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ONCOLOGY - TREATMENT Flashcards

1
Q

What is radiotherapy used for?

A

Primary curative oncology treatment, adjuvant therapy and palliative of cancer symptoms
It’s also, less commonly, used to treat non-malignant diseases e.g graves thyroiditis and keloid scarring

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2
Q

How does radiotherapy work?

A

Linear accelerator causes high speed particles to collide with a target inside the machine and photons are released and targeted to the patient. (Electrons and protons can be used but this is less common)
Indirect - Radiation contacts water which produces free radicals. Contact with nearby oxide produces superoxide radicals which cause damage to the cell
Direct - accumulation of double strand breaks lead to cell death.

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3
Q

Why are cancer cells more vulnerable to radiation than healthy cells?

A

They divide more often than normal thus their cell cycle repeats more frequently and they are therefore more vulnerable to damage by radiation
They also cannot repair damage as well as healthy cells

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4
Q

What is fractionation? Why is it important in radiotherapy?

A

When you distribute damage by breaking up the total dose of radiation

Important as not all cells are dividing at the same time so you need to repeat the process until all the cancer cells are destroyed
It also allows normal cells to recover in between treatment fractions (normal cells repair DNA damage better)

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5
Q

What are the different types of radiotherapy?

A

External bean radiotherapy
Brachytherapy
Internal

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6
Q

What is external beam radiotherapy?

A

The most common form of radiotherapy
An external source of ionising radiation is pointed at a particular part of the body

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7
Q

What is brachytherapy?

A

a form of radiation therapy where a sealed radiation source is placed inside or next to the area requiring treatment
Commonly used for cervix, prostate

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8
Q

What is internal radiotherapy?

A

Radiotherapy is administered orally or IV as isotopes.
E.g. oral iodine-131 therapy for thyroid cancer

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9
Q

For which cancers is radiotherapy curative on its own?

A

Prostate
Cervix
Vocal cord
Non-melanoma skin cancer

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10
Q

What is chemo radiation?

A

When they have chemotherapy at the same time as radiotherapy

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11
Q

What are the late side effects of radiotherapy?

A

Skin pigmentation changes
Pulmonary fibrosis
Infertility
Secondary cancers

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12
Q

What are radiotherapy-induced second malignancies?
What are the most common types

A

Cancer caused by previous radiotherapy
Most common cancers are AML< ALL and CML

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13
Q

What are the types of radioisotope therapy and their indications?

A

Iodine-131 for thyroid cancers
Strontium-89 and samarium-153 - metastatic bone cancer
Radium-223 for prostate cancer spread to bones

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14
Q

How long are radical radiotherapy treatments?

A

4-7 weeks

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15
Q

What are linear accelerators?

A

Machines that generate x-rays at high energies which enable administration of high doses of radiation to deep-seated tumours and minimise doses to the skin and subcutaneous tissue

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16
Q

What are the main groups of cytotoxic chemotherapy?

A

Alkylating agents
Platinum compounds
Antimetabolites
Anthracyclines
Topoisomerase inhibitors
Anti-microtubule agents
Tyrosine kinase inhibitors
Plant alkaloids aka mitotic inhibitors
Anti-tumour antibiotics

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17
Q

What are alkylating agents?

A

Anti-proliferative drugs that bind covalently with DNA via alkyl groups to form covalent bonds, causing single-strand or double- strand DNA breaks and cross-linking. This DNA is unable to complete normal cell division and so undergo cell arrest where it will be repaired or undergo apoptosis

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18
Q

What are the examples of alkylating agents?

A

Nitrosureas e.g. carmustine, lomustine, semustine, fotemustine and streptozotocin
Dacarbazine
Procarbazine
Cyclophosphamide

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19
Q

What are examples of platinum compounds used in chemotherapy?

A

Cisplatin
Carboplatin
Oxaliplatin

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20
Q

How do platinum compounds work for chemotherapy treatment?

A

Cross-link DNA strands, thereby inhibiting DNA synthesis and function. If the DNA is damaged enough, the cell will undergo apoptosis

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21
Q

What are antimetabolites?

