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Kristi Hofer, B.Sc.Pharm October 29, 2013 1. Identify the class/category of and mechanism of action of common oral anti-cancer agents. 2. Identify the types of cancers that these agents are used in, and provide examples of drug names. 3. Recognize educate patients on common side effects of oral anti-cancer therapies. 4. Understand safe handling of oral anti-cancer agents in the pharmacy as well as in the home. 5. Identify strategies for promoting safety in prescribing, educating and monitoring oral anti-cancer therapies No conflicts of interest to disclose 3 Way of the future ◦ About 45% of new cancer drugs in Phase 2/3 trials are oral ◦ Preferred choice of provider & patient ◦ Universal: used in all types and stages of cancer Unique challenges ◦ Lack of formal guidelines & education materials ◦ Informing & monitoring patients ◦ Shift of responsibility to patient and families Barton, 2011;Birner, 2003; Moody & Jakowski 2010; NCCN, 2008; Winkljohn ,2007 80+% of patients prefer oral chemotherapy, but only provided this is not at the expense of efficacy ◦ given at home (cited by 57% of patients) ◦ avoidance of venepunctures (55%) ◦ greater sense of ‘control’ over their treatment (33%) O’Neill, VJ., Twelves, CJ.,2002 5 Patient convenience / preference Flexibility in dosing and scheduling Prolonging drug exposure Decreased resource utilization Altered toxicities Improved quality of life 6 Studies show that both patients and health care providers underestimate the impact on safety and patient tolerance ◦ ◦ ◦ ◦ ◦ Drug-Drug Interactions Drug Food Interactions Adherence Patient Monitoring Cost CANO position statement 2013 7 “Anti-Cancer” treatments include: ◦ ◦ ◦ ◦ Cytotoxic agents Hormonal agents Immunotherapies Targeted Therapies “Supportive Care” medications include: ◦ ◦ ◦ ◦ ◦ ◦ Anti-emetics Colony stimulating factors (g-csf; filgrastim) Bisphosphonates Antihistamines Anticoagulants Steroids 8 Neo-adjuvant: Shrink tumour before surgery Adjuvant: Cancer is removed by surgery. Reduce chance of cancer coming back (relapse) Metastatic: Shrink or control cancer growth to improve quality of life (palliative) 9 Treatment plans are called regimens: ◦ combination of cancer meds (oral and IV) plus supportive care meds Treatment Cycles ◦ ◦ ◦ ◦ ◦ time period in between regimens counted in days Most cycles are 14, 21 or 28 days long Treatment day = day 1 May have multi-day treatments, such as day 1, 8, 15 OR day 1, 2, 3 10 May include oral cancer meds, IV cancer meds or both. May include radiation therapy ◦ Radiation may be given before, after or during systemic therapy 11 Mechanisms of Action Adverse Effects Examples 12 Hormonal therapy: ◦ interferes with the production or action of specific hormones and causes the cancer to stop or slow its growth. ◦ Usually have less severe side effects. ◦ Side Effects include: hot flashes, nausea, fatigue, increased lipids, bone loss ◦ Anti-estrogens, anti-androgens Examples: anastrazole, letrozole, medroxyprogesterone, tamoxifen, bicalutamide, abiraterone, enzalutamide 13 Immunotherapy: ◦ alter the body’s response to the tumour, or ◦ stimulate the immune system to fight the cancer ◦ may be a compound that is already produced in the body, but given in much larger quantities than a human body produces. ◦ Side effects include: nausea, headache, myelosupression, liver dysfunction (dose limiting), fatigue, depression Example: Interferon alpha-2b (Intron A) 14 Targeted Therapies ◦ newer agents that have been designed to bind to extracellular targets on cancer cells. ◦ Often less toxic because they don’t kill healthy cells. ◦ Associated with unique side effects that are not traditionally associated with chemotherapy. 