TREATMENT AND SYMPTOM MANAGEMENT ONCOLOGY/ ONS COURSES:
---------ONCOLOGIC EMERGENICES--------
------------ONCOLOGIC EMERGENICES----------
heart
A major consideration when giving these drugs is that they can permanently damage the __________________ if given in high doses.
Critzotinib Ceritinib
ALK inhibitors (also called multikinase inhibitors)
Alterations in Integumentary Function
ALTERATIONS IN INTEGUMENTARY FUNCTION
% neutrophils (bands + segments) x WBC
ANC =
ANEMIA
ANEMIA
Anorexia and Cachexia
ANOREXIA and CACHEXIA
tyrosine kinases -Signal transduction inhibitors interfere with this inappropriate signaling. Blocking these cell signals can sometimes help keep the cancer under control.
Activation of receptor _______________, which triggers a biochemical cascade of cell- signaling events. In cancers, these signals are stuck "on" and malignant cells are stimulated to divide continuously without being prompted by outside signals.
serotonin pathways
Acute CINV appears to be mediated primarily by ______________
Acute radiation side effects are caused by damage to rapidly dividing normal cells in the area being treated. These effects include skin irritation or damage at regions exposed to the radiation beams. Examples include damage to the salivary glands or hair loss when the head or neck area is treated or urinary or bowel problems when the lower abdomen is treated.
Acute side effects of RT
*Non-platins:* -Nitrogen mustards: Mechlorethamine, chlorambucil, cyclophosphomide, ifosfamide, and melphalan -Nitrosoureas: Streptozocin, carmustin (BCNU), and lomustine -Alkyl sulfonates: Busulfan -Triazines: Dacarbazine (DTIC) and temozolomide -Ethylenimines: Thiotepa and altretamine (hexmethylmelamine) *Platinum analogs:* -Carboplatin -Cisplatin -Oxaliplatin
Alkylating agent examples
Alkylating agents interfere with DNA replication, RNA transcription, and nucleic acid function. They are cell cycle nonspecific and work in all phases of the cycle.
Alkylating agents MOA
Future Fertility
Alkylating agents also pose a significant threat to ________________ in adolescents and young adults (of child-bearing age).
neutropenia
An ANC less than 500 neutrophils/mcl or less than 1,000 neutrophils/mcl with a predicted decline to less than 500 neutrophils/mcl over the next 48 hours is indicative of
Grade 1 (mild) • Hb 10g/dl (lower limit of normal) Grade 2 (moderate) • Hb 8-10 g/dl Grade 3 (severe) • Hb 6.5-8 g/dl Grade 4 (life threatening) • Life threatening Grade 5 (death) • Death
Anemia grading scale
Daunorubicin Doxorubicin Epirubicin Idarubicin Valrubicin Liposomal formulations Doxorubicin hydrochloride liposome Daunrubicin citrate liposomal
Anthracyclines / Antitumor Antibiotics Examples
Inhibits or stops angiogenesis, causing cell death
Antiangiogenic or anti-vascular endothelial growth factor (VEGF) MOA
bevacizumab pazopanib sunitinib sorafenib axitinib vandetanib
Antiangiogenic or anti-vascular endothelial growth factor (VEGF) agents
Antimetabolites inhibit protein synthesis, substitute erroneous substances needed for DNA/RNA replication, and inhibit DNA synthesis. They are cell cycle specific and damage cells during S phase.
Antimetabolites MOA
5-fluorouracil (5-FU) 6-mercaptopurine (6-MP) *Capecitabine* Cladribine, Clofarabine, *Cytarabine* Floxuridine Fludarabine *Gemcitabine* Hydroxyurea Methotrexate Pemetrexed Pentostatin Thioguanine -bine
Antimetabolites examples
Amifostine (Ethyol)
Approved by the FDA in 1995, amifostine helps reduce the level of renal injury in some cancer patients treated with chemotherapy. It was studied in WWII to protect soldiers against chemical warfare.
Anastrozole (nonsteroidal) Letrozole (nonsteroidal) Exemestane (steroidal)
Aromatase inhibitors
•Stopping or slowing the growth of cancer cells •Stopping cancer from spreading to other parts of the body •Helping the immune system recognize cancer cells and increase its effectiveness at eliminating cancer cells.
As a very broad overview, immunotherapy works by:
• DEXA scan • Complete blood count • Chemistry profile • Protein electrophoresis • Thyroid stimulation hormone testing
Assessment for Osteoporosis
Imatinib Dasatinib Neratinib (Nerlynx) ----------- NERLYNX is a kinase inhibitor indicated for the extended adjuvant treatment of adult patients with early stage HER2-overexpressed/amplified breast cancer, to follow adjuvant trastuzumab-based therapy.
BCR-ABL inhibitors (tyrosine kinase inhibitors)
BIOTHERAPY: IMMUNOTHERAPY and TARGETED THERAPY
BIOTHERAPY: IMMUNOTHERAPY and TARGETED THERAPY
Vemurafenib Dabrafenib
BRAF kinase inhibitors (also called multikinase inhibitors)
Educate the patient to be prepared for short-term side effects that may include: -headaches -hair loss -nausea and vomiting -hearing loss -skin and scalp changes -trouble with memory and speech -seizures. Advise your patient to use only recommended moisturizers and shampoos on scalp to decrease irritation. Protect your scalp with a hat or frequent application of sunscreen if exposed to the sun
Brain radiation information for patients
Advise the patient to avoid bras with underwires, nylon, or lace. Instead, recommend a breathable cotton bra or camisole. Tell patients they may use deodorant but should avoid shaving the armpits to avoid skin irritation.