A

Cytotoxic agents that structurally resemble naturally occurring purines and pyrimidines.

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22
Q

How do antimetabolites work for chemotherapy treatment?

A

They disrupt the pathway responsible for DNA synthesis by mimicking nucleobases or folic acid, and cause DNA replication and cell proliferation to come to a halt.

Medications that mimic purine include azathioprine and cladribine, while medications that mimic pyrimidine include cytarabine and 5-fluorouracil. Finally, there’s folic acid analogues like methotrexate.

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23
Q

Why are antimetabolites schedule dependant rather than dose dependant?

A

Because they generally act at the S phase of the cell cycle

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24
Q

What are examples of antifolates used in chemotherapy?

A

Methotrexate
Pametrexed

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25
How do antifolates work?
antagonise the actions of folic acid which primary function is as a cofactor to various methyltransferases involved in serine, methionine, thymidine and purine biosynthesis. Consequently, antifolates inhibit cell division, DNA/RNA synthesis and repair and protein synthesis.
26
What are the subtypes of antimetabolites?
Antifolates Anti pyrimidine Arabinosides Anti purines
27
What anthracyclines/anti-tumour antibiotics do we use for chemo?
Daunorubicin, doxorubicin, mitomycin and bleomycin
28
What are anthracyclines?
Drugs extracted from streptomyces species
29
How do anthracyclines work?
Intercalate with DNA causing ss and ds breaks Generation of free radicals which can cause oxidative damage to cellular proteins Topoisomerase 2 inhibition
30
What are examples of topoisomerase inhibitors used in chemo?
Topoisomerase I inhibitors include irinotecan, topotecan, and camptothecin Topoisomerase II inhibitors include etoposide, doxorubicin, and epirubicin.
31
How do topoisomerase inhibitors work?
DNA cannot unwind so DNA replication is inhibited.
32
What are examples of vinca alkaloids?
Vincristine Vindesine Vinorelbine Vinblastine
33
What are examples of taxanes?
Paclitaxel and docetaxel
34
What is tubulin?
The basic subunit of microtubules, which have many important, diverse roles in cell function including maintenance of cell shape, mitosis, meiosis, secretion, intracellular transport and axonal function.
35
How do vinca alkaloids work?
A type of antimicrotubule agent - Inhibit microtubules formation which disrupts M phase, causing cell arrest
36
How do taxanes work?
A type of antimicrotubule agent - Bind to microtubules already formed and inhibit their breakdown, which means the M phase doesnt complete and you get cell arrest
37
What are examples of tyrosine kinase inhibitors used in chemotherapy?
Imatinib - CML and GI stromal tumours Erlotinib - non-small cell lung cancer Sunitib - renal cancer Sorafenib - renal cancer Lapatinib - breast cancer
38
How do tyrosine kinase inhibitors work?
phosphorylate specific amino acids on substrate enzymes, which subsequently alter signal transduction leading to downstream changes in cellular biology
39
For which cancers are hormone therapy particularly effective for?
Breast and prostate cancer
40
Outline the difference in hormone synthesis between pre- and post-menopausal women
premenopausal women, oestradiol is primarily pro- duced from the ovaries, whereas in postmenopausal women peripheral conversion of adrenal androgens by aromatase within peripheral fat pre- dominates.
41
How is hormonal therapy achieved in men and pre-menopausal women?
Castration
42
How is hormonal therapy achieved in post-menopausal women?
SERMs and aromatise inhibitors
43
What is tamoxifen and what are its indications?
Selective oestrogen receptor modulator Pre- and perimenopausal women with oestrogen-receptor-positive breast cancer not previously treated with tamoxifen Anovulatory infertility Gynaecomastia
44
What are the main side effects of tamoxifen?
Hot flushes, night sweats and vaginal discharge Nausea, mood swings, fatigue, depression, hair thinning, constipation etc
45
What are contraindications of tamoxifen?
Increased risk of thrombotic events so should be avoided in individuals with a history of DVT or PE
