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Session #3 Mfoflox-6 FOLFIRI ± Bevacizumab

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Session #3 Mfoflox-6 FOLFIRI ± Bevacizumab Management of Patients Receiving Oral Chemotherapy Siu Fun Wong, PharmD, FASHP, FCSHP Professor and Associate Dean Chapman University School of Pharmacy (CUSP) Irvine, CA Disclosure I have no conflict of interest . Objectives At the end of the presentation, the participants will be able to: 1. Recognize the difference in care required by patients receiving parenteral vs. oral chemotherapy 2. Deliver personalized care to patients receiving oral chemotherapy 3. Provide appropriate education relating to oral chemotherapy to patients and/or caregivers. Types of Oral Anti-cancer Chemotherapy Cytotoxic Agents Hormone Agents Immunomodulators Differentiating Agents Targeted Therapy Paradigm Change The rise in the use of oral oncology drugs represents a major shift in the management of patient . Directly observed treatment to unsupervised self- administration setting . Intermittent to daily chronic therapy . Perception of less toxicity with oral route of administration – both patients and providers1 . Patient preference due to convenience without compromise for efficacy2 . Provider preference, especially in palliative or adjuvant setting where QOL is paramount3 1Sharma S & Saltz LB. The Oncologist 2000; 5:99-107 2 Liu G et al. J Clin Oncol1997; 15(1):110-115 3 Benjamin et al. Eur J Cancer 2012;48(6):912-920 Goal How to empower patients to take the right dose at the right time under the right circumstances and to complete the treatment !! Effective Use and Monitoring Key (Unique) Elements to Consider Drug Administration Drug Interactions – Pharmacogenomics or genetic effect Adverse reaction management Adherence Safe handling Special Considerations for Oral Administration • Drug administration tolerability • Pharmacokinetics : Absorption, distribution, metabolism, excretion – Drug formulation, GI functions, drug interactions • Dosing regimen/scheduling • Specific patient considerations – safe handling Mechanisms of Drug Interactions Where? Pharmacokinetic: Absorption, Distributions, Metabolism, Excretion Pharmacodynamic: change in the patient’s response to a drug without altering the PK of the object drug How? – Formulation incompatibility – Drug binding – Drug transporters – Protein binding – Receptor binding – Enzyme activities (lifestyle) – Genetic variations – Drug-disease interactions Clinical Drug Interactions - Absorption Oral Chemo Interactions/Mechanis Management m Afatinib, chlorambucil, Food - bioavailability Empty stomach melphalen, 6-MP, (reduced AUC) capecitabine, temozolamide, sorafenib Vorinostat, regorafenib, Food - AUC Check study admin bosutinib, cabozantinib, condition to erlotinib, nilotinib, lapatinib, determine +/- food pazopanib, t-RA Estramustine Calcium-rich food – 1 hr before or 2 hrs impair absorption after Axitinib, bosutinib, crizotinib, pH-dependent solubility Separate antacids, dasatinib, nilotinib, erlotinib, – decrease AUC & H2 blockers, ponatinib, vismodegib avoid PPI Methotrexate, vismodegib, Dose-related saturation Separate daily tamoxifen PK dose Topotecan, vismodegib P-gp inhibitor – increase Avoid concurrent bioavailability administration Pharmacogenomic Effect Drugs Conditions or Biomarkers Clinical Effect Capecitabine Dihydropyrimidine ↑ toxicity dehydrogenase (DPD) deficiency (DPYD*2A) Crizotinib EML4-ALK fusion oncogene + Efficacy for crizotinib, ? ↓ erlotinib efficacy Everolimus Lapp lactase deficiency Diarrhea, malabsorption Erlotinib Epidermal Growth Factor ↑ treatment Receptor (EGFR) mutation+ response Kras mutation+ Poor response 6-MP Thiopurine methyltransferase ↑ myelo- (TPMP) deficiency suppression Tamoxifen CYP2D6*3 or *4 poor ↓ efficacy metabolizer Side Effects of Oral Anti-cancer Agents • Hematologic Complications • Dermatologic toxicities • Neurologic • Ophthalmic • Cardiologic • Pulmonary • Gastrointestinal • Fluid retention • Lab Abnormalities/renal Hematologic Complications • Myelosuppression -Neutropenia, anemia, thrombocytopenia • Cytotoxic agents, bosutinib, pazopanib • Hemorrhage - Bleeding, epistaxis • Bleeding: Cytotoxic agents, regorafenib, vandetanib, vorinostat (esp used w valproic acid) • Epistaxis: afatinib, cabozantinib • Thromboembolic events - PE, DVT • Tamoxifen, thalidomide, vorinostat • INR changes – concurrent use with warfarin • Erlotinib, nilotinib, sorafenib, vorinostat, Hematologic Complications Patient Management • Assess pt risks • Education for precautions • Neutropenia, anemia, thromobocytopenia • s/sx of conditions and potential complications • s/sx of DVT & PE • Prophylactic interventions • Laboratory monitoring • Supportive care Dermatologic Toxicities • Hand-Foot Syndrome • Skin/Nail Reactions – Hypersensitivity reaction –maculopapular rash – Photosensitivity – Dermatitis – Papulopustular rash – Paronychia – Pigmentation changes – Radiation Recall Hand-Foot Syndrome • aka palmar-plantar erythrodysesthesia • Agents: • Capecitabine, axitinib, cabozantinib, lapatinib, regorafenib, sorafenib, sunitinib • Onset can be from 2 to 12 days after initiation of therapy • May progress 3 to 4 days later into symmetrical edema and erythema of the palms and soles Hand –Foot Syndrome Grading Hand –Foot Syndrome Management • Systemic Agents – Pyridoxine or vitamin B6 – Dexamethasone – Amifostine – COX-2 inhibitors • Topical agents – Bag Balm, a topical petroleum-lanolin-based ointment with the antiseptic ingredient hydroxyquinoline sulfate. – Emollients, e.g. Biafine, Carmol 40 – Aloe vera lotion – Moisturizing creams. • Non-pharmacologic Interventions – Avoid undue pressure or rubbing of the skin – Avoid blood vessel dilation induced by hot showers or sun exposure – Cooling with cold water Ann Oncol. 2007;18:1159-1164. Skin/Nail Reactions • Hypersensitivity reaction –maculopapular rash • Photosensitivity • Dermatitis • Papulopustular rash • Paronychia • Pigmentation changes • Radiation Recall Dermatitis • Capecitabine, axitinib, bosutinib, regorafenib, vandetanib • s/sx: Generalized skin rash +/- pruritis • Can be worsen by sun exposure • Use products with SPF > 30 • Apply 30-60 mins before sun exposure and reapply every 2 hours • Moisturizer • Dose reduction may help EGFRI-Induced Dermatologic Toxicity Paronychia Papulopustular Rash Trichomegaly EGFR Inhibitor – Induced Dermatologic Toxicity • Erlotinib, afatinib, everolimus, vandetanib • Dermatologic toxicities include: – Papulopustular (Interfollicular and follicular-based erythematous papules and pustules) rash, xerosis, paronychial inflammation • Papulopustular Rash: – Onset: 1-2 weeks – Usually occur on face, scalp, and upper body – Symptoms: dry skin, pain/tenderness and pruritus – Inflammatory and infectious sequelae • Papulopustular Rash is common – 35-88% (all grades) – 16% (grade 3 or 4) – Dose reduction or discontinuation are recommended • Potential marker for drug activity and clinical outcome Pigmentation Changes • Skin • Hyperpigmentation – busulfan, 6-MP • Skin discoloration (yellow) - sunitinib • Hair • Hair color change • Cabozantinib, panzopanib, sunitinib Neurologic Toxicities • Seizure – hi dose busulfan, chlorambucil, vandetanib (RPLS – seizure, HA, visual disturbance, mental status changes) • Muscle spasm – vismodegib, vorinostat • Drowsiness, somnolence, tremor, peripheral neuropathy - thalodimide • Headache, dizziness – t-RA Ophthalmic • Conjunctivitis • Associated with EGFRI • Steroid eye drops • Blurred vision • Crizotinib, vandetanib • Most likely secondary to keratitis Cardiac • QT prolongation – Bosutinib, crizotinib, dasatinib, Imatinib, nilotinib, pazopanib, sorafenib, vandetanib – Increase risks: Concurrent QT prolongation drugs, low K+ and low Mg++ • CHF, ventricular dysfunction • Afatinib, lapatinib, panzopanib, vandetanib • Monitoring of EF with ECHO or MUGA, and S/Sx • Hypertension Hypertension • Axitinib, cabozantinib, everolimus, panzopanib, regorafenib, sorafenib, sunitinib, vandetanib • MOA: Not completely known – ? abnormal endothelial function (RAF kinase inhibition) and angiogenesis (VEGF inhibition) • Onset usually within first 6 weeks after initiation of therapy • Management: – Monitor BP q week for first 6 week after initiation of therapy – Interruption and/or dose reduction should be considered – Permanent discontinuation is rare – Standard antihypertensive agents can be selected with caution to avoid agents with potential for CYP450 drug-drug interaction ( e.g. verapamil, diltiazem) – Agents with protection for proteinuria, such as ACE inhibitors are preferred Pulmonary • Interstitial Lung Disease (ILD) • Afatinib, erlotinib, lapatinib, topotecan, vandetanib • s/sx cough, dyspnea, can be fatal • Increase risk if prior ILD • Monitor • Interstitial pulmonary fibrosis • Busulfan, lomustine • Increase risk if >6 mos of therapy or cumulative dose • Cough • Bosutinib, crizotinib, everolimus, sorafenib, sunitinib, vorinostat • Usually associated with edema or pneumonitis • t-RA induced APL syndrome Gastrointestinal • CINV • Mucositis • Diarrhea • GI perforation Anti-emetic Treatment Assessment for Acute CINV Chemotherapy Regimen: – Emetogenic potential of the chemotherapy regimen – Types of CINV (i.e. acute delayed) Patient Assessment: – Patient risk factors – Patient history – Risk for anticipatory CINV MASCC/ESMO Antiemetic Guidelines 2016 Single Oral Agents CINV Management • General Concepts: • Non-parenteral route: PO, PR, Transdermal • ATC schedule for high, mod, or refractory • Avoid long-term use of steroids and NK1 antagonist • Antiemetic Regimens: • High EP = hi dose 5HT3 antagonist +/- NK1 antagonist • Mod EP = mod dose 5HT3 antagonist • Low EP = 5HT3 antagonist
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