Breast radiation information for patients
Cancer-Related Fatigue
CANCER RELATED FATIGUE
Cancer Treatment-Induced Diarrhea
CANCER TREATMENT INDUCED DIARRHEA
CHEMOTHERAPY
CHEMOTHERAPY
Cystitis
CYSTITIS
T cell activity
Checkpoint inhibitors are a subclass of mAbs. As a review, mAbs are antibodies that induce cellular destruction by calling for a T-cell response, drawing chemotherapy or radiation to the site, or interfering with the tumor's ability to build a blood supply. Checkpoint inhibitors are mAbs that bind to checkpoints on immune cells and inactivate the inhibition of the immune system, which may enhance __________________ against tumor cells.
*Salivary Gland Damage* Most acute effects disappear after treatment ends, but some (like salivary gland damage) can be chronic or permanent. The drug Amifostine (Ethyol®) can help protect the salivary glands from radiation damage if it is given during treatment. Amifostine is the only drug approved by the FDA to protect
Chronic side effect of RT
•Boost an immune response, meaning the agents capitalize on immune cells already existing within the body. OR •Enable the immune system to recognize and fight the tumor, meaning the agents use substances produced in a laboratory to help the immune system recognize and fight disease.
Classes of immunotherapy include the following: 1. Monoclonal antibodies 2. Vaccines 3. Cytokines 4. Adoptive cell therapy 5. Checkpoint inhibitors Each class has its own specific mechanism of action. However, all are designed to either:
Substance P
Delayed CINV is less well understood but appears to be mediated by _____________. This occurs more often in women and in patients who have had previous CINV
• Complete blood count with differential • Thyroid-stimulating hormone/T4 level • Blood urea nitrogen and creatinine • Electrolyte studies • Liver function tests • Bone scan (if bony metastasis is suspected)
Diagnostic tests to consider include for CRF
• Myelosuppression • Loss of immune cells in the mucosal tissue • Loss of protective saliva
Direct toxicities include primary injury to oral tissue. Indirect toxicities are because of the following:
Cefuxiamb Erlotinib
EGFR inhibitors
These agents work by forming a complex with topoisomerase and DNA resulting in the inhibition and function of the topoisomerase enzyme. The presence of topoisomerase is required for ongoing DNA synthesis, and these drugs work in the late S and G2 phases.
Epipodophyllotoxins MOA
Etoposide (VP-16) Teniposide (VM 26) Camptothecan (CPT) Topotecan hydrochloride
Epipodophyllotoxins examples
Tamoxifen (ER antagonist) Toremifene (selective ER modulator [SERM]) Raloxifene (SERM)
Estrogen receptor (ER) modulators:
• Metabolites in the chemotherapy directly damage epithelial cells during the excretion process. • Intravesicular chemotherapy causes chemical or inflammatory cystitis.
Etiology and pathophysiology Chemotherapy:
• Includes intracavitary and intravaginal radiation • Inflammation begins within 10-14 days. • Hematuria can occur. • Vascular damage may result in diminished bladder capacity. • Late cystitis can cause fibrosis, ulceration, and strictures. • Is dose-specific • Combination with chemotherapy increases risk.
Etiology and pathophysiology Radiation:
•Programmed cell death protein 1 (PD-1) •Programmed death ligand 1 (PD-L1) •Cytotoxic T lymphocyte-associated protein 4 (CTLA-4) These checkpoints limit the immune response and prevent an autoimmune attack on healthy cells. These checkpoints prevent the overstimulation of the immune function and the immune-related destruction of healthy tissues, but they also may provide a mechanism for tumor cells to evade T-cell recognition.
Examples of checkpoints commonly expressed on the surface of immune cells include the following:
*Phase I: Initiation (soon after chemotherapy or radiation begins):* • DNA and non-DNA damage, causing basal and epithelial damage in submucosa • Reactive oxygen species develops, which contributes to injury in later phases. • Mucosa appears normal. *Phase II: Primary damage response:* • DNA damage and cell death in epithelium of mucosa • Transcription factor nuclear factor-kB is activated and amplification of injury occurs. A multitude of genes are activated, including proinflammatory cytokines, tumor necrosis factor-alpha, interleukin-beta, and interleukin-6, causing more cell injury and death. • Patients may still not feel that any damage has occurred. *Phase III: Signal amplification:* • Cytokines amplify the acceleration and amplify the original injury. • Tissue is biologically altered but still may appear normal. *Phase IV: Ulceration:* Fibrous exudates may thinly cover oral ulcers, which then can fill with bacteria. Pain, dysphagia, decreased intake, difficulty talking, increased risk of bleeding *Phase V: Healing:* • When chemotherapy and/or radiation are discontinued, new messenger molecules direct the epithelium to heal and increase white blood cell production to fight local mucosal infection. • The entire cycle may not be accomplished in one cycle of treatment; therefore, patients may remain in phase IV or be beginning phase V when a new cycle of treatment begins, prolonging eventual healing.
Five phases of pathology occur in the development and resolution of mucositis.
Specific to tumor cells Located on the surface of the tumor cells Present in large numbers Involved in tumor cell survival
For a tumor antigen to be best suited for targeted therapy, it should be:
trastuzumab pertuzumab
HER2 inhibitors
HORMONAL THERAPY
HORMONAL THERAPY
HORMONE THERAPY
HORMONE THERAPY
Ifosfamide and Cyclophosphamide
Hemorrhagic cystitis is an adverse side effect or complication related to ___________ and ______________ administration and may occur immediately following conditioning treatment.