15 Cytotoxic agents: ◦ interfere with DNA or RNA processes and prevent cell replication and function. ◦ non-specific action; also kill healthy cells. ◦ associated with significant side effects such as nausea, vomiting, diarrhea, alopecia, myelosupression 16 17 Cell Phase Specific Non-Cell Phase Specific 18 Toxic to proportion of cells in the phase that the agent is active in Ideally given as a “continuous infusion” (oral dosing or frequent dosing) Kill proliferating cells (schedule dependant) Pyrimidine antagonists Antifolates Purine analogues 19 Inhibit thymidylate synthase Capecitabine: ◦ a pro-drug selectively activated by tumor cells ◦ undergoes a 3-step conversion to 5-FU, the last step being phosphorylation by thymidine phosphorylase (TP). ◦ TP levels are higher in tumor cells than normal tissues, therefore the systemic exposure of active drug is minimized. Side effects: diarrhea, hand-foot syndrome, rash, nausea/vomiting, 20 Inhibits dihydrofolate reductase Methotrexate ◦ Used in childhood leukemias ◦ Once weekly dosing Side effects: nausea/vomiting, rash, photosensitivity, alopecia, myelosuppression, increased LFTs 21 Resembles guanine and is incorporated into DNA Mercaptopurine/Thioguanine ◦ Hepatotoxicity, stomatitis, myelosupression Fludarabine – unique immune supression of thelper cells ◦ require prophylactic antibiotics ◦ Opportunistic infections, viral reactivation 22 Exert effect throughout entire cell cycle Kill is proportional to dose (not schedule) Alkylating Agents: prodrugs which form covalent bonds with DNA and break the DNA strand ◦ Nitrogen Mustards ◦ Nitrosoureas ◦ Triazenes 23 Cyclophosphamide ◦ Dose limiting toxicity is myelosupression ◦ Nausea/vomiting, alopecia, infertility, secondary leukemias, hemorrhagic cystitis Counselling: ◦ Take in the morning ◦ Drink 3 L fluid/day ◦ Void frequently (q2h) Used in lymphoma, breast ca, small cell lung ca 24 Chlorambucil ◦ SE: immunosupression, anorexia Used in: CLL (chronic lymphocytic leukemia), lymphomas 25 Lomustine ◦ Nausea/vomiting, pulmonary toxicity, ◦ Delayed myelosupression (nadir at 4 weeks) ◦ Q 6 week dosing Counselling: ◦ Empty stomach Used in brain tumours 26 Temolozomide ◦ Crosses blood brain barrier ◦ SE: Nausea/vomiting, increased LFTs, myelosupression Used in brain tumours, melanoma 27 Most cause myelosupression ◦ May be dose limiting ◦ May require rest period in between cycles ◦ Fever/infection is an emergency- recommend immediate assessment Changes in liver or kidney function, as well as thrombocytopenia, neutropenia, anemia can occur ◦ Frequent bloodwork required ◦ Dose adjustments Not all cause alopecia or nausea/vomiting Therapy that is directed at a specific target on the cell that controls or signals cancer growth, proliferation and angiogenesis Targets are often over-expressed in cancer cells (less effect on normal cells) Main targets: ◦ Cell surface markers (e.g. CD20) ◦ EGFR-epidermal growth factor receptor ◦ VEGF- vascular endothelial growth factor Unique side effects: skin rashes, diarrhea, hypertension, photosensitivity 29 30 Monoclonal Antibodies (IV) Tyrosine Kinase Inhibitors Miscellaneous Agents 31 Erlotinib and Gefitinib: ◦ inhibit the intracellular phosphorylation of several tyrosine kinases associated with transmembrane cell surface receptors ◦ epidermal growth factor receptor tyrosine kinase (EGFR-TK) is overexpressed on the cell surface of 50-80% of NSCLC. ◦ Inhibition decreases the growth, invasion, metastasis, angiogenesis, and resistance to apoptosis Side effects: diarrhea, rash (“acne-like”), dry skin, nausea/vomiting 32 Erolitinib/Gefitinib cont’d Counselling: ◦ Rash may be indicative of efficacy ◦ Do not use acne products ◦ Use moisturizers, sun screen, topical steroids Drug interactions, including warfarin Used for: lung cancer (2nd and 3rd line), pancreatic cancer 33 Lapatinib: ◦ Tyrosine kinase inhibitor of EGFR and Her-2. Side effects: diarrhea, cardiac toxicity, rash, hand and food syndrome Used in: metastatic breast cancer (with capecitabine) 34 Sorafenib and Sunitinib ◦ inhibitor of multiple receptor tyrosine kinases (plateletderived growth factor receptors, vascular endothelial growth factor receptors, stem cell factor receptor) Side effects: diarrhea, dyspepsia, stomatitis, handand- foot syndrome, rash, hypertension Used in: advanced renal cell carcinoma 35 Everolimus: ◦ mTOR inhibitors ◦ Mammalian target of rapamycin (mTOR) is a intermediary signalling pathway which signals other events in the cell cycle that control growth and angiogenesis Side effects: rash, asthenia, mucositis, nausea, edema, anemia, hyperglycemia, hyperlipidemia, hypertriglyceridemia Used in: metastatic renal cell carcinoma 36 Vemurafenib ◦ Inhibits MAP kinase signaling pathway through inhibition of ATP