Flashcards in 28 - Oncology 2 Deck (52)
Loading flashcards...
1
Q
Define adjuvant therapy
A
Systemically administered therapy w/ cytotoxic drugs, hormones, or biologic response modifiers to kill micrometastases after the primary tumour has been eliminated (ex: chemotherapy after surgery to remove the tumour)
2
Q
Define neo-adjuvant therapy
A
Tx given before surgery to reduce tumour and allow better surgical resection
3
Q
Define remission
A
- Complete disappearance of cancer sx, typically occurring when the number of cancer cells decrease below 109
- Complete remission isn’t the same as being cured
4
Q
Define cure
A
To be rendered clinically and pathologically free of disease, and returned to a life expectancy the same as that of a healthy individual of the same age and sex
5
Q
Factors that determine tx modality
A
- Cancer type
- Location and size of tumour
- Extent of disease
- Radiosensitivity or chemosensitivity
- Hx of prior therapy
- Concurrent organ dysfunction
- Performance status (overall physical functioning)
- Px goals/wishes
6
Q
Cancer tx modalities
A
- Surgery
- Radiation therapy
- Chemotherapy
- Biological and targeted therapy
- Immune therapy
- Supportive care
7
Q
Describe surgery as a cancer tx
A
- Essential for diagnosis of cancer and for staging of many solid tumours
- Some of the role’s surgery can play in cancer management:
- Curative tx for localized mass
- Reduce size of the tumour
- Remove isolated metastatic disease
- Treat complications (ex: obstruction, hemorrhage, or perforation)
- Reconstruct anatomic defects to improve function or appearance
8
Q
Describe radiation therapy as a cancer tx
A
- Breaks bonds in DNA causing loss of proliferative capacity
- Induces apoptosis
- Plan to deliver tumoricidal dose w/in limits of tolerance of surrounding normal tissues
- Normal tissues are usually able to recover better than cancer cells
- Methods of delivery:
- External beam (teletherapy)
- Internal (brachytherapy) -> high dose rate w/ remote leading, or low dose rate implanted (temporary or permanent, ex: prostate seeds)
9
Q
Common radiation SE
A
- General = radiodermatitis, fatigue, weight loss due to anorexia
- Site-specific
- Myelosuppression (skull, sternum, long bones)
- Radiation pneumonitis/ pulmonary fibrosis
- Reproductive system
10
Q
Basic skin care highlights for post-radiation
A
- Bathing is OK unless open areas; no scrubbing of skin, pay dry
- Deodorants and antiperspirants OK unless skin reaction
- No talc, baby powder, or cornstarch in tx area
- No tape, perfume, alcohol, or jewelry in tx area
- Avoid ice packs or heating pads
- No tanning lamps, petroleum products, or shaving
- Don’t apply moisturizers w/in 2 h of tx
- Avoid sun on tx area
11
Q
What is chemotherapy? Goal?
A
- The use of cytotoxic medications to kill cancer cells
- Goal = reduce and/or eliminate visible and invisible (micrometastases) disease
- Cancer cells can develop resistance to chemotherapy
- Most often is systemic, therefore produces systemic SE
12
Q
Principles of chemotherapy
A
- Start therapy when tumour burden is low and growth fraction is high
- Use a combination of drugs
- Use a dosing schedule that limits tumour regrowth during host tissue recovery
- Dose to maximum tumour response or toxicity before changing therapy
- Therapeutic benefit must exceed toxicity
13
Q
Chemotherapy routes of administration
A
- Oral – increasingly common
- IV – bolus over mins/hrs and/or CIVI over days
- Intra-thecal – b/c most chemo doesn’t cross BBB
- *Only certain drugs are ok via this route; all other drugs are fatal
- IM – L-asparaginase
- Intra-cavitary – ex: bladder
- SC – may be used for basal cell skin cancer
14
Q
Principles of combination chemotherapy regimens
A
- Drugs are active against the tumour when used alone
- Drugs that have a biochemical basis for suspected synergy
- Drugs that have different mechanisms of action
- Drugs that produce toxicity in different organ system (or in the case of bone marrow toxicity, the toxicity occurs at different times following administration)
- Optimal dose and schedule for the agents are used
15
Q
Chemotherapy tx plan
A
- Most often given in combination according to specific research-based protocols
- Combos are usually identified by acronyms:
- R-CHOP (rituximab, cyclophosphamide, hydroxydaunorubicin, oncovin, prednisone)
- ESHAP, FEC, FolFOX
- Px are often part of clinical trials
- Doses carefully calculated according to body surface area
16
Q
Classification of chemotherapy agents
A
- Alkylating agents
- Antimicrotubule agents
- Antimetabolites
- Antitumour antibiotics
- Nitrosureas
- Corticosteroids
- Hormones
17
Q
Alkylating agents – how do they work? Cell cycle specific or non-specific?