-Cisplatin -Combination of either Doxorubicin or Epirubicin with Cyclophosphamide -Cyclophosphamide > 1,500 mg/m2 -Dacarbazine -Probarbazine
High level of Emetogencity chemos
prevent cancer cells from getting the hormones they need to grow
Hormone therapy usually involves taking medications that do what to cancer cells?
A key component of a healthy immune system is the immune checkpoint. Checkpoints are like *traffic lights* that regulate immune function and prevent overstimulation of the immune response. They essentially put the brakes on immune function, preventing overactivation.
How Checkpoint Inhibitors work
Signal transduction inhibitors block signal transduction, which is the process by which a cell responds to signals from its environment. Cell growth, function and apoptosis are regulated through a process called cell signaling.
How do Signal Transduction Inhibitors work?
IMMUNOTHERAPY
IMMUNOTHERAPY
Fevers Chills Body Aches (flu-like symptoms) Nausea and Vomiting Loss of Appetite Fatigue
Immunotherapy Side Effects: the most common side effects are the result of the "revving up" and stimulation of the immune system. They include:
ferritin level below 30 ng/ml and transferrin saturation (TSAT) below 20%. --Treatment via IV or oral supplements are preferred, both without erythropoietin-stimulating agents (ESAs).
Iron monitoring and supplements for absolute iron deficiency. Defined as ferritin and Transferrin saturation of?
dermatologic and gastrointestinal
It is not surprising to see _____________ and ________________ irAEs cited most frequently because immune cells are particularly active in those areas.
Sorafenib, Dabrafenib Trametinib Vemurafenib
Kinase inhibitors target the RAF/RAS/MET pathway. Examples:
LYMPHEDEMA
LYMPHEDEMA
•Fibrosis (the replacement of normal tissue with scar tissue, leading to restricted movement of the affected area) •Damage to the bowels, causing diarrhea and bleeding •Memory loss •Infertility (inability to have a child) •Rarely, a second cancer caused by radiation exposure
Late side effects of RT
Assessment should include measurements of the affected limb using a non-stretch tape at intervals of 4 cm from wrist to axilla (if arm). Assessment should be performed on a regular basis and with a consistent method of measurements to assess response to therapy
Lymphedema assessment
Management of Cancer-Related Pain
MANAGEMENT OF CANCER RELATED PAIN
TKIs bind to the tyrosine kinase in EGFR, inactivating it or limiting its activity. Monoclonal antibodies with TKI capabilities bind to the extracellular component of EGFR to prevent the actual substrates from binding to the receptors, inhibiting EGFR activation.
MOA of TKI's
MUCOSITIS
MUCOSITIS
Anorexia Recommended for practice • Corticosteroids • Progestins Likely to be effective: • Nutritional counseling Cachexia • Recommended for practice • Treat underlying etiology if possible (obstruction). • There is no evidence that paraneoplastic cachexia is reversible. • Enteral or parenteral supplements • Corticosteroids • Progestins • Metoclopramide • Cannabinoid derivatives • Treatment of associated symptoms
Management of Anorexia and Cachexia
Recommended: Chemotherapy-induced diarrhea -Loperamide -High-dose loperamide if treated with irinotecan -Somatostatin analog if refractory to loperamide Radiation-induced diarrhea -Oral opiates Likely to be effective: Chemotherapy-induced diarrhea: -Octreotide/IM long-acting if refractory to loperamide Prevention of radiation-induced diarrhea: -Probiotic supplements -Psyllium fiber Radiation-induced diarrhea: -Octreotide if grade 2 or 3
Management of Cancer Treatment-Induced Diarrhea
Pharmacologic • Antidepressants • Psychostimulants • Corticosteroids Nonpharmacologic • Physical activity • Rest periods • Stress-reduction techniques • Cognitive behavioral therapies Management: Comorbidities contributing to fatigue • Endocrinopathies • Cardiopulmonary dysfunction • Impaired sleep quality • Deconditioning • Concurrent symptoms (pain, nausea, depression)
Management of Cancer-Related Fatigue
Recommended • Complete decongestive therapy (CDT) • Compression bandages • Prompt treatment of infections Likely to be effective • Maintain optimal body weight. • Manual lymph drainage • Impeccable skin care
Management of Lymphedema
• Cough suppressants • Antipyretics • Glucocorticoid therapy may be used and then tapered to avoid symptom flare • Cautious use of oxygen • Establish fluid homeostasis • Bronchodilators • Elevate head of bed Pulmonary fibrosis can occur as a late effect of thoracic radiation exposure and is chronic in nature. It can occur 6-24 months after completion of therapy.
Management of Pulmonary Toxicities
• Thorough dental examination prior to initiation of therapy • Meticulous teeth brushing and flossing (if hematologically stable) • Avoid spicy, rough foods, and harsh chemicals. • Limit sugar intake. • Pain management • Saliva substitutes/increase fluid intake • Prophylactic antibiotic coverage • Sialagogues • Amifostine
Management of Xerostomia
Prevention is key. • Adequate hydration and diuresis to remove metabolites from the urine • Take oral cyclophosphamide early in the day to allow for increased hydration and diuresis of metabolites prior to evening • Mesna IV as uroprotectant if taking ifosfamide or high-dose cyclophosphamide • Amifostine as cytoprotectant if taking cisplatin • Hydration • Treat infections • Avoid alkalizing agents • Antispasmodics • Analgesics for pain control • Avoid caffeine, spicy foods, coffee, and alcohol • Continuous bladder irrigation • May include hyperbaric oxygen therapy
Management of cystitis:
Treatment is determined based on severity of symptoms (grade) Mainstay of treatment includes topical steroids, antibacterials, and moisturizers If infection is suspected, always perform a culture and determine sensitivities *Low-grade toxicity management*: • Alcohol-free over-the-counter moisturizing creams or ointments twice daily • Sunscreen SPF 15 or greater applied to exposed areas of body; reapply every two hours when outside • Topical low or moderate potency steroid to the face and chest twice daily • Topical or oral antibiotics or oral low-dose steroids as indicated *Severe toxicity management*: • Stop topical antibiotic if being used. • Begin oral antibiotic for six weeks (tetracycline) and topical low or moderate potency steroid • Isotretinoin at low doses (20-30 mg per day)
Management: Acneiform Rash
For grade 1 and 2 or greater toxicities: •Consider minoxidil 5% twice daily during chemotherapy, biotin 2.5 mg daily, and orthosilicic acid 10 mg daily after chemotherapy is completed. •Counsel the patient on the use of hats, scarves, and wigs.
Management: Alopecia
Key points • Treatment is determined based on severity of symptoms (grade). • Mainstay of treatment includes topical steroids, antibacterials, and moisturizers. • If infection is suspected, always perform a culture and determine sensitivities. Management • Maintain hygiene, gently clean and dry skin in radiation field shortly before each radiation treatment, no topicals within four hours of radiation therapy. Use topical high-potency steroid daily for the duration of radiation. • Concurrent oral antibiotics, as indicated • Topical steroids • Topical high-potency steroid daily and topical antibiotic (mupirocin or silver sulfadiazine) to moist desquamative areas twice daily • Topical high-potency steroids daily and topical antibiotic to moist desquamative areas twice daily and pain control with nonsteroidal anti-inflammatory drugs, GABA receptor agonists, and narcotics • No evidence exists to support the use of trolamine, aloe vera, sulcrate and its derivitives, despanthenol, asorbic acid, combination preparations, almond oil, and chamomile cream for prevention or management.
Management: Radiation Dermatitis
*Key points* •Treatment is determined based on severity of symptoms (grade). •Mainstay of treatment includes topical steroids, antibacterials, and moisturizers. •If infection is suspected, always perform a culture and determine sensitivities *Management of xerosis: Increasing intervention with severity:* •Moisturizing cream or ointment to face and ammonium lactate 12% cream or salicylic acid 6% cream •Topical moderate to high potency steroid to eczematous areas *Management of pruritis: Increasing intervention with severity* •Topical moderate to high potent steroids or topical antipruritics with menthol and oral antipruritics •Oral antipruritics and oral corticosteroids oral gabapentin or pregabalin with or without phototherapy *Management of paronychia:* •Topical high potency steroid and vinegar soaks, topical iodine or combined topical steroid and antibiotic and antifungal agent •Oral antibiotics with anti-Staphylococcus aureus and gram-positive coverage •Nail avulsion
Management: Xerosis, Pruritus, and Paronychia
• Busulfan • *Capecitabine* • *Cyclophosphamide* • *Doxil* • 5-fluorouracil • Mechlorethamine *DOXIL® is a specially coated form of doxorubicin HCl that covers the active agent, doxorubicin HCl, with 2 layers of protective coating called STEALTH® technology
Many chemotherapeutic agents can cause or contribute to mucositis. Some of the most commonly implicated are listed below:
ifosfamide and high dose cyclophosphamide
Mesna should be given to patients receiving _____________ and __________________ to decrease possibility of hemorrhagic cystitis associated with its administration.
-Carboplatin -Oxaliplatin -Cyclophosphamide (oral) and Cyclophosphamide <1500 mg/m2 -Cytarabine > 1g/m2 -Daunorubicin -Doxorubicin -Epirubicin -Idarubicin -Ifosfamide -Etoposide (oral) -Irinotecan -Arsenic Trioxide
Moderate level of Emetogencity chemos
Nausea and Vomiting
NAUSEA AND VOMITING
A type of therapy that uses substances to stimulate or suppress the immune system to help the body fight cancer, infection, and other diseases. Some types of immunotherapy only target certain cells of the immune system. Others affect the immune system in a general way
NCI defines immunotherapy as:
A type of treatment that uses drugs or other substances to identify and attack specific types of cancer cells with less harm to normal cells. Some targeted therapies block the action of certain enzymes, proteins, or other molecules involved in the growth and spread of cancer cells. Other types of targeted therapies work with the immune system to kill cancer cells or deliver toxic substances directly to the cancer cells and kill them.
NCI defines targeted therapy as:
NEUTROPENIA
NEUTROPENIA
Nutritional Screening and Assessment
NUTRITIONAL SCREENING AND ASSESSMENT
Attaches to antigen expressed by specific cancer cells, acting as a marker for the body's immune system to destroy the cells.
Naked MOABS MOA
•Alemtuzumab (antigen targeted: CD52) •Trastuzumab (antigen targeted: HER2) •Rituximab, alemtuzumab, tositumomab, obinutuzimab (antigen targeted: CD20) •Imatinib mesylate (antigen targeted: Philadelphia chromosome)
Naked MOABs and targeted agents (can work alone without assistance from other agents)
•Tricyclic antidepressants •Calcium channel alpha-2-delta ligands (gabapentin, pregabalin) •Topical therapy (lidocaine)
Neuropathic pain medications
Height Weight Body fat composition Related laboratory values (e.g., serum protein, iron, blood urea nitrogen, creatinine)
Nutritional assessment includes:
Osteoporosis and Cancer Treatment-Induced Bone Loss
OSTEOPOROSIS and CANCER TREATMENT INDUCED BONE LOSS
Peripheral Neuropathy
PERIPHERAL NEUROPATHY
Drug names end in -lisib Taselisib Alpelisib Taselisib and alpelisib were both tested in women with hormone-receptor-positive, HER2-negative advanced breast cancer with PIK3CA tumor mutations. Both are taken as once-daily pills in combination with the estrogen-blocking medication Faslodex (fulvestrant).
PI3K inhibitors drug examples and easy identification
The PI3K pathway regulates cell survival and proliferation. When abnormal activation of this pathway occurs, scientists identified survival and proliferation of tumor cells in many cancers.
PI3K inhibitors target the PI3K pathway explained
Vinca Alkaloids Epipodophyllotoxins Taxanes
PLANT TAXANES: Class examples
*Platinums*: -Cisplatin: Cumulative-dose related; may occur late in treatment course or after completion of treatment Symptoms include Lhermittes sign in the neck, down the legs, and in the back with flexion of the neck. Recovery may take as many as two years. The majority of patients will recover fully. -Oxaliplatin: Similar to cisplatin Symptoms include pharyngo-laryngo-dysesthesia that is aggravated by cold exposure, dysesthesias of hands and feet, feeling of jaw tightening, and feeling of loss of breath. 80% of patients on oxaliplatin will experience effects; 40% will recover within 6-8 months. *Taxanes*: -Occurs in up to 60% of patients Sensory-motor PN, increases with cumulative doses Can develop only 1-3 days after treatment *Vinca alkaloids*: -Risk is related to type and cumulative dose. -Paresthesias in hands and feet are common; loss of pain and temperature sensation. *Proteasome inhibitors* : -PN may be dose-limiting for patients who receive bortezomib for multiple myeloma. -Many patients who receive bortezomib may already have been pretreated with neurotoxic agents; toxicity may be greater in this population. (Binner et al., 2011)
PN is most often associated with certain chemotherapies.
PULMONARY TOXICITY
PULMONARY TOXICITY
Damage from known risk factors causes injury to the large and small fibers that carry sensation for light touch, as well as the myelin sheath around the axon. Damage is at the cellular level, which may be why it is sometimes irreversible. Nerve conduction velocity is then reduced when the axon no longer has its myelin sheath.
Pathophysiology and Symptoms of PN
Pathophysiology of CRF The pathophysiology of CRF remains unknown, likely because of the multitude of factors that may contribute to it. It is most likely a side effect of treatment, as well as a biologic effect from cancer itself. Contributing factors: • Underlying disease • Chemotherapy • Radiation therapy • Surgery • Biotherapy • Cytokines • Performance status • Anemia • Infection • Malnutrition • Metabolic disturbance • Sleep disorders • Depression
Pathophysiology of CRF
•Several neuronal areas in the medulla of the brain are involved in the nausea and vomiting process. •Afferent impulses from the chemoreceptor zone, the pharynx, GI tract, and cerebral cortex trigger the vomiting center in the medulla. •Chemotherapy causes release of serotonin (5-HT3) through the GI pathway of the GI tract. •*Serotonin binds to serotonin receptors on the vagus nerve in the GI tract*. •*Neurotransmitter substance P is also involved in the CINV pathway, binding to neurokinin-1 receptors in the central nervous system*. •Other chemicals implicated in the emesis pathway include dopamine and cholecystokinin.
Pathophysiology of Chemotherapy-Induced Nausea and Vomiting
Anorexia—tumor burden, response to treatment, slowed GI motility, pain, distress, fatigue Cachexia Primary etiology: Paraneoplastic syndrome of wasting that is mediated through cytokines Secondary etiology: Barriers to intake of food lead to wasting, altered fat metabolism, inefficient use of glucose, and decreased protein mass
Pathophysiology of anorexia and cachexia
•Massage, physical therapy, electrical stimulation •Pain management •May include clonidine, anticonvulsants, tricyclic antidepressants, SSRI antidepressants, corticosteroids, and local anesthetics
Pharmacologic and nonpharmacologic and associated symptom management (without evidence-based outcome data) include the following:
•Maintain 10,000 (10 x 103 per mcl) for most patients. •Maintain 20,000 (20 x 103 per mcl) for those undergoing minor procedures. •Maintain 40,000-50,000 (40-50 x 103 per mcl) for those undergoing major surgery. •Transfuse patients who are experiencing active bleeding.
Platelet transfusion: Guidelines for threshold of when to transfuse are based on patient risk for bleeding and clinical setting.
