increasing gastric pH, proton pump inhibitors, H2 receptor antagonists
and antacids reduce the absorption of erlotinib and the combination should be avoided if possible.
Fenofibrate may decrease erlotinib concentration and clinical efficacy. Avoid fenofibrate or increase
erlotinib dose and monitor carefully for toxicity. Cigarette smoking can increase the metabolism of
erlotinib reducing the patients’ exposure to the drug. Smokers should be advised to stop smoking
and pharmacists should offer smoking cessation.
Patient CC represents to your pharmacy with a prescription for Iressa® (gefitinib) also a tyrosine
kinase inhibitor. On questioning you discover that he was directed to stop erlotinib by his doctor due
to a severe rash suggestive of Stevens-Johnson syndrome.
Gefitinib was registered on the PBS in January 2014 for locally advanced or metastatic NSCLC. If
patients have previously been prescribed a tyrosine kinase inhibitor they must have developed and
intolerance necessitating permanent treatment withdrawal to meet PBS authority guidelines. The
severe rash Mr CC developed to erlotinib meets this requirement.
What other serious adverse effects (Grade 3 or 4) occur with tyrosine kinase inhibitors, including
erlotinib and gefitinib?
a. Interstitial lung disease
b. Fatigue
c. Anorexia
d. All of the above
How certain are you?
1: not very; it’s a guess 2: moderately 3: very certain
The correct answer is d. Tyrosine kinase inhibitors are associated with severe interstitial lung disease
which may be fatal. Patients should be advised to report any suddenly worsening dyspnoea. Fatigue
and metabolic disorders such as anorexia can also occur with tyrosine kinase treatment.
Patient MV is a 30 year old female who is due to start radiotherapy in 2 weeks for glioblastoma (an
aggressive brain tumour). She presents to your pharmacy with a prescription for Temodal®
(temozolamide) 140mg daily for 42days. When should she start taking this medication?
a.
b.
c.
d.
Today
When she starts radiotherapy
When she finishes radiotherapy
This medication is not indicated for use in glioblastoma
How certain are you?
1: not very; it’s a guess 2: moderately 3: very certain
The correct answer is b.Temozolamide is an alkylating agent indicted for the treatment of
glioblastoma multiforme with concurrent radiotherapy this is considered the concomitant phase.
The concomitant phase of treatment starts with both radiotherapy and temozolamide, hence Mrs
MV should start this medication on the day she starts radiotherapy. This phase is often followed by
the adjuvant phase where temozolamide is continued after radiotherapy has stopped and
sometimes temozolamide is used in the recurrent setting.
Patient MV is recently married and inquires whether taking this medication will affect her chances of
falling pregnant. Which of the following is true for temozolamide?
a.
b.
c.
d.
Temozolamide doesn’t affect fertility and can be taken while trying to conceive
Temozolamide disrupts the menstrual cycle and will make conception more difficult
Temozolamide may be teratogenic and patients should be advised to avoid pregnancy
Temozolamide interacts with oral contraceptives and additional measures may be required
to prevent pregnancy.
How certain are you?
1: not very; it’s a guess 2: moderately 3: very certain
The correct answer is c. There are no studies of temozolamide in pregnant women. In nonclinical
studies in rats and rabbits teratogenicity and/or foetal toxicity were demonstrated at doses below
that anticipated in humans. Temozolamide, therefore, should not be administered to pregnant
women. If use during pregnancy must be considered, the patient should be apprised of the potential
risk to the foetus. Women of childbearing potential should be advised to avoid pregnancy if they are
going to receive temozolamide treatment and for six months after discontinuation of temozolamide
therapy.
Due to the side effects of temozolamide, which of the following medications is/are usually coprescribed?
a.
b.
c.
d.
Somac® (pantoprazole or other proton pump inhibitor) for dyspepsia
Bactrim DS® (sulfamethoxazole/trimethoprim) for opportunistic infections
Zofran® (ondansetron or other antiemetics) for nausea and vomiting
All of the above
How certain are you?
1: not very; it’s a guess 2: moderately 3: very certain
The correct answer is d. Temozolamide is associated with dyspepsia and patients may also be
prescribed a proton pump inhibitor. Rare cases of opportunistic infections including pnemocytsis
carinii pneumonia have been reported. Prophylaxis with sulfamethoxazole/trimethoprim is often coprescribed. Nausea and vomiting are very commonly reported side effects of temozolamide and it is
recommended that patients receive prophylactic antimetic medications, such as ondansetron.
