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. Certificate of Completion: Reference List: