9/23/2011 Objectives 1. Identify patients at high risk for the following adverse effects: nausea and/or vomiting, mucositis, and peripheral neuropathy 2. Describe treatment options for chemotherapy induced nausea and vomiting based on the chemotherapy emetic Lindsey Dayer, Pharm.D. potential Assistant Professor 3. List 3 treatment options for management of UAMS College of Pharmacy chemotherapy induced peripheral neuropathy 4. Name 2 topical treatments and 1 oral treatment for management of targeted therapy induced rash 5. Identify 3 indications for initial treatment with vancomycin in patients with febrile neutropenia Technician Objectives I have nothing to disclose 1. Review common adverse effects associated with chemotherapy 2. Recognize agents used to treat chemotherapy induced nausea and vomiting, mucositis, peripheral neuropathy, rash, and febrile neutropenia 3. Compare and contrast the different agents used to treat chemotherapy induced nausea and vomiting Side effects of chemotherapy may lead to increased morbidity and mortality, increased cost of cancer care, and decreased quality of life. 1 9/23/2011 As the pharmacist, we can contribute by adding specific drug-related knowledge and offering patient-related services. Chemotherapy Induced Nausea and Vomiting (CINV) Pathophysiology of CINV There was a significant impact on patients’ daily functioning and quality of life in those who developed chemotherapy induced nausea and vomiting Types of CINV Risk Factors for Acute-Onset CINV Younger age (<50 y/o) Anticipatory Female Acute Poor control of symptoms in prior cycles Delayed History of motion sickness or nausea with Breakthrough pregnancy Refractory Anxiety/depression Absence of alcoholism 2 9/23/2011 High Emetic Risk Intravenous Chemotherapy Other Risk Factors for CINV Delayed-Onset CINV AC combination defined Dacarbazine Female as either doxorubicin or Doxorubicin > 60 mg/m² Poor control of symptoms in acute onset epirubicin with Epirubicin > 90 mg/m² cyclophosphamide Chemotherapy regimens with higher doses and Ifosfamide ≥ 10 g/m² faster infusion times Carmustine > 250 mg/m² Mechlorethamine Increasing number of cycles or chemotherapy Cisplatin ≥ 50 mg/m² Streptozocin regimens administered over several days Cyclophosphamide > Combination regimens 1,500 mg/m² Most predictive factor: chemotherapy agent’s tendency to cause CINV Moderate Emetic Risk IV Chemotherapy Low Emetic Risk IV Chemotherapy Aldesleukin > 12-15 million Dactinomycin Amifostine ≤ 300 mg Ixabepilone international units/m² Daunorubicin Aldesleukin ≤ 12 million Methotrexate > 50 mg/m² < 250 Amifostine > 300 mg/m² Doxorubicin ≤ 60 mg/m² international units/m² mg/m² Arsenic trioxide Epirubicin ≤ 90 mg/m² Cabazitaxel Mitomycin Azacitidine Idarubicin Cytarabine (low dose) 100-200 Mitoxantrone Bendamustine Ifosfamide < 10 g/m² mg/m² Paclitaxel Busulfan Interferon alfa ≥ 10 million Docetaxel Paclitaxel-albumin Carboplatin international units/m² Doxorubicin (liposomal) Pemetrexed Carmustine ≤ 250 mg/m² Irinotecan Eribulin Pentostatin Cisplatin < 50 mg/m² Melphalan Etoposide Pralatrexate Clofarabine Methotrexate ≥ 250 mg/m² 5-Fluorouracil Romidepsin Cyclophosphamide ≤ 1,500 Oxaliplatin Floxuridine Thiotepa mg/m² Temozolomide Gemcitabine Topotecan Cytarabine > 200 mg/m² Interferon alfa > 5 < 10 million international units/m² Moderate to High Emetic Risk Minimal Emetic Risk IV Chemotherapy Oral Chemotherapy Agents Alemtuzumab Ipilimumab Altretamine Asparaginase Methotrexate ≤ 50 mg/m² Bevacizumab Nelarabine Busulfan (≥ 4 mg/day) Bleomycin Ofatumumab Bortezomib Panitumumab Cyclophosphamide (≥ 100 mg/m²/day) Cetuximab Pegaspargase Estramustine Cladribine (2- Peginterferon chlorodeoxyadenosine) Rituximab Etoposide Cytarabine < 100 mg/m² Temsirolimus Lomustine (single day) Decitabine Trastuzumab Denileukin diftitox Valrubicin Procarbazine Dexrazoxane Vinblastine Fludarabine Vincristine Temozolomide (>75 mg/m²/day) Interferon alpha ≤ 5 million Vinorelbine international units/m² 3 9/23/2011 Minimal to Low Emetic Risk Emesis Prevention for IV Chemotherapy Oral Chemotherapy Agents High Emetic Moderate Low Emetic Minimal Risk Emetic Risk Risk Emetic Risk Bexarotene Melphalan Busulfan (< 4 mg/day) Mercaptopurine Day 1 5-HT3 Antagonist 5-HT3 Antagonist Dexamethasone No routine Capecitabine Methotrexate AND AND OR prophylaxis Chlorambucil Nilotinib Dexamethasone Dexamethasone Metoclopramide Cyclophosphamide (< 100 Pazopanib AND AND OR mg/m²/day) Sorafenib Neurokinin 1 (Neurokinin 1 Prochlorperazine Dasatinib Sunitinib Antagonist Antagonist) (start prior to Erlotinib Temozolomide (≤ 75 mg/m²/day) chemo) Everolimus Thalidomide Days 2-3(4) Dexamethasone 5-HT3 Antagonist Fludarabine Thioguanine (days 2-4) AND (days 2-3) OR Geftinib Topotecan Neurokinin 1 Dexamethasone Hydroxyurea Tretinoin Antagonist (days (days 2-3) OR 2-3) (Neurokinin 1 Imatinib Vandetanib Lapatinib Antagonist) Vorinostat Lenalidomide Breakthrough Lorazepam, dronabinol, haloperidol, metoclopramide, olanzapine, scopolamine, Medications prochlorperazine, promethazine, 5-HT3 antagonists, dexamethasone Prevention of Anticipatory Nausea and Emesis Prevention for Oral Chemotherapy Vomiting Start before chemotherapy and continue daily Use optimal antiemetic therapy during every cycle of treatment High to moderate emetic risk PO granisetron or PO ondansetron Behavioral therapy Low to minimal emetic risk Recommend PRN initially, then if not Relaxation/systemic desensitization controlled, may switch to: Hypnosis/guided imagery Metoclopramide 10-40 mg PO, then every 4-6 h PRN Music therapy OR Acupuncture/acupressure Prochlorperazine 10 mg PO, then every 4-6 h PRN Lorazepam PO the night before and morning of OR treatment OR alprazolam PO TID beginning on the Haloperidol 1-2 mg PO every 4-6 h PRN If continued N/V, recommend PO night before treatment 5-HT3 antagonists Treatment of Breakthrough Nausea and Vomiting Nausea and Vomiting Prevention Conduct a careful re-evaluation of emetic risk, disease Patient education status, concurrent illnesses, and medications Prevention Prevention Prevention Clarify that the best regimen is being administered Stress to the patient importance of taking antiemetics Give an additional agent from a different drug class PRN Encourage patient to “use” prn medication If controlled, continue breakthrough medications on a Life-style modifications schedule, not PRN If not controlled, consider changing to higher-level primary treatment 4 9/23/2011 Dietary Approaches to Manage Nausea Dietary Approaches to Manage Vomiting Eat foods that are easy on your stomach Prevent nausea Eat 5 or 6 small meals each day Wait for vomiting to stop before eating or drinking Do not skip meals and snacks Once the vomiting stops, drink small amounts of clear Choose foods that appeal to you liquids Sip only small amounts of liquids during meals Once you can drink clear liquids without vomiting, try Eat dry toast or crackers before getting out of bed if full-liquid foods and drinks you have nausea in the morning Eat more small meals instead of less larger meals Plan when it is best for you to eat and drink Case #1 AB is a 49 year old male recently diagnosed with head and neck cancer. He will begin treatment today with Cisplatin 100 mg/m2 every 3 weeks for 3 doses. Which antiemetic regimen should AB receive prior to chemotherapy? a. Ondansetron + Dexamethasone + aprepitant b. Ondansetron + Dexamethasone + prochlorperazine for breakthrough c. Dexamethasone + prochlorperazine for break through d. Ondansetron + Dexamethasone Mucositis 5 9/23/2011 Pathophysiology of Mucositis Pathophysiology of Mucositis Epithelial lining of the GI tract turns over every 7-14 Usually progresses in a stepwise fashion days Asymptomatic redness/erythema occurring 0-5 days Ranges from mild inflammation to bleeding after therapy ulcerations Desquamation with white patches occurring 0-7 days Affects non-keratinized oral mucosa (labial, buccal after therapy and soft-palate mucosa, floor of the mouth, ventral Contiguous pseudomembranes occurring 6-12 days after aspect of the tongue) therapy Painful lesions with or without ulceration occurring 12- 16 days after therapy Lalla et al. Oral Toxicity. The Chemotherapy Source Anthony et al. Support Care Cancer. 2006; 14: 56-8 Book. 4th Edition. 2008: 115-35 WHO Grading System for Mucositis Chemotherapy-Induced Mucositis Grade 0: None 40-75% will experience mucositis Grade 1: Soreness +/- redness, no ulceration 70-80% undergoing bone marrow transplantation with Grade 2: Redness, ulcers. Patients can swallow solid radiation-based condition regimens will develop diet mucositis Grade 3: Ulcers, extensive redness. Patients cannot Course parallels neutrophil nadir swallow solid diet Continuous infusions cause more mucositis than short Grade 4: Oral mucositis to the extent that eating is not IV infusions possible Chemotherapy combined with radiation leads to worse mucositis than either given alone Scully et al. Head & Neck. 2003; 25: 1057-70 Risk Factors for Mucositis Outcomes of Mucositis Pre-existing oral lesions Mucositis can lead to: Poor dental hygiene or ill-fitting dentures Delaying subsequent chemotherapy cycles Combined modality treatment with chemotherapy Dosage reductions plus radiation Discontinuation of chemotherapy regimens Ethnicity (Caucasians > African Americans) Feeding tubes Development of fever