Patients’ should be counselled to take temozolamide at least one hour before food and that if
vomiting occurs after the dose is administered, a second dose should not be administered that day.
Patient TJ has recently commenced on a ‘new’ medication, Tafinlar® (dabrafenib), for unresectable
malignant melanoma and wishes to know more about this medication.
In October 2013, dabrafanib became the first PBS listed medication for the treatment of malignant
melanoma in patients with the BRAF V600 mutation. This mutation is present in approximately 50%
of all melanoma patients. It is highly efficacious in melanoma patients with BRAF V600E mutations,
with response rates of approximately 50% and progression-free survival of 6 months. There is also
early data to suggest that dabrafenib is effective in controlling metastases in the brain.
Which of the following side effects may require a dose reduction?
a.
b.
c.
d.
Hyperglycaemia
Pyrexia
Cutaneous Squamous Cell Carcinoma
All of the above
How certain are you?
1: not very; it’s a guess 2: moderately 3: very certain
The correct answer is b. Fever accompanied by severe rigors, dehydration, hypotension and/or acute
insufficiency occurred in clinical trials of dabrafenib. Patients should be counselled on this side effect
and should present to a medical professional if their temperature is greater than or equal to 38.5
degrees Celcius. In the case of severe non-infectious febrile events, dabrafenib should be restarted
at a reduced dose once fever resolves and as clinically appropriate.
Patient TJ has been informed that dabrafenib may affect pregnancy. Which of the following is true
for dabrafenib?
a. Dabrafenib potentially impairs spermatogenesis, which may be irreversible
b. Dabrafenib is pregnancy Category D and patients should be advised to avoid pregnancy.
c. Dabrafenib interacts with oral contraceptives and additional measures may be required to
prevent pregnancy.
d. All of the above
How certain are you?
1: not very; it’s a guess 2: moderately 3: very certain
The correct answer is d. Dafrafenib may impair male and female fertility. Male patients should be
informed of the potential risk for impaired spermatogenesis, which may be irreversible. With
reference to pregnancy, no adequately and well controlled studies have been conducted in pregnant
women taking dabrafenib. Dabrafenib is pregnancy Category D and should not be administered to
pregnant women unless the potential benefit to the mother outweighs the possible risk to the fetus.
If the patient becomes pregnant while taking dabrafenib, the patient should be informed of the
potential hazard to the fetus. Dabrafenib may result in decreased concentrations and the loss of
efficacy of hormonal contraceptives.
What are the recommended dosing instructions for dabrafenib?
a. Take TWO 75mg capsules TWICE a day at least 1 hour before or 2 hours after food
b. Take ONE 75mg capsule in the morning 30mins before food
c. Take ONE 75mg capsule TWICE a day with food
d. Take TWO 75mg capsules in the morning with food
How certain are you?
1: not very; it’s a guess 2: moderately 3: very certain
The correct answer is a. The recommended dose is 150mg (TWO 75mg capsules) TWICE a day.
Dabrafenib should be taken either at least 1 hour before, or at least 2 hours after a meal, leaving
approximately 12 hours between doses. It should be taken at similar times every day. If a dose is
missed, it should not be taken if it is less than 6 hours until the next dose.
Patient MB presents a prescription for Cycloblastin® (cyclophosphamide) to your pharmacy. There
are numerous indications for this medication and on questioning you ascertain that Miss MB has
multiple myeloma. Her doctor has prescribed three medications;
1. Cycloblastin® (cyclophosphamide) 500mg PO Day 1,8,15 and 22
2. Dexmethasone® (dexamethasone) 40mg PO Day 1 to 4 and 12 to 15
3. Revlimid® (lenalidomide) 25mg PO Day 1 to 21
Miss MB has been told to start this medication on MONDAY. Which of the following are the
appropriate directions and quantity for the cyclophosphamide?
a. Take ONE tablet at night on Days 1, 8, 15 and 22. Quantity supplied 4 tablets.
b. Take TEN tablets in the morning. Quantity supplied 50.
c. Take TEN tablets (500mg) once a week on a MONDAY. Take in the morning and drink plenty
of water. Quantity supplied 40 tablets.
d. Take ONE tablet (500mg) once a week on a MONDAY. Take in the morning and drink plenty
of water. Quantity supplied 40 tablets.
How certain are you?
