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ONS/ONCC CHEMOTHERAPY IMMUNOTHERAPY
CERTIFICATE EXAM WITH VERIFIED QUESTIONS AND
ANSWERS
Interphase and Mitotic Phase - ANSWERS-Cell division produces two identical cells through these two major phases During interphase: - ANSWERS-Cell grows and DNA is replicated through the following three steps: 1: First growth phase (G1 or first gap) 2: Synthesis phase (S phase) 3:Mitotic Phse (M phase) First Growth Phase (G1 or first gap) - ANSWERS--cells increase in size
- reproduce RNA
- "quality assurance" test that the cell will be ready to synthesis DNA
- Length of time is variable, can be from hours to days Synthesis Phase (S phase) - ANSWERS--DNA replicates
- Results in the formation of identical pairs of DNA (chromatids)
- which are attached a t the centromere
- lasts 2-10 hours Mitotic Phase (M phase) - ANSWERS--Replicated chromosomes are aligned, separated, and move into 2 new, identical daughter cells
- takes about 30-60 minutes Major points of cell regulation are entry and exit from - ANSWERS--G1 checkpoint
- S Phase
- G2 checkpoint
- M phase Lesson 1: Foundations to Set the Stage - ANSWERS- Focusing on Cellular Structure and Function - ANSWERS- The Normal Cell Cycle - ANSWERS--The cell cycle refers to the ordered seres of processes of DNA replication and mitosis, or cell division
- Cell nucleus regulates these processes by gathering and processing complexes molecular information Restriction Point - ANSWERS--The transition from the resting phase into an actively dividing phase (G0- G1) is a point where cellular transformation can occur
- During this time, cells pass through a transition phase known as a restriction point
- Cyclin-dependent kinases (CDKs)
- Cyclin-CDK complex allows the cell to progress through each phase of the cell cycle Locations of proteins Cyclins (D, E, A, B) and CDKs - ANSWERS--(G0-G1) : Cyclin D and CDK 4/
- Early S: Cyclin E and CDK 1/
- Late S: Cyclin A and CDK 1/
- G2: CDK 1/2 and cyclin A
- Before M: CDK 1 and Cyclin B Inhibitory proteins - ANSWERS--prevent progression of the cycle when DNA damage is detected
- An example of an inhibitory protein is p53 (AKA TP53) DNA Damage Checkpoints - ANSWERS--If DNA damage is present, cells are programmed to stop dividing or undergo apoptosis (programmed cell death)
- The retinoblastoma protein (Rb), p53, and p21 are some of the most well-understood inhibitory proteins (IP) Inhibitory proteins p53 - ANSWERS--Levels of this IP regulate several important target genes
- Will increase when DNA damage is present
- Protects against inappropriate signal proliferation
- sometimes called the "suicide gene" M Phase Checkpoints - ANSWERS-When the cells prepare to divide, the chromosomes line up in the mitotic spindle. If the chromosomes are not properly aligned, division is not allowed to continue Immunity - ANSWERS- Cells of the Immune System - ANSWERS- Pluripotent Stem Cell - ANSWERS--The cells of the immune system are created in the bome marrow from what is know as a ___
- A stem cell that can differentiate into any cell type except for extraembryotic tissue, does not yet have a function Myeolid Precursor Cells - ANSWERS-Mature into:
- RBCS
- Plts
- WBCs (Granulocytes) Lymphoid Precursor Cells - ANSWERS-Mature into:
- Specialized WBCs called lymphocytes (Agranulocytes) Lines of Defense: The Immune System's Response to Attack - ANSWERS-Consists of 2 types of immunity: 1: Innate 2: Adaptive
- Regulatory T-cells Humoral Immunity - ANSWERS--B-Cells
- Memory B-Cells
- Plasma act to produce immunoglobulins (Igs) or antibodies B-Cell - ANSWERS--each one is programmed to make one specific antibody
- Can recognize antigens whether they are freely circulating in the blood or attached to surface of a microbe
- When dividing, can become plasma cells which will then begin secreting antibodies that are unique to that antigen Plasma Cells - ANSWERS--some plasma cells will undergo apoptosis
- Some will go to the BM where they will continue to secrete antibodies sometimes for years Cell-Mediated Immunity - ANSWERS-Depends upon cytotoxic T cells and helper T cells and their cyokinds
- more effective against antigens within cells Regulatory T-cells AKA suppressor T-Cells - ANSWERS-regulate the immune response to prevent autoimmune reactions and limit inflammatory responses T-Cell - ANSWERS--Can only recognize antigens when they are presented to them by "presenting cells"
- Recognize phagocytized fragments of an antigen that are put on the surface of antigen-presenting cells
Helper T-Cells (CD4+) - ANSWERS--help other T-Cells by secreting chemicals
- Help B Cells to respond
- rapidly divide, in an effort to stay ahead of the antigen dividsion
- some will turn into effector cells, which secrete different kinds of cytokines
- respond similarly to B-Cells Cytotoxic T-Cells (CD8+) - ANSWERS--Directly kill cells for which they are activated to kill