46
What are examples of aromatase inhibitors? What are the indications?
Anastrazole Letrozole Exemastane Osteogenesis receptor positive breast cancer in post menopausal women
47
How do aromatise inhibitors work?
Inhibit aromatase which stops the conversion of androgens into oestradiol
48
What are the contraindications for aromatase inhibitors?
Pre-menopausal women unless ovarian suppression has been induced
49
What are the side effects of aromatase inhibitors?
Hot flushes Arthralgia Reduced bone mineral density and increased risk of fractures Alopecia
50
What hormone therapy can be used in prostate cancer?
Androgen deprivation therapy Anti-androgens e.g. bicalutamide
51
What is androgen deprivation therapy?
Therapy which reduces serum testosterone to castrate levels It can be done by surgical castration or chemical castration e.g. diethylstilboestrol
52
What are the side efefcts of androgen deprivation therapy?
Hot flushes Sweats Reduced libido Reduces muscle mass, strength and weight gain Bone mineral density loss Increased risk of fatal cardiac events
53
Whats the moa of tamoxifen?
An anti-osteogenesis which induces gonadotropin release by occupying oestrogen receptors in the hypothalamus, thereby interfering with feedback mechanisms
54
What are examples of monoclonal antibodies?
Rituximab Trastuzumab Pertuzumab Bevacizumab
55
How does methotrexate work?
Inhibits dihydrofolate reductase
56
What are the most common 2 antimetabolites?
Methotrexate and 5-fluorouracil
57
What are monoclonal antibodies?
Antibodies to a specific tumour antigen can slow tumour growth by enhancing host immunity
58
What are the most common side effects from chemo?
Hair loss Mood changes, poor concentration and fatigue (chemo brain) Taste changes Mucositis Poor appetite Nausea and vomiting And Diarrhoea constipation (often due to anti-emetics) Dry sore skin, brittle nails Loss of libido, sterility Peripheral neuropathy Bone marrow toxicity - anaemia, thrombocytopenia and neutropenia Can also cause Pulmonary toxicity, cardio toxicity or hepatotoxicity, nephrotoxicity and bladder toxicity
59
How do topoisomerase 1 inhibitors work?
Inhibits topoisomerase I which prevents relaxation of supercoiled DNA
60
What are anti microtubules agents? What are the subtypes?
Disrupt M phase of cell cycle leading to cell arrest and eventually apoptosis E.g. taxanes and vinca alkaloids
61
Why does chemotherapy cause nausea and vomiting?
Chemotherapy drugs target the CTZ in the medulla. The toxins can stimulate the CTZ because its not within the blood-brain barrier. This stimulates the vomiting centre which induces the emetic reflex
62
Why doe chemotherapy cause Alopecia?
Chemo drugs target cells with high cell turnover, as hair cells do
63
What types of systemic anti cancer drugs are there?
Cytotoxic chemotherapy Hormone therapy Targeted therapy Immunotherapy
64
What is induction chemotherapy?
The first phase of treatment where the goal is to destroy as manu cancer cells as possible in order to induce a remission
65
What is consolidation chemotherapy?
A form of post-remission therapy Drugs are given in higher doses
66
What is maintenance chemotherapy?
A form of post-remission treatment The 3rd stage where the goal is to prevent disease relapse after induction and consolidation therapy They recieve lower doses of drugs
67
What is neoadjuvant chemotherapy?
Chemo before surgery to shrink the tumour
68
What is adjuvant chemotherapy?
Chemotherapy in addition to or after the main treatment It eliminates micrometastases and reduces the risk of recurrence
69
What is combination chemotherapy?
Using chemotherapy in combination with radiotherapy. It makes cells more sensitive to radiation and increases the chances of success of treatment
70
What is minimal residual disease?
A term used to describe a very small number of cancer cells that remain in the body during or after treatment Found using flow cytomegalovirus, PCR and next-generation sequencing This helps distinguish between patients who need additional (or different) treatment from those who do no
71
What is a PICC line?
Peripherally inserted central catheter - inserted into peripheral vein and advanced up so they sit just above the RA of the heart
72