A
- Contain highly reactive ions on their chemical structure
- In some cases, must be activated/ converted in the body to create the highly reactive, positively charged ions
- These positively charged ions react w/ electron-rich portions of the cell (proteins & DNA) to form strong chemical bonds thus leading to inhibition of DNA synthesis
- Cell cycle non-specific
18
Q
Cisplatin – toxicity, role
A
- Dose limiting toxicity = nephrotoxicity
- One of the most emetogenic antineoplastics
- Can display delayed N/V
- Other toxicities = myelosuppression, neuropathy, alopecia, and permanent ototoxicity
- Has a role as radiation sensitizer
- Very important agent used for the tx of testicular cancer, lung cancer, head and neck, breast cancer
19
Q
What is the main difference between carboplatin and cisplatin?
A
Carboplatin has more toxicities than cisplatin; main toxicity is to platelets
20
Q
Antimicrotubule agents – MOA and cell cycle specific or non-specific?
A
- Usually block a particular enzyme, or arrest the cell in some step of mitosis or cell division
- Cell-cycle specific
21
Q
Plant alkaloids – vincristine (cell cycle specificity, toxicity)
A
- Vinca alkaloid
- Cell-cycle specific inhibition of microtubule formation
- Dose limiting toxicity = peripheral neuropathy
- Other toxicities = constipation, extravasation
- Inadvertent intrathecal administration is usually fatal
22
Q
Antimetabolites – MOA, subgroups, cell cycle specificity
A
- Act by interfering w/ the metabolic processes of the cell
- Interfere w/ nucleic acid biosynthesis
- Subdivided into folate antagonists, purine analogues, and pyrimidine analogues
- As a class, tend to bind enzymes responsible for DNA or RNA synthesis
- Additionally, may mimic one of the DNA or RNA nucleotides thus halting further replication
- Cell-cycle specific
23
Q
Fluorouracil – MOA, role
A
- Most extensively studied and used agent in colorectal cancer
- Interferes w/ RNA synthesis and function
- Blocks the enzyme, thymidylate synthase
- Pattern of fluorouracil toxicity differs between bolus administration and continuous infusion
- Useful as a radiation sensitizer
24
Q
Antitumour antibiotics
A
- Act by binding to or complexing w/ DNA and/or RNA, thus inhibiting replication
- Can also produce single-strand and double-strand DNA breaks
- Can generate free radicals that will then seek out electron rich molecules such as DNA, RNA, or proteins
- Cell-cycle non-specific
25
Q
Doxorubicin (antitumour antibiotic) – use, AE
A
- Anthracycline antibiotic w/ a lifetime cumulative dosage (500-550 mg/m2)
- Most serious dose limiting SE = cardiomyopathy
- Extensive use for tx of breast cancer and lymphomas
- Can produce radiation recall (develop a rash in the place they previously had radiation)
26
Q
Bleomycin (antitumour antibiotic)
A
- Damage DNA and prevent repair
- Dose-limiting toxicity = pulmonary fibrosis
- Active agent for tx of lymphomas, testicular cancer
- Development of chills/fever post-tx
- Cell cycle specific
27
Q
What is tumour lysis syndrome?