- rapidly divide, become mature cells, and start killing antigens Cytokines - ANSWERS--Secreted by lymphocytes
- Tasked with eliminating the antigen
- Multifunctional subsances having proinflammatory, anti-inflammatory, and regulatory functions in the immune system Cytokines Include.. - ANSWERS--Interferons (IFNs)
- Tumor necrosis factors
- Transforming GFs
- Interleukins (IL - 1, - 2, - 3, - 4, - 6, - 8, - 10, and - 15)
Oncogene - ANSWERS-when mistakes in copies of DNA can occur, if a mutation occurs next to a proto- oncogene, it can "turn on" and become a ______ Examples of oncogoenes - ANSWERS-1. EGFR or Erb-B1 (codes for an epidermal GF receptor in the receptor-tyrosine kinase family ad is associated with head and neck and colorectal cancers)
- EGFR inhibitor therapies are known to cause cutaneous reactions
- Erb-B2 or HER2/neu (codes for an EGFR protein in the tyrosine kinase family and is associated with some breast cancers) Tumor suppressor genes - ANSWERS--act like brakes in a car, slowing down or stopping cell growth and division
- in the presence of malignancies, they bind to DNA with intention of repairing or activating apoptosis
- for it to be turned on it must be expressed or "opened" in the DNA helix so that it can be transcribed or copied p53 - ANSWERS--"sucidie gene"
- activates apoptosis when the cell is damaged beyond repair or too old to function
- more than 50% of solid tumors, the gene is mutated and unable to perform its normal function Growth Signals - ANSWERS--cancer cells are able to find their own growth signals making them self- sufficient Signal transduction - ANSWERS--the communication or passage of a message telling the cell to do a biologic process, such as make a protein, divide, or make new blood vessels
Signal transduction steps - ANSWERS-1. Messages usually sent from outside the cell where the messenger (ligand) first binds to the cell receptor which extended through the cell membrane
- These receptors ae called receptor tyrosine kinases
- To send the message through the membrane, the receptor often has to join with another recetor to become active and t autophophorylate
- This is called dimerization and can be the following: Dimerization - ANSWERS-1. Homodimerization: binding with the same type of receptor, such as an epidermal GF receptor (EGFR) 1 receptor with another EGFR
- Heterodimerization: binding with a different kind of receptor, such as EGFR1 binding with EGFR Protein tyrosine kinases phosphorylates - ANSWERS--turned on by giving up a phosphate molecule
- the message is now send via a "bucket bridage", or passing the message from one molecule to other signaling molecules until the message gets first into the cell nucleus
- where it is transcribed Pathways - ANSWERS-many pathways and crossalks signaling btw and among the different pathways, and they all have the power to control cell behavior in one way or another mitogen-activating protein kinase (Raf-1/MAPK) pathway - ANSWERS--shown to decrease the benefits of some cancer drugs
- decrease disease-free survival time in some pts
Oral Chemotherapy - ANSWERS--greater challenge to adherence because the responsibility falls on the pt and caregiver Nonadherence - ANSWERS--pt takes too few or too many pills Overadherence - ANSWERS--when a pt believes a dose was missed or that "more is better", too much medication may be taken, leading to increased toxicity Factor affecting adherence - ANSWERS--provider relationship
- side effects
- necessity
- routinization
- support
- lifestyle fit
- cost
- medication knowledge
- pill burden
- regiment complexity Lesson 2: Alkylating Agents - ANSWERS- Alkylating Agents - ANSWERS--function by causing a break in the DNA helix strand, causing interference with DNA replication, which results in cell death Alkylating Agent Subgroups - ANSWERS--Nitrogen mustards (cyclophosphamide{Cytoxin}, ifosfamide{Ifex}, bendamustine{Treanda})
- Platinum-based (cisplatin{Planitol}, carboplatin{Paraplatin}): do not possess an alkyl group
- nitrosoureas
Cisplatin (Platinol) - ANSWERS-BLACK BOX WARNING
- severe nephrotoxicity
- myleosupression Nitrosoureas - ANSWERS--subgroup of alkylating agents
- able to cross the blood-brain barrier (effective in treating some brain tumors, melanomas, lymphomas)
- Carmustine (BiCNU)
- Lomustine (CeeNu)
- Streptozocin (Zanosar)
- pulmonary monitoring recommended Carboplatin (Paraplatin) - ANSWERS--Alkylazing agent
- possibility for a hypersensitivity reaction which is rash, urticaria, erythema, pruritis, rarely bronchospasm and hypotensision
- notify RN if itching, scratchy throat, difficulty breathing, rash
- Blood count, particularly platelets, monitored because thrombocytopenia is a dose-limiting toxicity
- Oral dosage: 1-5mg/kg/day Cisplatin (Planitol) - ANSWERS--Alkylating agent
avoid exposure to cold air and consuming cold fluids for 3-4 days following treatment. Key Points to Remember about Alkylating agents and nitrosoureas - ANSWERS-- Hypersensitivity may occur with late doses of carboplatin.