What are Hickman lines?
A central line catheter placed into a vein in the chest and the tip sits just above the RA
73
What is a portacath?
a small medical appliance that is installed beneath the skin. A catheter connects the port to a vein
74
What are examples of drugs that work in the S phase of the cell cycle?
Antimetabolites
75
What are examples of drugs that work in the G2 phase of the cell cycle?
Bleomycin Topoisomerase 1 inhibitors
76
What are examples of drugs that work in the M phase of the cell cycle?
Taxanes and vinca alkaloids
77
What are examples of non-specific chemotherapy drugs?
Alkylating agents Platinum agents Nitrosureas
78
Why is chemotherapy given in cycles?
Because chemo kills a fraction of the cancer cells It is not number specific Cycles allow the highest tolerable dose to kill the highest possible fraction of cells without causing intolerable side effects with the shortest interval possible to prevent re growth of the tumour but still allowing enough time for the bone marrow to recover
79
Outline multi-drug resistant to chemotherapy?
Cancer cells have mutations which allow the formation of efflux pumps which can pump cytotoxic drugs out of the cell even if they have never been exposed to them before It can also be caused by elevated metabolism of xenobiotics, growth factors, increased DNA repair and genetic factors MDR is responsible for over 90% of deaths in cancer patients
80
Why is combination chemotherapy more successful?
You give drugs that are effective against the tumour type, have different MOAs which act on different parts of the cell cycle, not susceptible to the same mechanisms of resistance and have different g side effect profiles This overcomes cell cycle specification, toxicity and drug resistance
81
What are the main adverse effects of Cisplatin?
Ototoxicity, peripheral neuropathy, hypomagnesaemia
82
Whats the moa of cyclophosphamide?
It’s an alkylating agent i.e. it causes cross-linking in DNA
83
What are the adverse effects of cyclophosphamide?
Haemorrhagic cystitis Myelosuppression Transitional cell carcinoma
84
Whats the moa of bleomycin?
It’s a cytotoxic antibody i.e. it inhibits DNA synthesis
85
Whats the main adverse effect of bleomycin?
Lung fibrosis
86
Whats the moa of doxorubicin?
It’s a cytotoxic antibiotic but an anthracycline - it stabilises DNA-topoisomerase II complex which inhibits DNA and RNA synthesis
87
Whats the main adverse effect of anthracyclines?
Cardiomyopathy
88
Whats the moa of methotrexate?
Inhibits dihydrogolate reductase ans thymidylate synthesis
89
What are the main adverse effects of methotrexate?
Myelosuppression Mucositis Lung fibrosis Liver fibrosis
90
Whats the moa of fluorouracil?
It’s a pyrimidine analogue that induces cell cycle arrest and apoptosis by blocking thymidylate synthase (therefore works during S phase)
91
What are the main SE of fluorouracil?
Myelosuppression Mucositis Dermatitis
92
Whats the moa of 6-mercaptopurine?
It’s a purine analogue that decreases purine synthesis
93
Whats the main adverse effect of 6-mercaptopurine?
Myelosuppression
94
Whats the moa of cytarabine?
Pyrimidine antagonist that interferes with DNA synthesis specifically at the S-phase of the cell cycle and inhibits DNA polymerase
95
What are the main SE of cytarabine?
Myelosuppression Ataxia
96
Whats the moa of vinblastine and vincristine?
Inhibits the formation of microtubules
97
Whats the main SE of vincristine and vinblastine?
Vincristine - peripheral neuropathy and paralytic ileus Vinblastine - myelosuppression
98
Whats the moa of docetaxel?
Prevents microtubule depolymerisation and disassembly, decreasing free tubulin
99
Whats the main SE of docetaxel?
Neutropenia
100
Whats the moa of irinotecan?
It inhibits topoisomerase 1 which prevents relaxation of supercooled DNA
101
What are the main SE of Cisplatin?
Ototoxicity Peripheral neuropathy Hypomagnesaemia
102
Whats the moa of hydroxycarbamide?
Aka hydroxyurea It inhibit ribonucleotide reductase, decreasing DNA synthesis
103
What are the early side effects of radiotherapy?
Fatigue Mucositis Skin erythema Alopecia
104
Which chemo drugs cause cardiomyopathy?
Anthracyclines - doxorubicin, daunorubicin

METABOLIC (43 decks)

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