Chemotherapy COPY COPY

Question 1

What are the different types of treatment available for cancer

Answer 1

Surgery
Radiotherapy
Chemotherapy 
Targeted therapies
Immunotherapy

Question 2

What types of chemotherapy are there

Answer 2

IV or oral for systemic delivery/absorption

Question 3

How should systemtic therapy be delivered

Answer 3

Oral or intravenous route
Regular cycles with timing dependent on the findings from pharmacokinetics (half life, excretion)
May be need for delay if toxicities develop
Intensification previously evaluated: better in non-solid tumours

Question 4

What methods can be used to access drug activtiy

Answer 4

Objective
Improved
Adjuvant
Neoadjuvant

Question 5

Describe the objective method

Answer 5

It shows an objective response in advanced disease via CT scan, PET scan and/or clinical examination
RECIST criteria if radiological

Question 6

Describe the improved method

Answer 6

Shows:
Overall survival (OS)
Progression-free survival (PFS)
Improved quality of life (QoL)

Question 7

Describe the adjuvant method

Answer 7

Shows if treatment improves survival

Question 8

Describe the neoadjuvant method

Answer 8

It may improve survival through increasing operability or reduce the ‘filed’ of radical radiotherapy (treatment before surgery)

Question 9

Name the catergories that cytotoxic agents be classified into

Answer 9

Alkylating agents
Anti-metabolites
Mitotic inhibitors
Antibiotics
Others

Question 10

What is the site of action for anti-metabolites

Answer 10

DNA synthesis

They impair replication

Question 11

What is the site of action for alkylating agents

Answer 11

DNA

Question 12

What is the site of action for intercalating agents

Answer 12

DNA transcription

DNA duplication

Question 13

What is the site of action for spindle poisons

Answer 13

Mitosis

Question 14

What is the mode of action for alkylating agents

Answer 14

The alkyl group allows covalent bonds with other molecules
DNA helix X-links intra- and interstrand
Attaches to free guanines at N6 on separated DNA strands
Can not act as templates for new DNA formation

Question 15

What is the structure of antimetabolites

Answer 15

Similar chemical structure to essential metabolites required by cell prior to cell division

Question 16

What is the mode of action for antimetabolites

Answer 16

They may be incorporated into new nuclear material or bind irreversibly with vital enzymes to inhibit cell division

Question 17

Give examples of antimetabolites

Answer 17

Antagonise folic acid (methotrexate)
Antagonise purine (6-mercaptopurine, 6-thioguanine)

Question 18

What is the mode of action for vinca alkaloids

Answer 18

They bind to tubulin and block microtubule formation and spindle formation which is essential for metaphase of mitosis)

Question 19

What are vinca alkaloids

Answer 19

They are metaphase arrest agents

Question 20

What is the mode of action for taxanes

Answer 20

They promote spindles and ‘freeze’ cells at that stage of cycles

Question 21

Name the categories of antimitotic antibiotics

Answer 21

Anthracyclines

Non-anthracyclines

Question 22

Describe the features of antimitotic antibioditics

Answer 22

They intercalate and inhibit DNA and RNA synthesis
Membrane binding and increase permeability to various ions
Free radicals disrupt DNA chain and prevent mitosis
Metal ion chelation resulting in cytotoxic compounds
Alylation blocking DNA replication

Question 23

At what stage of the cell cycle do antibiotics work

Answer 23

End of G1
S
Beginning of G2

Question 24

At what stage of the cell cycle do antimetabolites work

Answer 24

S phase

Question 25

At what stage of the cell cycle do vincaalcaloids work

Answer 25

Beginning of M phase

Question 26

At what stage of the cell cycle do mitotic inhibitors work

Answer 26

M phase

Question 27

At what stage of the cell cycle do taxoids work

Answer 27

End of M | Beginning of G1

Question 28

At what stage of the cell cycle do alkylating agents work

Answer 28

The whole cell cycle | G1, S, G2, M

Question 29

What is the aim of combination therapy

Answer 29

To increase efficacy

Question 30

What does combination therapy combine

Answer 30

Different mechanisms of action | Different mechanisms of resistances

Question 31

What are the principles of combination chemotherapy

Answer 31

To combine those with: Different mechanism of actions Dissimilar toxicity profile e.g. not both with neurotoxicity (cisplatin and taxane)

Question 32

What should the different mechanisms of action have

Answer 32

Synergistic or additive effect | Reduce risk of developing resistance

Question 33

How should the drugs given in combination therapy be given

Answer 33

Both given to maximum tolerated dose

Question 34

What are the possible side effects of chemotherapy (at least 5)

Answer 34

``` Alopecia Mucositis Plumonary fibrosis Cardiotoxicity Nausea/vomiting Local reaction Renal failure Diarrhoea Cystisis Sterility Myalgia Myelosupression Nueropathy Phlebitis ```

Question 35

What were the most distressing side-effect of chemotherapy in 1983

Answer 35

``` Vomiting Nausea Alopecia Thought of coming for treatment Length of time treatment takes at the clinic Having to have an injection Shortness of breath Constantly tired Difficulty sleeping Affects family or partner ```

Question 36

Side effects of chemotherapy can be...

Answer 36

Managed and/or prevented

Question 37

Modern chemotherapy drugs are...

Answer 37

More tolerable

Question 38

What other cancer systemic therapies are there

Answer 38

Hormonal | Targeted

Question 39

Name some hormonal drugs used

Answer 39

Anti-oestrogen - tamoxifen, aromatase inhibitors Gonadorelin analogue e.g. Goseralin (Zoladex) Anti-androgen - CPA, flutamide

Question 40

Name some targeted drugs used

Answer 40

Gefitinib/Erlotinib for EGFR | Bevacizumab (Avastin) for VEGF

Question 41

Name some immunotherapy drugs

Answer 41

Nivolumab, Pembrolizumab, Atezolizumab, Durvalumab, Avelumab which are all PD-1 or PD-L1 inhibitors

Question 42

What combination immunotherapy has been approved for melanoma

Answer 42

Ipilimumab | Nivolumab

Question 43

What side effects can occur from immunotherapy

Answer 43

Immune mediated (e.g. colitis, pneumonitis, endocrinopathies)

Question 44

In combination therapy what should be considered when choosing drugs

Answer 44

Drugs with similar side effects/toxicities should not be combined together