binding to mutated BRAF preventing phosphorylation and activation of downstream pathways Side effects: arthralgia, rash, alopecia, fatigue, photosensitivity reaction, nausea, pruritus, and skin papilloma. Used in: metastatic melanoma (with BRAF mutation) 37 Thalidomide and Lenalidomide ◦ Immunomodulator ◦ MOA not fully known Dispensed through RevAid programs Side effects: somnolence, dizziness, constipation, hypotension, rash, increased chance of blood clots 38 Unique side effects may require special considerations ◦ Immune modulated diarrhea requires high dose steroids ◦ Rashes may be indicative of efficacy ◦ Rashes should be treated according to protocols; avoid products that dry the skin ◦ Severe sun sensitivity ◦ May affect lipids, blood pressure, blood sugar and require meds to treat Anna is a 58 year old woman who was diagnosed with HER-2 positive breast cancer. She had a right lumpectomy and started adjuvant chemotherapy followed by radiotherapy. Because her cancer type is hormonesensitive, she takes an aromatase inhibitor. Anna is a retired lawyer and lives with her 65 year old husband, who is also a lawyer and is in good health. She looks after her 4 year old granddaughter on weekdays from 8 am to 6 pm. She takes no other medications, apart from a mild painkiller occasionally for headaches. Anna had been receiving adjuvant trastuzumab when she came in for a follow-up visit and was found to have liver metastasis. After taking into account Anna’s preference to receive oral therapy, her oncologist, prescribed the combination of two oral agents: capecitabine and lapatinib.The new treatment plan is for Anna to receive 2000 mg/m2 of capecitabine, so she needs to take four 500 mg pills in the morning and three 500 mg pills in the evening for 14 days on a 3 week cycle. She is also to take 5 lapatinib pills daily, and to stop taking the aromatase inhibitor pills. In total, Anna has to take 12 pills per day on her treatment days. Lacks built-in safeguards and processes ◦ Multiple checks and established process for IV treatment ◦ Multiple opportunities to educate when on IV ◦ Physician can hand Rx directly to patient Dispensing in Manitoba ◦ Most oral agents dispensed in community pharmacies ◦ Community pharmacist does not have access to pertinent information such as height, weight, bloodwork, treatment plan/goal ◦ Community pharmacist may assume complete education provided at CCMB 41 Shift in responsibility to patients and families ◦ Correctly administer ◦ Monitor and manage side effects ◦ Identify side effects vs symptoms of cancer Complicated regimens ◦ May be chronic or cyclical ◦ Complexity of dosing schedule ◦ May be used in combination with IV or other oral medications 42 Common misconception that oral treatments are safer than IV ◦ Less rigorous checking processes, communication plans, patient education Poor adherence ◦ Seems less serious if treatments are oral ◦ Complicated regimens ◦ Chronic side effects 43 Twice Before Starting (Clinic visit + phone call or 2nd visit) • Know why taking oral chemo • Know how to take • Know what to expect 10 to 14 Days after • Assess educational needs • Assess tolerance starting • Assess ability to adhere chemotherapy Before Repeat Prescriptions (next cycle or 4-6 weeks) D O C U M E N T • Assessment • Lab work • Nurse/physician 44 Twice Before Starting (Clinic visit + phone call or 2nd visit) • Know why taking oral chemo • Know how to take • Know what to expect Rationale for 2 encounters o Information overload at initial visit o Learning needs reinforcement D O C U M E N T o Instructions reviewed for clarity once filled o Assess need for compliance aids 45 Clear, specific directions ◦ ◦ ◦ ◦ ◦ When and how to take medications Number of pills not known in clinic Calendars? Diaries? Recognizing and managing potential side-effects Triggers for contacting clinic staff Reinforce with written materials ◦ Drug-specific information sheets ◦ Safe-handling information Multinational Association of Supportive Care in Cancer (www.mascc.org) MOATT guides you through all aspects of the education process Available in 12 languages 47 4 Key Elements: 1. Key assessment questions 2. Generic education discussion points 3. Drug specific education 4. Evaluation questions to help ensure patient understanding 48 KEY ASSESSMENT QUESTIONS 1) What have you been told about this treatment plan with oral medications? * Verify that the patient knows that these oral agents are for cancer and are taken by mouth for their cancer. 2) What other medications or pills do you take by mouth? * If you have a list of medicines, go over the list with the patient. * If you do not have a list, ask the patient what medicines he/she is taking, (both prescription and non-prescription), herbs, complementary, or other treatments. MASCC TEACHING TOOL FOR PATIENTS RECEIVING ORAL AGENTS FOR CANCER (MOATT)© 3) Are you able to swallow pills or tablets? If no, explain. 4) Are you able to read the drug label/information? 5) Are you able to open your other medicine bottles or packages? 6) Have you taken other pills for your cancer? This teaching tool has been prepared to assist health care providers in the assessment and education of patients receiving oral agents as treatment for their cancer. The goal is to ensure that patients know and understand their treatment and the importance of taking the pills/tablets that are prescribed. * Find out if there were any problems, for example, taking the medications or any adverse drug effects. 7) Are you experiencing any symptoms that would affect your ability to keep down the pills, for example nausea or vomiting? 8) How will you fill your prescription? * Delays in obtaining the pills may affect when the oral drugs are started The following are aspects that impact the 9) Have you had any problems with your insurance that has interfered with obtaining your medications? adherence to treatment with oral agents (pills/tablets) for cancer Patient Characteristics Drug Disease Treatment Plan Special Considerations when assessing patients receiving oral agents for cancer: When teaching the patient, you may need to adapt your teaching to accommodate special considerations such as, age, feeding tube, vision problems/color blindness, dietary issues, mental problems (dementia, depression, cognitive impairments). Include family member or other healthcare provider in this information. * Recommended information to assess is noted in italics © 2008 Multinational Association of Supportive Care in Cancer PATIENT EDUCATION Generic Education for All Oral Drugs Discuss the following items with the patient and/or caretaker. 1) Inform any other doctors, dentists or healthcare providers that you are taking pills/tablets for your cancer. 2) Keep the pills/tablets away from children and pets and in a childproof container. 3) Keep the pills/tablets in the original container, unless otherwise directed. It could be dangerous to mix with other pills. 4) Wash your hands before and after handling the pills/tablets. 5) Do not crush, chew, cut or disrupt your pills/tablets unless directed otherwise 6) Store your pills/tablets away from heat, sunlight, or moisture as it may degrade the pills/tablets, potentially making them less effective. 7) Have a system to make sure you take your pills/tablets correctly. * Give the patient some ideas, such as timer, clock or calendar. 8) Make sure you have directions about what to do if you miss a dose 9) If you accidentally take too many pills or if someone else takes your pills/tablets, contact your Doctor or nurse immediately. 10) Ask your nurse or pharmacist what you should do with any pills/tablets you have not taken or are out-dated. * The patient may be asked to bring unused pills/tablets back to the next visit. 11) Carry with you a list of medicines that you are taking, including your cancer pills/tablets. 12) Let us know if you have a problem with paying for or getting your pills. 