A
- Tumour cells undergoing cancer therapy release phosphates, calcium, potassium, nucleic acids, and lactates
- This results in hyperphosphatemia/ hypocalcaemia, hyperkalemia, hyperuricemia, and acidosis
- This can result in acute kidney injury
- More common in some tumours; depends on how large tumours are and how spread out they are
- A concern in those w/ lymphomas or leukemias
- Sometimes choose chemotherapy that is milder or radiation to shrink the tumour then do the primary chemotherapy to lessen this syndrome
- Can also use allopurinol for prevention
28
Q
Chemotherapy – acute reactions
A
- Vomiting -> prevent w/ anti-emetics
- Allergic reactions -> some drugs require pre-medication to decrease risk of allergic rx/ anaphylaxis
29
Q
Chemotherapy – delayed effects
A
- N/V (especially w/ cisplatin; causes both acute and delayed N/V)
- Mucositis of varying severity, diarrhea
- Alopecia
- Bone marrow suppression; bleeding due to decreased platelets
- Fatigue due to decreased Hgb and other factors
- Skin changes -> dryness, flaking, peeling
30
Q
Major chemotherapy factors predicting risk for acute chemotherapy induced N/V
A
- Intrinsic emetogenicity of chemotherapeutic agent
- Dose, route of administration
- Rate of infusion
- Repeated cycles of chemotherapy
31
Q
Major pt factors predicting risk for acute chemotherapy induced N/V
A
- Pt characteristics (low alcohol consumption, < 50 y/o, female, hx of motion sicknes)
- Poor control w/ prior chemotherapy
32
Q
Major chemotherapy factors predicting risk for delayed chemotherapy induced N/V
A
Not well characterized in many chemotherapeutic agents
33
Q
Major pt factors predicting risk for delayed chemotherapy induced N/V
A
- Pt characteristics (low alcohol consumption, < 50 y/o, female, hx of motion sicknes)
- Poor control of acute chemotherapy induced N/V (**most important factor)
34
Q
Which drugs can be used as anti-nauseants?
A
- Steroids (dexamethasone)
- Serotonin antagonists (ondansetron)
- Dopamine receptor agents (haloperidol, domperidone, metoclopramide)
- BZDs (lorazepam) -> used for px w/ anticipatory N/V
- Neurokinin-1 blockers (aprepitant)
- Cannabinoids (nabilone, dronabinol)
35
Q
Effects of bleomycin, doxorubicin, mitoxantrone, MTX
A
Mucositis
36
Q
Effects of cytarabine, 5-FU
A
Mucositis, diarrhea
37
Q
Effects of high dose melphalan
A
Esophagitis, stomatitis, diarrhea, colitis
38
Q
Effects of high dose etoposide
A
Oropharyngeal mucositis
39
Q
Hematopoeitic therapy
A
- Granulocyte colony-stimulating factor (GCSF)
- Stimulates production, maturation, regulation, and activation of WBC
- Hastens recovery from bone marrow depression post-chemo
- Stimulates stem cell mobilization to periphery for transplant
- Very important part of many protocols
- Supportive care, not cancer tx
- Erythropoeitin -> used more commonly w/ renal disease than cancer
- Transfusions of RBCs and platelets are used instead of growth factors
40
Q
Cardiac toxicity w/ antineoplastics
A
- Known dose limiting toxicity of several agents
- Common w/ anthracycline antibiotics (ex: doxorubicin, epirubicin, daunorubicin, idarubucin, mitoxantrone)
- Seen w/ some of the MAbs
- Risk factors for cardiac damage = age, pre-existing heart disease, concurrent tx w/ cyclophosphamide, tx schedule
41
Q
Peripheral neurotoxicity w/ antineoplastics
A
- Common dose-limiting toxicity of many of the plant alkaloid agents
- Many times, the damage appears to be dose dependent, and occasionally irreversible
- Nerves that are affected are primarily the peripheral nerves, although cranial nerves and autonomic nerves can also be damaged
42
Q
Pulmonary toxicity w/ antineoplastics
A
- Rare but often fatal complication of cancer chemotherapy
- Usually a result of inflammation and subsequence formation of scars in the lungs after administration of certain chemo drugs
- Sometimes referred to as pneumonitis or pulmonary fibrosis
- Dose limiting toxicity of agents such as bleomycin, busufan, carmustine
- Concern if pt is to receive chest irradiation
43
Q
Late effects of chemotherapy
A
- Risk for leukemias and other secondary malignancies
- Radiation and chemotherapy can induce DNA damage that can lead to new malignancies other than original disease
- Secondary malignancies other than leukemia also possible
- Includes breast (especially women who had chest radiation w/o shielding prior to 1980’s), uterine, thyroid, lung
- Secondary malignancies usually tx resistant
44
Q
What is “targeted tx” for cancer? What are some examples?
