Cancer Care Treatment Flashcards
What are the classifications of anticancer drugs?
- Alkylating agents
- Antimetabolites
- mitotic inhibitors
- antibiotics
- Nitrosoureas
- antibody
- enzyme
- DNA synthesis inhibitors
- Signal transduction inhibitor
- Differentiation agent:
- Hormones and hormone antagonists:
- Proteasome inhibitors:
- DNA topoisomerase I inhibitors
- Agents that inhibit DNA repair
- Arsenic trioxide
- Inhibitors of DNA methylation
- Chimeric toxic protein:
classifications of anticancer drugs: examples of alkylating agents
cyclophosphamide
chlorambucil
mechlorethamine
melphalan
classifications of anticancer drugs: examples of antimetabolite agents
methotrexate
pemetrexed (Alimta), 6-mercaptopurine, 5-fluorouracil, capecitabine, cytosine arabinoside, gemcytabine
classifications of anticancer drugs: examples of mitotic inhibitors
vinblastine, vincristine, paclitaxel (Taxol), docetaxel (Taxotere)
classifications of anticancer drugs: examples of antibiotics
actinomycin D, doxorubicin (Adriamycin), daunomycin, bleomycin
classifications of anticancer drugs: examples of Nitrosoureas
carmustine (BCNU), lomustine (CCNU)
classifications of anticancer drugs: examples of antobodies
trastazumab (Herceptin), bevacizumab (Avastin),
cetuximab (Erbitux), rituximab (Rituxan)
classifications of anticancer drugs: examples of enzymes
asparaginase
classifications of anticancer drugs: examples of Agents that inhibit DNA synthesis
hydroxyurea
classifications of anticancer drugs: examples of agents that damage DNA
cisplatin, carboplatin, oxaliplatin
Chemotherapy: Mechanisms of Drug Resistance
- The cell membrane is impermeable
- The drug is actively pumped out of the cell by the Pglycoprotein
- The drug is not metabolized to an active form
- The drug is inactivated
- The drug target is increased e.g. increased level of
enzyme or gene amplification - Mutation in a target protein decreases the affinity for
the drug - Alternative biochemical pathways are increased
- There is a decrease in topoisomerase II and DNA
breaks - DNA damage is repaired
Chemotherapy: How do alkylating agents work?
The alkylating agents either spontaneously or after metabolism yield an unstable alkyl group, R-CH2+, which reacts with nucleophilic centers on proteins and nucleic acids. In most cases they may be considered to be cell
cycle nonspecific agents. Many are bifunctional and can cross-link two DNA chains.
What are the principles of immunotherapy?
Immunotherapy is a treatment that uses the body’s own natural defenses to fight cancer. White blood cells (T cells) that make up the immune system can be stimulated in several ways by specially designed drugs that allow them to recognize and kill cancer cells.
Early immunotherapy drugs worked in a general way by boosting the body’s immune system to fight cancer cells. However, recent research has discovered several proteins on the surface of T cells that act like a brake, or checkpoint, preventing them from attacking cancer cells.
Immunotherapy: how do checkpoint inhibitors work?
- CTLA-4 (1996): Ipilimumab, an immune checkpoint inhibitor that turns off CTLA-4 and allows the T cells to do their work..
- PD-1 (2000) Several drugs have been developed to turn off PD-1 in many types of cancer, allowing existing T cells near the tumor to attack.
Targeted immunotherapies principles
- Targeted immunotherapies attack specific proteins on the surface of cells that help identify cancer and stimulate an immune response.
- Monoclonal antibodies are designed to identify specific abnormalities on the surface of cancer cells.
The 3 “E”s of immuno-editing of cancer
• Elimination • Equilibrium • Escape
Describe Equilibrium in immuno-editing of cancer
- Escaping tumor cells persist in a delicate balance of growth and immune suppression.
- Immune system is able to keep tumor cells from growing out of control, but unable to eliminate them completely.
- During this phase tumors develop new adaptations to evade the immune system
Describe Escape in immuno-editing of cancer
- Tumors adaptations to disrupt equilibrium and suppress the immune system.