Dyspnea tachypnea dry cough anxiety hypoxemia hemoptysis pleuritic pain use of accessory muscles to breathe Diagnostics: Chest radiograph, arterial blood gases, pulmonary function testing
Pneumonitis Symptoms
*Pamidronate disodium for injection (AREDIA)* •Indicated to treat osteolytic lesions in multiple myeloma, hypercalcemia of malignancy, Paget's disease, and bone metastases from breast cancer *Zoledronic acid for injection (RECLAST)* •Can be administered at the same time as chemotherapy •Is given as soon as bone metastases are found and then continued every 3-4 weeks •Indicated to treat both osteolytic and osteoblastic lesions such as multiple myeloma, hypercalcemia of malignancy, and bone metastases from all solid tumors *Denosumab for injection (XGEVA and PROLIA)* •Indicated for the prevention of skeletal-related events in patients with bone metastases from solid tumors
Prevention and Treatment of Skeletal Symptoms Bisphosphonate IV therapy:
two to four days
Prophylactic dexamethasone and aprepitant should be given for those receiving highly emetogenic drugs through the period when delayed emesis could occur, typically ______ to _______ days after completion of the chemotherapy cycle.
RT
RADIATION THERAPY OVERVIEW
• Protein • Calcium • Magnesium • Vitamin D • Phosphorus • Other trace elements
Regulating factors in proper bone remineralization include the following:
SYMPTOM MANAGEMENT------------------------
SYMPTOM MANAGEMENT-------------------
Myelosuppression Peripheral Neuropathy Nausea Vomiting
Significany side effects of Vinca Alkaloids
monoclonal antibodies (mAbs). mAbs are a passive (meaning they do not result in any immunologic memory) but specific (meaning they target specific cancer cells) class of immunotherapy. Clinical trial data suggest that, when used with combination chemotherapy/radiation therapy, monoclonal antibodies significantly improve response rates
Some cancer cells have tumor-specific antigens on their surfaces, and researchers designed antibodies that specifically target these antigens. They can then make many copies of that antibody in the laboratory exogenously. These are known as ________________________.
-Block the hormones from acting by blocking the receptor on the cells. Cells have receptors on their surface, where certain hormones bind and subsequently trigger activity inside the cells. By blocking the receptor, the hormone is not able to connect to its receptor and, therefore, cannot activate the cell. -Prevent the body from producing the hormone by taking a medication that blocks production of the hormone. -Eliminate the hormone receptors on the cell surface or change their shape, therefore making it impossible for the hormone to properly attach itself to the cell receptor and to activate it, rendering the hormone unable to function.
Some cancers are driven by hormones and may rely on them to grow. Blocking the action of these hormones could potentially stop the cancer from growing. There are a few ways in which this can be achieved:
Bevacizumab Sorafenib Sunitinib *Bevacizumab* -specifically recognizes and binds to VEGF *Sorafenib and sunitinib* - bind to receptors on the surface of endothelial cells or to other proteins in the downstream signaling pathways, blocking their activities.
Some examples of angiogenesis inhibitors used in the treatment of cancer include:
-Antiestrogens (e.g., tamoxifen, fulvestrant) -Aromatase inhibitors (e.g., anastrozole, exemestane) -Antiandrogens (e.g., bicalutamide, flutamide) -Luteinizing hormone releasing hormone (LHRH) agonist (e.g., goserelin, leuprolide)
Some examples of hormone therapies used in the treatment of cancer include:
fatigue anorexia mucositis xerostomia alopecia skin reaction nausea and vomiting esophagitis and dysphagia diarrhea cystitis bone marrow suppression
Some examples of radiation therapy side effects
EGFR inhibitors (e.g., cetuximab, erlotinib) HER2 inhibitors (e.g., trastuzumab, pertuzumab) BCR-ABL inhibitors (also called tyrosine kinase inhibitors) (e.g., imatinib, dasatinib) ALK inhibitors (also called multikinase inhibitors) (e.g., crizotinib, ceritinib) BRAF kinase inhibitors (also called multikinase inhibitors) (e.g., vemurafenib, dabrafenib)
Some examples of signal transduction inhibitors used in the treatment of cancer include:
neutrophils
Some of the subtypes of WBCs are known as granulocytes, of which _________________ are typically the most common, accounting for about 60% of WBCs. These are the first cells to respond to an infection.
• Fatigue: The nurse can assess the contributing factors and encouraging patient to prioritize and delegate responsibilities and promote gentle daily exercise. • Anorexia: The nurse can provide education to the patient to eat small, frequent meals; change diet and environment; stimulate appetite (e.g., with medication); eat nutritious and high-protein snacks; avoid fatty or greasy foods; and take nutritional supplements. • Mucositis: This may involve mouth soreness or white patches in the oral cavity that may bleed if disturbed. The nurse can educate the patient to avoid irritants, such as alcohol, tobacco, spicy and acidic foods, or hot drinks. Eating a soft or liquid diet and oral care with saline or water frequently are essential parts of patient education. • Xerostomia: This is associated with dry mouth resulting from radiation to salivary glands and can alter patient taste. Nursing care may include advising the patient to moisten foods; use artificial saliva; avoid dry foods; soak foods in coffee, milk, or warm drinks; and promote frequent mouth care with saline. • Alopecia: This is the loss of hair associated with radiation of the head. Nursing care may include advising patients to gently brush and comb and decrease frequency of shampooing and avoid using hair dye or chemicals, as well as giving psychological support for change in body image and giving advice, such as using a wig if necessary. • Nausea and vomiting: Some suggestions to manage this symptom include eating small, frequent meals; drinking clear or cool beverages; avoiding eating overly sweet, greasy, or high fat foods; resting with the head elevated after eating; and taking antiemetic medications if necessary. • Bone marrow suppression: If a large bone is within the field of radiation, myelosuppression can potentially occur as a result of RT. The nurse may consult with the physician for a weekly blood count monitoring and educating the patient to observe signs and symptoms of bleeding and infection. Advise patients that blood products transfusion might be necessary.