- Tumor lysis syndrome is possible in patients receiving alkylating agents, particularly when there is a high tumor burden.
- Preadministration blood tests should include blood urea nitrogen, creatinine, and a complete blood count with differential.
- These agents are typically highly emetogenic. You will learn more about these implications later in this course, but take note that these drugs are typically categorized as "highly emetogenic."
- streptozocin and semustine are the most nephrotoxic drugs, affecting more than 75% of pts
- Pruritus and itching can occur with patients receiving alkylating agents and nitrosoureas.This may worsen with dehydration, so patients are encouraged to drink at least 8-10 glasses of fluid per day, in addition to minimizing salt and alcohol intake.
- Alkylating agents and nitrosoureas have the potential to cause secondary malignancies and fertility issues. Long-Term Side effects of Nitrosoureas - ANSWERS-- Alkylating agents, including nitrosoureas, can produce dose-related myelosuppression. In some rare cases, long-term myelosuppression can lead to the development of a secondary malignancy 5 - 10 years after treatment
- Short-term side effects of nitrosoureas, particularly carmustine and lomustine, include kidney disease
- However, streptozocin and semustine are the most nephrotoxic drugs, affecting more than 75% of patients
- Some specific long-term side effects of carmustine and lomustine include the following: >> Reduction of pulmonary function: Delayed pulmonary fibrosis has been seen up to 17 vears after treatment with nitrosoureas in patients who received treatment in their childhood or early adolescence >> Fatal cases of pulmonary toxicity: Baseline pulmonary function tests should be performed prior to treatment alkylating agent to the patient/caregiver education related to side effects of the agent - ANSWERS-- Steroids: Osteoporosis
- Anthracyclines: Cardiomyopathy
- Bleomycin: Pulm Fibrosis
- Liver function tests at baseline: Cirrhosis
- Vocational assessment/assistance: Executive function deficit
- Cyclophos: Hemorrhagic Cystitis
- tanner staging: growth hormone deficiency Lesson 3: Antimetabolites - ANSWERS--azacitidine
- capacitabine
- 5 - fluorouracil
- cytarabine
- decitabine
- methotrexate inhibit DNA and RNA synthesis - can cause myelosuppression, GI toxicities, phospotsensitiivty, hand foot syndrome, vigorous I V hydration to prevent tumor lysis 5 - FU - ANSWERS-- advise women of reproductive potential to use effective contraception during treatment and for up to 3 months following treatment
- any combination therapy with 5-fu will increase its toxic effects
- this drug has a narrow margin of safety
- EXTREME CAUTION: 72 y/o pt with mets colon cancer and poor renal clearance Lesson 4 - ANSWERS- Intrathecal Chemotherapy - ANSWERS--injects chemo directly into the subarachnoid space so it reaches the CNS
- Often used to treat leukemia and lymphoma that has spread to the CNS since most IV chemo does not cross the blood-brain barrier
- avoid activities that cause unnecessary force or friction on the hands or feet, such as running or aerobics
- avoid contact with harsh chemicals used in detergents and household cleaning products
- avoid activities that require you to press your hand against a hard surface
- elevate your hands and feet when sitting or lying down
- gently apply skin care creams to keep hands moist
- wear loose-fitting, well ventilated shoes Nadir - ANSWERS--point at which blood cell counts are at their lowest following treatment
- typically, but not always, occurs 7-10 days after the cycle is administered Neutropenia - ANSWERS--ANC of less than 500/mm3 or
- less than 1000/mm3 with the expectation that the count will drop below 500 in the next 48 hours Neutopenia RF - ANSWERS--older than 65
- hx of neutropenia with previous chemo
- previous chemo or radiation
- hematologic malignancy, uncontrolled or advanced cancer, or lung cancer
Neutropenic Fever - ANSWERS--temp of 38.3 or greater one time
- temp of 38 lasting 1 hour Absolute Neutrophil Count - ANSWERS-- (%segs + %bands) x (WBC) / 100 Mucositis - ANSWERS--inflammation of the mucous membrane lining the digestive tract from mouth to anus
- affects 40-100% of pts Stomatitis - ANSWERS--specifically inflammatory conditions of the mouth Xerostomia - ANSWERS--dryness of the mouth caused by damage to or dysfunction of the salivary glands Hypersensitivity Reaction (HSR) - ANSWERS--body mounts an immunologic response to a foreign substance or antigen, resulting in local tissue injury IgE-mediated - ANSWERS--immediate (within 5 minute) HSR, present like classic allergic reactions T-Cell--Mediated - ANSWERS--Delayed hypersensitivity reactions, can occur any time after the immediate hypersensitivity window, even days or weeks Type 1 HSR early S/SX - ANSWERS--pruritus
- restlessness, agitation, anxiety, feeling of impending doom
- fever, flushing, chills
- urticaria (hives)
- maculopapular rash
- edema of hands, face, and feet