1: not very; it’s a guess 2: moderately 3: very certain
The correct answer is c. Cyclophosphamide tablets are currently only available in 50mg strength,
therefore a 500mg dose requires 10 tablets. The patient has been told to start this medication on
MONDAY and the protocol indicates a once weekly dosing schedule (Day 1, 8, 15 and 22). Patients
should be well hydrated ( 2 to 3 litre of fluid per day) and be encouraged to void frequently during
cyclophosphamide treatment to prevent bladder irritation.EVIQ The SHPA Standards of Practice for
the Provision of Oral Chemotherapy for the Treatment of Cancer recommend pharmacists only
supply the quantity of tablets/capsules required for a cycle of treatment.SHPA Hence Mr MB should be
dispensed 40 tablets.
Revlimid® (lenalidomide) is an analogue of thalidomide which is used for the treatment multiple
myeloma. Like thalidomide, lenalidomide is Australian Pregnancy Category X and its use is
contraindicated in women of child-bearing potential who are not using adequate contraception.AMH
Which of the following recommendations would be appropriate for Miss MB?
a. Lenalidomide is not appropriate for Miss MB and she should discuss alternatives with her
doctor.
b. A combined oral contraceptive, such as Levlen®, should be started prior to treatment to
ensure effective contraception during treatment.
c. Ensure effective non-hormonal contraception during and for 1 month after treatment.
d. Barrier methods of contraception are ineffective at preventing lenalidomide-induced birth
defects.
How certain are you?
1: not very; it’s a guess 2: moderately 3: very certain
The correct answer is c. Lenalidomide is an appropriate treatment for Miss MB if she uses adequate
contraception. Due to the increased risk of thromboembolic events with lenalidomide, combined
oral contraceptive pills are not recommended. Non-hormonal contraceptive methods such as barrier
methods are recommended to prevent pregnancy during and for 1 month after lenalidomide
treatment.AMH To avoid embryo-fetal exposure patients are required to enrol and comply with
requirements of the Risk Evaluation and Mitigation Strategy (REMS) program. Details of the
REVLIMID REMSTA program are available at www.REVLAMIDREMS.com. Pharmacists need to be
certified in order to dispense lenalidomide.
Which of the following is not a reported side effect of lenalidomide?
a.
b.
c.
d.
Secondary malignancies
Photosensitivity
Fatigue
Neutropenia and thrombocytopenia
How certain are you?
1: not very; it’s a guess 2: moderately 3: very certain
The correct answer is b. Lenalidomide has been associated with an increased risk of secondary
malignancies, including solid tumours and non-melanoma skin cancers.AMH Fatigue is a commonly
reported side effect of lenalidomide.AMH Neutropenia and thrombocytopenia are common side
effects which are dose-limiting.AMH
Test your knowledge:
The incidence of endometrial changes is increased by which of the following medications?
a.
b.
c.
d.
Methoblastin® (methotrexate)
Revlimid® (lenalidomide)
Tarceva® (erlotinib)
Novadex-D® (tamoxifen)
How certain are you?
1: not very; it’s a guess 2: moderately 3: very certain
The correct answer is d.
Which of the following is an adverse effect of Xeloda® (capecitabine)?
a.
b.
c.
d.
Hypercalcaemia
Hand-foot syndrome
Interstitial lung disease
All of the above
How certain are you?
1: not very; it’s a guess 2: moderately 3: very certain
The correct answer is b.
Which of the following medications may require patients to follow a dosing schedule with planned
drug-free intervals?
a.
b.
c.
d.
Xeloda® (capecitabine)
Temodal® (temozolamide)
Sutent® (sunitinib)
All of the above
How certain are you?
1: not very; it’s a guess 2: moderately 3: very certain
The correct answer is d.
Panafcortelone® (prednisolone) is used in combination with abirterone to reduce which symptoms
associated with increased adrenal mineralcorticoid production?
a.
b.
c.
d.
Hypotension and peripheral oedema
Excess facial hair
Hyperlipidaemia
Immune dysfunction
How certain are you?
1: not very; it’s a guess 2: moderately 3: very certain
The correct answer is a.
Bactrim DS® (sulfamethoxazole/trimethoprim) is sometimes prescribed for patients taking oral
chemotherapy. Why?
a.
b.
c.
d.
To treat urinary tract infections
To treat dyspepsia
To prevent opportunistic infections
To prevent hand-foot syndrome
How certain are you?
1: not very; it’s a guess 2: moderately 3: very certain
The correct answer is c.
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