Chemotherapy

Question 1

Give the molecular target and two indications for Imatinib

Answer 1

Targets the fusion protein Bcr-Abl. It is used to treat chronic myeloid leukaemia and gastrointestinal stromal tumour. It inhibits the Bcr-Abl tyrosine kinase.

Question 2

What tumour diameter is widely considered to be the diagnostic threshold?

Answer 2

1cm.

Question 3

Describe the ‘fractional cell kill hypothesis’

Answer 3

This tells us that a defined chemotherapy dose (a concentration over a period of time) will kill a fixed fraction of cancer cells. This explains why repeated dose cycles are needed.

Question 4

When deciding how frequently a patient needs chemotherapy cycles the recovery of what parameter do we need to consider?

Answer 4

Blood count (bone marrow) recovery. This will likely recover more quickly and more completely than cancer cell numbers. Keeping hitting suppressed bone marrow with chemotherapy just has the effect of increasing the risk of neutropenic sepsis even higher.

Question 5

Name some cancers highly sensitive to chemotherapy.

Answer 5

Lymphomas, germ cell tumours, Wilm’s tumour, neuroblastoma, small cell lung tumours.

Question 6

Name some cancers modestly sensitive to chemotherapy.

Answer 6

Breast, colorectal, bladder, ovary, cervix, non small cell lung tumour.

Question 7

Name some cancers with low sensitivity to chemotherapy.

Answer 7

Prostate, renal cell, brain tumours and endometrial cancers.

Question 8

How do alkylating agents work?

Answer 8

They create cross links both within and between DNA strands, preventing replication as replication enzymes get ‘stuck’ . The replication fork cannot proceed effectively.

Question 9

What is a good example of an alkylating agent?

Answer 9

Platinum based drugs. Examples include Cisplatin and Oxaliplatin. These form both intrastrand and interstrand adducts. As well as impairing replication they impair repair also.

Question 10

How does 5-FU (5-Fluorouracil) work?

Answer 10

It forms an active metabolite which inhibits the enzyme THIMIDYLATE SYNTHASE which plays a role in the folate cycle and forms thymidine monophosphate which goes on to be incorporated into DNA as a thymine base.

Question 11

How does methotrexate exert its cytotoxic effect?

Answer 11

It inhibits the enzyme ‘dihydrofolate reductase’ which reduces dihydrofolate to tetrahydrofolate. This breaks the folate cycle and thus prevents the synthesis of thymine.

Question 12

What class of chemotherapy drugs do 5FU and Methotrexate belong to?

Answer 12

Anti-metabolites.

Question 13

How does Vincristine work?

Answer 13

Like all of the vinca alkaloids it inhibits the polymerisation of alpha and beta tubulin subunits into a microtubule needed for anaphase.

Question 14

How does Paclitaxel work?

Answer 14

It prevents depolymerisation that would take place in telophase so the cell gets ‘stuck’ in that part of the cell cycle.

Question 15

How can cells become resistant to an alkylating agent?

Answer 15

• Entry of agent decreases or exit increases.
• The agent is deactivated within the cell - typically by conjugation with glutathione.
• Lesions are repaired more effectively.

Question 16

If a patient is given an ambulatory chemotherapy pump an central venous line is needed, give and describe the two most commonly used types.

Answer 16

PICC Lines - placed via a peripheral vein into the arms into a central vein.
Hickman line - placed into the subclavian vein and tunnelled under the skin of the chest to prevent infection or accidental removal.

Question 17

What is tumour lysis syndrome and where may it occur?

Answer 17

Common in cancers with high turnover rates (such as leukaemias and lymphomas that are very chemosensitive. When we administer chemotherapy drugs cells lyse and release intracellular toxins into the blood stream. Urate can cause an intra-renal AKI. Potassium, phosphate and calcium are also released.

Question 18

What is a side effect of treating a GI lymphoma?

Answer 18

Once we start chemotherapy there is a risk that the tumour being rapidly killed can cause perforation of the wall of the GI system at this point.

Question 19

What haematological complication often occurs in acute myeloid leukaemia treatment?

Answer 19

DIC (Disseminated Intravascular Coagulation/Coagulopathy).

Question 20

Name some chemotherapy agents with high incidence rates of emesis?

Answer 20

• Cyclophosphamide (high dose).
• Ifosfamide (high dose)
• Cisplatin.

All are alkylating agents.

Doxorubicin (topoisomerase 2 inhibitor) and methotrexate are also emetogenic.

Question 21

Describe patterns of hair thinning during chemotherapy.

Answer 21

Hair thins at about 2-3 weeks after starting treatment, this is more pronounced with doxorubicin, cyclophosphamide and the vinca alkaloids than it is with the platinums. Hair may begin to regrow during therapy and this is not an indication that the treatment is not working.

Question 22

How can we attempt to manage hair loss in chemotherapy.

Answer 22

Scalp cooling is an option. Its level of success is variable.

Question 23

Why is central venous administration preferred to peripheral cannulas for some chemotherapy agents?

Answer 23

Some of these drugs cause profound thrombophlebitis and extravasation could lead to local tissue necrosis.

Question 24

What are ‘Bow’s Lines’ ?

Answer 24

These are lines on the nail that correspond with the stopping and resumption of nail growth to correlate with the number of chemotherapy cycles given.

Question 25

How might mucositis present?

Answer 25

• Sore mouth/throat.
• Diarrhoea
• GI Bleeding

Question 26

Which chemotherapy agents can cause heart problems?

Answer 26

Doxorubicin at doses above 500 mg / m2 can cause cardiomyopathy as can trastuzamab and high dose cyclophosphamide. Cyclophosphamide and etoposide can cause arrhythmias.

Question 27

Name a drug that causes pulmonary fibrosis? What medical treatment should we avoid that may make this worse?

Answer 27

Bleomycin. Avoid necessary oxygen therapy.

Question 28

What is the effect of co-administering Vincristine and itraconazole?

Answer 28

Worsens vincristine associated neuropathy.

Question 29

What is the effect of mixing Capecitabine and Warfarin?

Answer 29

The effect of warfarin can increase, driving up the INR.

Question 30

What is the possible interaction between Methotrexate and NSAID’s/Penicillins?

Answer 30

These drugs are all protein bound. Administration of these together may displace Methotrexate and increase its side effects, especially hepatotoxicity and myelosuppression.