A
- “Drugs or substances that block the growth and spread of cancer by interfering w/ specific molecules involved in tumour growth and progression”
- Tyrosine kinase inhibitors -> imatinib (chronic myelogenous leukemia/CML), erlotinib (NSCLC), dasatinib and nilotinib (CML)
45
Q
Biological tx for cancer; what is it and which products are approved
A
- “Uses living organisms, substances derived from living organisms, or synthetic version of such substances to treat cancer”
- Approved = MAb, cytokines
46
Q
Describe the steps to produce a protein (for a MAb)
A
- Gene from a desired protein is combined w/ a DNA sequence
- Recombinant DNA sequence is inserted into a host cell
- Host cell is grown in culture to reproduce the desired protein
47
Q
Describe biosimilars
A
- Impossible to produce a “generic” of a biologic b/c must have the exact same manufacturing process to be considered the same
- Enter the market subsequence to an innovator version previously authorized in Canada
- Have demonstrated similarity to the reference biologic
- Are highly similar but not identical; any difference in product attributes should have no adverse impact on safety and efficacy
- Biosimilars don’t have to go through phase 3 trials
48
Q
Monoclonal antibodies for cancer
A
- Engineered to bind to specific targets on cell surface
- Rituximab -> targets CD20 on surface of normal & cancer cells
- Zevalin -> also targets CD20; has a radio isotope attached to the MAb that gives off radiation when it binds to the cell (normal and cancer); so better killing of cancer cells, but more toxicity; used for px who don’t respond well to rituximab
- Bevacizumab -> MAb that targets VEGF receptor and inhibits angiogenesis
49
Q
Role of cytotoxic T-cells in cancer
A
- T-cells are a type of lymphocyte that play an active role in the immune response
- T-cells recognize and eliminate foreign or abnormal cells, including cancer cells
- Cancer cells are smart and also have mechanisms to evade T-cell recognition
50
Q
What are BITEs? What is an example?
A
- Bispecific T-cell engager (BiTE) Ab w/ dual specificity for CD19 and CD3
- Simultaneously binds CD3 positive cytotoxic T cells and CD19-positive B cells, resulting in T-cell mediated lysis of normal and malignant B-cells
- Engages px endogenous T cells to attack and eradicate B-precursor leukemic blasts
- Blinatumomab
51
Q
What do PD-1/ PD-L1 inhibitors do?
A
- PD-L1 ligand is present on normal tissue, causes T-cell not to target normal tissues
- Some tumours have developed the ability to overexpress the PD-L1 ligand, so it tricks the T-cell to believe it’s a normal host cell and won’t kill it
- Good for px that are resistant to all other chemotherapy drugs (considered a “salvage” therapy)
52
Q
Bicalutamide – MOA, role, and SE
A
- Useful for tx of prostate cancer
- Inhibit translocation of androgen receptor not allowing testosterone to bind
- Useful in combo w/ gonadotropin-releasing hormone analogues
- Oral medication; major SE = diarrhea