13) Plan ahead for travel, refills and weekends. TM 49 DRUG-SPECIFIC INFORMATION Drug name (generic and trade) __________________________________________ What the drug looks like __________________________________________ EVALUATE Have the patient and/or caregiver answer the following questions to ensure that they understand what information you have given them. Dose and schedule How many different pills? __________________________________ You have received a lot of information today. Let’s review key points. How many times a day? ___________________________________ What is/are the name(s) of your cancer pill(s)/tablet(s)? For how long? __________________________________________ Where the drug should be stored * Be specific, for example, away from heat (not in the kitchen), humidity (not in the bathroom), sun (not on the window sill) __________________________________________ __________________________________________ What are potential side effects and management of them? * Include lab evaluations or any medical tests that will be used for drug monitoring. __________________________________________ __________________________________________ __________________________________________ __________________________________________ Are there any precautions? __________________________________________ __________________________________________ __________________________________________ Are there any drug and food interactions? __________________________________________ __________________________________________ When and whom to call with questions * Give names and phone numbers here __________________________________________ __________________________________________ When will you take your cancer pill(s)/tablet(s)? Does it matter if you take this pill/tablet with food or not? Where do you plan to keep it? When should you call the Doctor or Nurse? Do you have any other questions? Your next appointment is? ______________________________________ For problems, contact ______________________________________ ______________________________________ ______________________________________ ______________________________________ ______________________________________ Drug-Specific Education – The following information relates to topics and references for the specific treatment that the patient is receiving. Refer to drug specific information to educate the patient on his/her pills/tablets References Product package insert or prescribing information http://www.cancerbackup.org.uk/Treatments/Ch emotherapy/Individualdrugs Micromedix AHFS Drug Info. http://www.cancersource.com/LibraryAndResou rces/DrugGuide/ http://www.naturaldatabase.com Add website addresses, email links, internet sites Whichever tool is used to educate the patient, include the following drug-specific information. You can complete the form provided below and give it to the patients using reference material you have on the specific pills/tablets. Drug name (generic and trade) What the drug looks like Dose and schedule. How many different pills? How many times a day? For how long? Where to store the drug * Be specific, for example, away from heat (not in the kitchen), humidity (not in the bathroom), sun (not on the window sill) What are potential side effects and management of them? * Include lab evaluations or any medical tests that will be used for drug monitoring. Are there any precautions? Are there any drug and food interactions? When and whom to call with questions * Give names and phone numbers here 50 10 to 14 Days after • Assess educational needs • Assess tolerance starting • Assess ability to adhere chemotherapy o Pre-plan encounter (e.g. schedule phone call) o Focus on more than just side effects o How is life being affected? o Referrals needed? D O C U M E N T 51 Before Repeat Prescriptions • Assessment (next cycle or 4-6 weeks) • Lab work • Nurse/physician o Physician and/or specialized oncology nurse o Toxicities and side effect management o Required lab and imaging D O C U M E N T o Adherence assessment o Medication reconciliation 52 World Health Organization definition of adherence: “The extent to which a person’s behaviour corresponds with agreed recommendations from a health care professional” Ability to follow timing, dosage, frequency Persistence –ability to maintain behaviours over time 53 Provider & Treatment-Related Patient & Disease-Related Literacy level Language Motivation Social support Belief in efficacy of regimen Mental and physical health Self- efficacy Understanding goals of treatment Complexity of regimen Clarity of instructions Degree of behavior change needed Relationship with health care providers Degree of concordance among members of health care team Availability of team to respond to symptoms Elliot, 2008; Hartigan, 2003;; Marin & Baxeos, 2010; Verhoef et.al, 