Symptom management of patients on RT Therapy:
gram negative bacteria
Symptoms may be absent or diminished in patients with a neutropenia-associated infection. Most febrile neutropenia is caused by nosocomial infection of _____________________, and more than 80% of infections are from the patient's own normal flora.
• Suprapubic pain or pressure • Abdominal pain • Urinary urgency or frequency, burning with urination • Hematuria • Bladder spasms • Incomplete bladder evacuation
Symptoms of Cystitis
• Edema • Increasing tightness of clothes or jewelry on affected limb • Stiffness • Numbness or paresthesia of affected limb • Pain • Increasing weakness of affected limb • Erythema
Symptoms of Lymphedema
• Mucosal changes: pallor, white patches, erythema, lesions • Change in saliva texture, quantity • Foul odor • Cracks, fissures in mucosa • Difficulty swallowing, talking, eating • Pain • Changes in voice quality
Symptoms of Mucositis
Fatigue is a common side effect of RT regardless of which part of the body is treated. It can occur during treatment and may become a chronic problem, experienced for weeks, months, and years following the completion of treatment. Nausea with or without vomiting is common when the abdomen is treated and occurs sometimes when the brain is treated. Medications are available to help prevent or treat nausea and vomiting during treatment.
Systemic side effects of RT
TARGETED THERAPY
TARGETED THERAPY
THROMBOCYTOPENIA
THROMBOCYTOPENIA
*Infusion reactions or hypersensitivity *Skin reactions *Cardiovascular effects *Bleeding and clotting abnormalities *Wound healing interference Infusion reaction or hypersensitivity -Severe hypersensitivity (or infusion reactions) are rare, but many targeted agents require premedication, close monitoring, and prompt intervention when symptoms do occur. Reactions may be immediate, delayed, or may occur in later infusions. Management includes temporary infusion interruption, reduction of the infusion rate, and symptom management. Re-challenge may be considered depending on the agent and clinical patient factors. Skin reactions -Some targeted drugs, particularly EGFR inhibitors, can cause rashes or other skin changes. These problems usually develop slowly over days or weeks. These may include acneiform rash, dry skin, nail changes, and hair depigmentation. Cardiovascular effects -Some targeted drugs, especially anti-angiogenic agents, cause hypertension. HER2 inhibitors can damage the heart, potentially causing chest pain, coughing, dyspnea, fluid retention, dizziness, and fainting. Bleeding and clotting abnormalities -Anti-angiogenic agents can cause increased bruising and bleeding, which may become life threatening. These drugs can also cause clotting deficiencies or dysfunction, manifested as thrombotic events. Impaired wound healing Anti-angiogenic agents can interfere with wound healing in old and new wounds. Planned surgeries and dental procedures need to be considered. Gastrointestinal perforation may also occur as a result, leading to a life-threatening situation.
Targeted Therapy Side Effects: Most common
-Targeted therapies act on specific molecular targets that are associated with cancer, whereas most standard chemotherapy agents act on all rapidly dividing normal and cancerous cells. -Targeted therapies are deliberately chosen or designed to interact with their target, whereas many standard chemotherapy agents were identified because they kill cells. -Targeted therapies are often cytostatic (that is, they block tumor cell proliferation), whereas standard chemotherapy agents are cytotoxic (that is, they kill tumor cells).
Targeted therapies differ from standard chemotherapy in several ways:
Blocking angiogenesis Blocking signals inside or outside the cell Delivering toxic substances to the cell
Targeted therapies work by:
Taxanes are mitotic inhibitors derived from the Pacific yew tree. They can stop mitosis or inhibit enzymes from making proteins needed for cell reproduction. These drugs work during the M phase to inhibit the microtubules necessary for division; it is also active in the G1 to S transition phase, a last checkpoint after which cell division cannot be stopped.
Taxanes MOA
peripheral nerve damage
Taxanes are known for their potential to cause _______________________, which can be a dose-limiting side effect.
Paclitaxel Docetaxel Cabazitaxel Paclitaxel protein bound
Taxanes examples
G0 phase (resting stage): -The cell has not yet started to divide. G0 can last from a few hours to a few years. When the cell gets a signal to reproduce, it moves into the G1 phase. G1 phase: -During this phase, the cell starts making more proteins and growing larger, so the new cells will be of normal size. This phase lasts from 18-30 hours. S phase: -In the S phase, the chromosomes containing the genetic code (DNA) are copied, so both of the new cells formed will have matching strands of DNA. The S phase lasts from 18-20 hours. G2 phase: -In the G2 phase, the cell checks the DNA and gets ready to start splitting into two cells. This phase lasts from 2-10 hours. M phase (mitosis): -In this phase, which lasts only 30-60 minutes, the cell actually splits into two new cells.
The Cell Cycle
Parotid -Damage can occur in as little as one week of radiation exposure
The ______________ gland is highly radiosensitive; therefore, radiation therapy fields in which the parotid gland is involved will cause direct damage to saliva-producing cells, producing a permanent effect if originating from surgery or radiation and an acute, temporary effect if from a side effect of chemotherapy
overstimulated immune system. -They frequently are referred to as immune-related adverse events (irAEs), although they typically are low-grade and manageable with careful assessment and early intervention.