- A common method is to manipulate checkpoint pathways, which act as natural “brakes” for an immune response.
What mechanisms are used by tumours to evade the immune system?
• Hypoxia in tumors induces HIF-1SDF-1, a chemokine to attract MDSCs and TAM to the tumor microenvironment through the receptor CXCR4.
• Down regulate MHC-I
• Myeloid-derived suppressor cells (MDSCs ) and tumor-associated macrophages (TAMs), they can
• induce Tregs, and directly inhibit CTLs.
• secrete cytokines such as IL-10 that promote a regulator phenotype among intratumoral DC
• express PD-L1 and PD-L2, which inhibit CTL function through the PD-1 receptor
• TGF-b
• reactive oxygen species (ROS)
• reactive nitrogen intermediates (RNI)
• arginase and nitricoxide synthase (NOS),
deplete l-arginine, an important metabolite for CTL function.
Current immunotherapies used for lung cancer
- monoclonalantibodies • therapeuticvaccines
- adoptivecelltherapy
- checkpoint inhibitors
Summarise chemotherapy
• Normally, cells live, grow and die in a predictable way.
• Cancer occurs when certain cells in the body keep dividing and
• •
forming more cells without the ability to stop this process.
Chemotherapy involve destroying cancer cells by keeping the cells from further multiplying.
Chemotherapy is toxic to all cells–including those that are perfectly healthy. While relatively effective, this can lead to unpleasant side-effects
Side effects of chemotherapy
Alopecia
Pulmonary fibrosis Cardiotoxicity Local reaction Renal failure Myelosuppression Phlebitis
Mucositis
Nausea/vomiting
Diarrhea/Constipation Cystitis Infertility/dysfunction Myalgia
Neuropathy
Grading of toxicity in chemotherapy
- Grade 1: minimal symptoms
* Grade 2: Requires medication • Grade 3: Needs hospitalisation • Grade 4: Life threatening
Immune related adverse reactions
- Based on the severity of the adverse reaction, pembrolizumab should be withheld and corticosteroids administered
- Upon improvement to Grade ≤ 1, corticosteroid taper should be initiated and continued over at least 1 month
- Pembrolizumab may be restarted within 12 weeks after last dose of pembrolizumab if the adverse reaction remains at Grade ≤ 1 and corticosteroid dose has been reduced to ≤ 10 mg prednisone or equivalent per day
- Based on limited data from clinical studies in patients whose immune-related adverse reactions could not be controlled with corticosteroid use, administration of other systemic immunosuppressants can be considered
Monitoring and management of Immune- related pneumonitis
Immune-related pneumonitis
• For signs and symptoms of pneumonitis
• Suspected pneumonitis should be confirmed with
radiographic imaging and other causes excluded
• • •
Administer corticosteroids for Grade ≥2 events
(initial dose of 1–2 mg/kg/day prednisone or equivalent followed by a taper)
Withhold pembrolizumab for Grade 2 pneumonitis until adverse reactions recover to Grade 0-1
Permanently discontinue pembrolizumab for Grade 3, Grade 4, or recurrent Grade 2 pneumonitis
What is Parenteral Nutrition (PN)?
PN involves the delivery of a volumetrically
controlled infusion through a venous catheter an
effective means of providing nutritional support.
The term TPN, although frequently used, is misleading and outdated. It implies the solution is nutritionally complete. In practice, not all PN solutions contain the full spectrum of macro and micronutrients, or will meet an individual’s nutritional requirements, and unless someone is nil by mouth they will be taking some nutrients orally.