2009; Winklejohn, 2oo7 54 Dexamethasone: days 1,2, 3 4, 9, 10, 11,12,17,18, 19, 20 of a 28 day cycle Hydroxyurea 500 mg twice daily on Mon, Wed, Fri, and three times daily on Tue, Thu, Sat, Sun. Temozolomide (ondansetron 30 min pre) once daily days 1-21 and celecoxib twice daily days 1-28 of a 28 day cycle. Plus Septra DS once daily Mon, Wed, Fri. 55 Explain significance of adherence ◦ Essential to efficacy + evaluating efficacy Consider provider assumptions ◦ Cancer a motivator? ◦ Taking as prescribed? Encourage successful self-administration Contact: regular and ongoing Tools: Calendars, alarms, diaries, blister packs Phone calls 56 Pharmacists working together ◦ Communicate treatment plans ◦ Suggest strategies to improve adherence ◦ Don’t assume patient has received adequate education at CCMB ◦ Electronic prescription vs. hand-written ◦ Blister pack chemo drugs separately to promote adherence and allow for dose modifications 57 Electronic Rx No abbreviations Include parameters used to calculate dose No refills! 1 cycle or 4 to 6 weeks ◦ Ensures proper assessment of patient including relevant bloodwork ◦ Prevents toxicity (e.g. week off in between cycles) ◦ Enables repeated evaluation of adherence ◦ Prevents errors when dose adjustments are made All staff who may come in to contact with oral cytotoxic agents should have appropriate training ◦ Attend training specific to their roles ◦ Safe handling of hazardous drugs ◦ Written plan for spill or accidental exposure Store hazardous drugs separately from other drugs ◦ Consider manufacturer specifications eg: protect from light Goodin 2011 Wear disposable gloves when dispensing ◦ Wash hands before and after glove application Use separate equipment for dispensing ◦ Use disposable materials if possible ◦ Wash equipment after use Do not use automatic dispensing machines Compounding, splitting, crushing should be done in BSC wearing personal protective equipment Goodin 2011 Patients and their caregivers need to be educated about safe-handling of chemotherapy medications at home ◦ Safe handling of medication ◦ Safe handling of body wastes 61 Wear gloves when handling tablets or capsules (caregiver) ◦ Wash hands after removing gloves Do not split or crush cancer medications Tell your pharmacist if you cannot swallow the drugs whole Store drugs in a secure place away from heat & moisture Store drugs out of reach of children and pets Take unused medications to a pharmacy 62 Body waste is contaminated for about 48 hours after the last dose of cytotoxic medication is taken (IV or oral) Wear gloves when cleaning up waste Wash soiled clothes or linens separately Wash hands well Close toilet lid and flush twice 63 If a spill occurs: ◦ Use spill kit if provided ◦ Wear gloves when cleaning up ◦ Wash surfaces twice All patients with home infusions of IV chemotherapy receive a home spill kit. 64 Oral chemo is “huge” now and in the future Presents unique challenges Depends on successful self-administration including monitoring and some self-management of side-effects Education essential– multidisciplinary, intentional includes the patient 65 BC Cancer Agency drug monographs (www.bccancer.bc.ca) CANO position statements 2013 ((http://www.cano-acio.ca) Given, B., Spoelstra, S. & Grant, M. (2011). The challenges of oral agents as antineoplastic treatments. Seminars in Oncology Nursing, 27, (2), 93-103. Goodin S, Griffith N, Chen, B et al (2011). Safe Handling of Oral Chemotherapeutic Agents in Clinical Practice: Reccomendations from an International Pharmacy Panel. Journal of Oncology Practice, 7 (1), 7-12 MASCC tool for patient adherence: http://data.memberclicks.com/site/mascc/MOATT_English_2010.pdf O’Neill, VJ., Twelves, CJ., British Journal of Cancer, (2002) REVIEW: Oral Cancer Treatment: developments in chemotherapy and beyond, 933-937 Spoelstra, S., Given, B. Given, C. & Grant, M. (2011). Policy Implications of Oral Agents. Seminars in Oncology Nursing, 27, (2) 161-165 Weingart SN, Brown E, Bach PB et al.(2008) NCCN Task Force Report: Oral Chemotherapy. Journal of the National Comprehensive Cancer Network, 6 (suppl 3), S-1-14 Winklejohn, D.L. (2007). Oral chemotherapy medications: the need for a nurse’s touch. Clinical Journal of Oncology Nursing, 11(6), 793-796 67