Chemotherapy

Question 1

How long does the cell cycle last?

Answer 1

Varies from 9 to 43 hours

Question 2

Why are non-growing micro-metastases often a problem in chemotherapy?

Answer 2

It cannot target cells in G0

However can get drugs which push them out of G0

Question 3

Name some tumours that are highly sensitive to chemotherapy

Answer 3

Lymphoma
Germ cell tumours
Neuroblastoma
Wilm’s tumour

Question 4

Name some cancers which have low sensitivity to chemotherapy

Answer 4

Prostate
Renal cell
Brain tumours
Endometrial cancer

Question 5

What are the different ways tumours can spread?

Answer 5

Local
Lymphatic
Blood
Implantation

Question 6

What are the different options for using chemotherapy?

Answer 6

Primary treatment - radical, first line treatment

Adjuvant - post-operative, when at high risk of metastases after removal of the primary tumour

Neoadjuvant - primary treatment in a localised tumour, assess biological responsiveness and before surgery to reduce tumour size

Palliative - in advanced disease

Salvage - in relapsed disease

Question 7

What is the Philadelphia chromosome?

Answer 7

An oncogene where there has been a translocation of 9 to 22

Seen in chronic myeloid leukaemia

Question 8

Which chemotherapy targets the Philadelphia chromosome?

Answer 8

Imatinib

Question 9

What is the mechanism of action of imatinib?

Answer 9

Bcr-Abl tyrosine kinase inhibitor

Question 10

What is tyrosine kinase?

Answer 10

An enzyme that can phosphorylate proteins from ATP

When switched on permanently, can cause unregulated cell growth

Question 11

What is the mechanism of action of chemo drugs ending in ‘nib’?

Answer 11

Inhibit tyrosine kinase

Question 12

Why is chemo normally administered in pulses?

Answer 12

Depletes bone marrow as well as tumour cell population

Allows bone marrow cells to recover and they recover to higher level than cancer cells can in that time

Question 13

When would chemotherapy be given continuously?

Answer 13

When they need a bone marrow transplant

Question 14

Mechanism of action of antimetabolites?

Answer 14

Stop DNA synthesis

Question 15

Mechanism of action of alkylating agents?

Answer 15

Bind to DNA and fix it so that it cannot be unwound and replicated

Question 16

Mechanism of action of intercalating agents?

Answer 16

Affect DNA transcription and duplication

Question 17

Mechanism of action of spindle poisons?

Answer 17

Stop mitosis by preventing polymerisation and depolymerisation of spindle fibres in anaphase

Question 18

Mechanism of action of platinum?

Answer 18

Forms platinated inter- and intra-strand adducts

Each adduct has a large side-group, stopping replication and inhibiting DNA synthesis and apoptosis

Question 19

Mechanism of action of topoisomerase-1 inhibitors?

Answer 19

Inhibit re-ligation of a DNA strand when it has been cleaved due to supercoiling
Therefore have single and double stranded breaks, causing apoptosis

Question 20

Mechanism of action of methotrexate as a chemo drug?

Answer 20

Inhibits dihydrofolate reductase, stopping production of purines

Question 21

Mechanism of action of 5-fluorouracil?

Answer 21

Stops the folate cycle, inhibiting production of pyrimidine bases

Question 22

Mechanism of action of vinca alkaloids and taxoids?

Answer 22

Vinca alkaloids - inhibit polymerisation of spindle fibres

Taxoids - inhibit depolymerisation of spindle fibres

Question 23

What is response to chemotherapy based on?

Answer 23

Performance score of an individual patient

Clinical stage

Prognostic factors/score

Side effects vs anticipated/best outcome

Question 24

How is the performance score calculated?

Answer 24

0 = full health
1 = jaded - can do activities but struggle at work
2 = cannot work, spends 50% of day resting
4 = bed-bound
5 = dead

Question 25

Routes of administration of chemotherapy drugs?

Answer 25

IV - bolus - infusional bag - continuous pump infusion ``` PO SC Into a body cavity Intralesional Intrathecally Topically IM ```

Question 26

Types of IV pumps for chemo?

Answer 26

PICC line - a peripherally inserted catheter. Patient can go home with it. Well tolerated. Hickman line

Question 27

What are the mechanisms of resistance to alkylating agents?

Answer 27

P-glycoproteins allow the drug to enter the cell, but can be modified to pump it straight back out again before causing damage Drug inactivated/neutralised by proteins in the cytoplasm eg glutathione. Bind to it and drug is no longer harmful so cannot get to genetic material in nucleus Enhanced repair mechanisms of DNA once damage has been done

Question 28

How can renal failure occur with chemo?

Answer 28

Often multi-factorial | Hyperuricaemia caused by rapid tumour lysis leads to precipitation of urate crystals in renal tubules

Question 29

What are the different patterns of emesis with chemo?

Answer 29

Acute phase: 4-12 hours Delayed onset: 2-5 days Chronic phase: persist for up to 14 days

Question 30

Which chemo causes minimal alopecia?

Answer 30

Platinum

Question 31

What skin toxicity is there in chemo?

Answer 31

Locally - irritation and thrombophlebitis of veins - local extravasation, goes into surrounding tissue instead of vein, leading to necrosis. Higher risk with poorer veins General - bleomycin can cause hyperkeratosis, hyper-pigmentation, ulcerated pressure sores - Beau's lines on nails

Question 32

How does mucositis present with chemo?

Answer 32

(GI epithelial damage) Sore mouth and throat with many ulcers - commonly worse in oropharynx Diarrhoea GI bleed

Question 33

What problems with the heart can chemo cause?

Answer 33

Cardiac myopathy (doxorubicin and cyclophosphamide) Arrhythmias (cyclophosphamide and etoposide)

Question 34

What lung toxicity can chemo cause?

Answer 34

Pulmonary fibrosis | -do not give oxygen, makes it worse

Question 35

Give a summary of ADRs of chemo

Answer 35

``` Acute renal failure GI perforation at site of tumour Disseminated intravascular coagulopathy Vomiting Alopecia Skin toxicity - thrombophlebitis, extravasation, hyper pigmentation Mucositis Cardio-toxicity - cardiac myopathy and arrhythmias Haematological - neutrophils and platelets Cystitis Myalgia Neuropathy Sterility ```

Question 36

How can absorption of chemo be affected?

Answer 36

Nausea and vomiting | Compliance

Question 37

How can abnormalities in distribution of chemo occur?

Answer 37

Can sit in ascitites Weight loss Reduced body fat

Question 38

How can abnormalities in elimination of chemo occur?

Answer 38

Liver and renal dysfunction | Other medications

Question 39

How can abnormalities in protein binding occur in chemo?

Answer 39

Low albumin | Other drugs

Question 40

Important DDIs of chemo?

Answer 40

Vincristine and itraconazole (anti fungal) - increased neuropathy Capecirabine (oral 5-FU) and warfarin Methotrexate and penicillin or NSAIDs Cepcitabine and St. John's Wort or grapefruit juice

Question 41

What factors affect the dose of chemo given?

Answer 41

The patient's BMI and/or surface area Drug handling ability of the patient eg liver function, renal function General well-being - performance status and co-morbidities

Question 42

How is the response of cancer to chemo monitored?

Answer 42

Radiological imaging Tumour marker blood tests Bone marrow cytogenics

Question 43

What other monitoring is done with chemo?

Answer 43

Drug levels eg methotrexate drug assays to ensure clearance from the blood Organ damage eg creatinine clearance of echocardiogram

Question 44

What is the ultimate measure of trial outcomes?

Answer 44

Overall survival