When to consider Parenteral Nutrition (PN)
Consider PN if the patient has:
• Inaccessible small bowel
• Non-functioning or functioning insufficiently small bowel e.g.
short bowel
• Post operative patients on bowel ‘rest’
• Patients who are likely to be nil by mouth for 5 days or more e.g. prolonged ileus
• Severe inflammatory bowel disease
• Severe pancreatitis in whom naso jejunal feeding is not possible
• Unsuccessful enteral feeding e.g. continuous vomiting
Typical contents of PN
- PN bags used in MKUH are pre-compounded ‘standard’ bags by a pharmaceutical company
- Protein is referred to in grams of nitrogen
- Carbohydrate is provided as glucose
- Fat is provided in the form of lipid
- Fluid and electrolytes can be adjusted daily depending on the patients’ blood biochemistry and any abnormalities corrected prior to commencing PN
- Vitamins and minerals chemical stability can be affected by light and temperature, and destabilisation can be harmful, and must be stored at the correct temperature and protected from light
Who can administer PN
- Due to the risk of sepsis and metabolic complications associated with its delivery, staff are required to attend Parenteral Nutrition (PN) training and achieve a level of competency in order to be able to administer parenteral nutrition (PN)
- This is supported by the British Association of Parenteral and Enteral Nutrition (BAPEN), who recommend that continuing education programmes exist for all staff involved in the clinical care of patients receiving this therapy (Pennington 1996)
- Nurses must have completed the IV drug administration assessment training prior to completing PN training.
Administration of PN
• Initially PN is initiated as a continuous infusion (i.e., each bag over 24 hours)
• Cyclical PN (usually overnight), thought to be less harmful to the liver, and allows the patient to
be free from the infusion during the day (Thorell & Nordenstrom 2001).
• Long-term PN fed patients who are not fluid dependent do not need to receive PN every day.
Maximum hang times/changing the giving set
• Lipid containing solutions are hung for a maximum of 24 hours
• Giving-sets changed every 24 hours (DoH 2001, CDC 2002)
• There are no specific recommendations for other PN regimens but as glucose solutions enhance
microbial growth, applying these guidelines to all PN regimens seems appropriate.
Needle-less devices
Needle free access devices reduce the risks of needle-stick injury and transmission of blood borne pathogens, and can be left insitu for up to 7 days.
What Intravenous Access for PN. Advantages of central
Considered good IV practice to select smallest size catheter necessary for chosen therapy so as to have maximum blood flow around device
Central • Rapid dilution of irritant drugs • Stable access, ↓ tissue damage • Simultaneous infusion of incompatible drugs • Avoids repeated cannulations • Risk of line sepsis
Peripheral • Can start immediately • Requirements compromised with peripheral PN • Only Kabiven 7 goes peripherally (can be given centrally) • Increased risk of thrombophlebitis
Venous access considerations for PN
Short / long term use
• Elective or emergency
• Flow rate of intended therapies
– Continuous or cyclical? • Need for other IV therapies
Multi or single lumen
• Who will be inserting the device and how?
• Where? - Ultrasound/Radiology • Is the patient is self caring?
Cuffed or un-cuffed / Gauge of catheter
• Any known allergies to catheter materials
• Who will be caring for the device?
Multi-lumen CVC
• Have lumens of differing size entering the bloodstream at different points along the superior vena cava
Once a lumen has been selected for PN it should be used exclusively so as to reduce the risk of line infection
Identifying lines, midline vs PICC line
A PICC line is a catheter usually iinserted into the basilic vein in the upper arm, with the tip in the Superior Vena Cava.
A Midline is peripherally inserted into the basilic vein via the veins of the antecubital fossa or upper arm with the tip terminating in the axillary vein.
- Kabiven 7 ONLY peripheral use
CHECK the medical notes – Both line may look very similar
Risks of Central Venous Access: Air embolus clinical features.
Chest pain, dyspnoea, tachycardia, hypotension, hypoxia
Risks of Central Venous Access: Pneumothorax clinical features.
Pain on inspiration/expiration, dyspnoea
Risks of Central Venous Access: Pneumothorax clinical features.
Dyspnoea, tachycardia
Risks of Central Venous Access: Catheter malposition clinical features.
Back flow of blood, coughing, ear/neck pain, palpitations/arrhythmia’s, aspiration
Risks of Central Venous Access: Cardia arrhythmias clinical features.
If the catheter extends beyond the SVC and touches the cardiac wall