The adverse events seen with checkpoint inhibitors are often a direct result of their mechanism of action, inhibiting or downregulating immune system checkpoints to enhance T cells' anticancer response. Therefore, adverse events often are the results of an _______________________.
1. growth factors and growth factor receptors 2. tyrosine kinase receptors
This signal can be come from outside the cell (__________1_________) or inside the cells (________2_______)
150,000 per mcl -May occur 8-14 days after chemotherapy and related to suppression of bone marrow
Thrombocytopenia refers to a platelet count less than ____________________________
Grade 1 Erythema of the oral mucosa Grade 2 Patchy ulcerations or pseudomembranes (a thick, tough fibrinous exudate on the surface of a membrane) Grade 3 Confluent ulcerations or pseudomembranes; bleeding with minor trauma Grade 4 Tissue necrosis; significant spontaneous bleeding; life-threatening consequences Grade 5 Death
Toxicity Grading Scale for Mucositis
Bisphosphonates: -Alendronate -Ibandronate -Risedronate -Zoledronic Acid Receptor Activator for Nuclear Kappa B Ligand Antibody: -Denosumab Other Agents: -Calcitonin -Teriparatide
Treatment for Cancer Treatment-Induced Osteoporosis
•*Osteolytic lesions*: Common in multiple myeloma, lung, thyroid, breast, and kidney tumors; most often associated with pathologic fractures •*Osteoblastic lesions*: Common in prostate and breast cancers. Tumor cells cause overproduction of osteoblasts causing rigid, inflexible bone formation that is not deposited near the areas of bone resorption, resulting in decreased bone strength and increased risk of vertebral collapse.
Types of bone metastases
*Antigen targeted*: Epidermal growth factor receptor (EGFR) that has a major role in controlling normal cell growth, apoptosis, and other cellular functions; mutations can cause cancer development. -Examples: cetuximab gefitinib erlotinib *lapatinib* panitumumab vandetanib zivaflibercept
Tyrosine kinase inhibitors (TKIs) and tyrosine kinase inhibiting MOABs:
Drug names end in -tinib
Tyrosine kinase inhibitors (TKIs) and tyrosine kinase inhibiting MOABs: How to easily identify these drugs
Grade Description 0 (none) = None I (mild) = Oral soreness, erythema II (moderate) = Oral erythema, ulcers, solid diet tolerated III (severe) = Oral ulcers, liquid diet only IV (life-threatening) = Oral alimentation impossible
WHO Oral Mucositis Grading Scale
*Mechanism of action:* - Trigger pluripotent stem cells in the bone marrow to produce more of a particular white blood cell. Stimulate hematopoietic development of granulocytes, reducing the duration of neutropenic episodes. *Potential side effects* -Pain to long bones, injection site pain, allergic reaction
White blood cell stimulants (granulocyte CSFs [GCSFs]) for chemotherapy-induced neutropenia MOA
Step 1: Nonopioid analgesics (mild pain) (ibuprofen, aspirin, nonsteroidal anti-inflammatory drugs) Step 2: Opioid analgesics with or without nonopioid analgesics (mild to moderate pain) (hydrocodone and oxycodone in fixed combinations with acetaminophen or aspirin); avoid darvon because the metabolite may cause central nervous system toxicity. Step 3: Opioid analgesics with or without nonopioid analgesics (moderate to severe pain) (morphine, oxycodone, hydromorphone, fentanyl); avoid demerol because the metabolite may cause central nervous system toxicity.
World Health Organization Analgesic Ladder to Manage Pain
XEROSTOMIA
XEROSTOMIA
• Difficulty speaking or swallowing • Feeling of gagging or choking • Pain • Halitosis; periodontal disease • Cheilitis or lip inflammation/chapping • Burning sensation of the tongue • Increased oral infections
Xerostomia- Symptoms will vary, but may include the following:
Fatigue
_____________ is a common side effect of RT regardless of which part of the body is treated. It
Osteonecrosis
__________________ of the jaw is an uncommon adverse effect in patients receiving complex treatment regimens, including bisphosphonates. These patients will have exposed bone in the jaw that occurs after dental surgery or spontaneously and are slow to heal or may not heal at all.
Everolimus (Zortress)
__________________, an mTOR inhibitor, is currently approved for the treatment of hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer
Vinca Alkaloids
____________________ are cytoxic to the microtubules and cell cycle arrest in metaphase, predominantly M phase.
Antitumor antibiotics -Anthracyclines
_____________________are used to treat hematologic and various types of solid tumors. Antitumor antibiotics interfere with enzymes required for DNA replication and are cell cycle nonspecific.
Flag cancer cells for destruction Block growth signals and receptors Deliver other anticancer agents to the site of the tumor •*Flag cancer cells for destruction*: mAbs can attach themselves to the surface antigens on tumor cells. This serves as a beacon to the immune system to induce cellular destruction. •*Block growth signals and receptors*: mAbs can block the pathway used by cancer cells to grow their own blood supplies, cutting off a source of energy and nutrition for the cancer cell. •*Deliver other anticancer agents to the site of the tumor*: mAbs can be bound to other drugs or radiation particles and delivered directly to the cancer cell. The cancer cell will engulf the mAb and begin to digest it, or break it down. The attached chemotherapy or radiation particle then induces the cellular death of the cancer cell.
mAbs work in a variety of ways:
10%
• Many patients have recent weight loss at the time of diagnosis. Consult a dietitian for patients experiencing signs of malnutrition, weight loss of greater than ________, and those at risk for significant nutritional status decline with development of cachexia.
