Modes of treatment

Question 1

What are the priorities when dealing with cancer?

Answer 1

Prevention,
Early Detection,
Total Eradication

Question 2

What is the hierarchy of aims in cancer management?

Answer 2

Cure - eradication of tumour and metastasis.
Remission/mitigation - significant reduction in tumour load. Increased survival.
Symptomatic / palliation - treatment of secondary complications. Relief of symptoms.
Terminal care - improve quality of life. Optimize symptom control.

Question 3

why is there no sufficient cure for most solid tumours? What happens

Answer 3

For most solid tumours local control is possible but not sufficient for cure because of the presence of systemic (microscopic) disease, while haematological cancers are usually disseminated from the outset.

Question 4

Which cancers are super sensitive to chemo that bulky metastases can be cured and which ones are not?

Answer 4

leukaemia and lymphoma = chemosensitive

Breast and colorectal = no current cure

Question 5

What is Palliation and when does it occur?

Answer 5

When cure is no longer possible, palliation, i.e. relief of tumour symptoms and prolongation of life

Question 6

What are the modes of therapy? (4)

Answer 6

1. Surgery - excision of primary tumour.
2. Bone marrow transplantation - for some leukaemias.
3. Radiotherapy
4. Drugs - cytotoxic chemotherapy, hormone therapy, immunotherapy.

Question 7

What are the factors that govern which treatment is used?

Answer 7

1. empirical clinical evidence;

2. practical considerations

Question 8

When is surgery used?

Answer 8

Well-defined solid tumour
Non-vital region (e.g. mastectomy)
Non-mutilating result
Resection/reconstruction possible (e.g. gut)

Question 9

When is radiotherapy used?

Answer 9

Diffuse but localized tumour (e.g. lymphoma)
Vital organ / region (e.g. head and neck, CNS)
Adjuvant therapy (e.g. post mastectomy)
Palliation

Question 10

When is chemotherapy used?

Answer 10

Adjuvant therapy following surgery or radiotherapy
Neo-adjuvant therapy prior to surgery or radiotherapy
Widely disseminated / metastasized
Diffuse tumour (e.g. leukaemia)
Palliation
Some primary tumours (e.g. Hodgkin’s lymphoma)

Question 11

Why does chemotherapy cause the hair to fall out?

Answer 11

Kill cells that rapidly divide. NOT tumour specific so also kill normal rapidly dividing cells such as hair follicle cells and gastrointestinal mucosa

Question 12

How does Radiotherapy work? Give examples

Answer 12

application of ionizing radiation to treat disease - electromagnetic radiation and elementary particles deposit energy in materials through the processes of excitation and ionization events. Common forms of ionizing radiation include photon beams (X-rays and gamma rays) and electrons (b-particles).

Cell death = approx 40 double strand breaks in DNA

Question 13

What are the palliative benefits of radiotherapy? (5)

Answer 13

1. Pain relief e.g. bone metastases.
2. Reduction of headache and vomiting of raised intracranial pressure from CNS metastases.
3. Relief of obstruction of bronchus, oesophagus, ureter and lymphatics.
4. Preservation of skeletal integrity from metastases in weight-bearing bones.
5. Reversal of neurological impairment from spinal cord or optic nerve compression by metastases.

Question 14

What are the acute side effects of radiotherapy?

Answer 14

anorexia, nausea, malaise
Mucositis, e.g. oesophagitis, diarrhoea
Alopecia
Myelosuppression

Question 15

What are the later side effect of radiotherapy?

Answer 15

Skin : Ischaemia, ulceration
Bone : Necrosis, fracture
Mouth : Xerostomia, sialitis, ulceration
Bowel : Stenosis, fistula, diarrhoea
Bladder : Cystitis
Vagina : Dyspareunia, stenosis
Lung : Fibrosis
Heart : Pericardial fibrosis, cardiomyopathy
CNS : Myelopathy
Gonads : Infertility, menopause

Question 16

Describe the rationale for the use of chemotherapy?

Answer 16

For the majority of the solid tumours chemotherapy is used to reduce the volume of disease and palliative symptoms caused by cancer.

A further indication for chemotherapy is to use it as an adjuvant after the primary tumour has been controlled by either surgery or radiotherapy - this is to eradicate subclinical micrometastatic disease and reduce the risk of recurrence.

Neoadjuvant chemotherapy is also used increasingly to debulk or downstage primary tumours prior to the definitive treatment, eg surgery or radiotherapy.

Chemotherapy is usually used systemically either intravenously or orally.

Question 17

Define adjuvant therapy in relation to cancer

Answer 17

treatment given in the absence of macroscopic evidence of metastases, to patients at risk of recurrence from micrometastases

Question 18

What is the time frame that chemotherapy should be given?

Answer 18

The treatment should be delivered on an intermittent basis with the shortest possible time between treatments that allows recovery of the most sensitive normal tissue (e.g. bone marrow or gut).

Question 19

How can chemotherapy be given?

Answer 19

Wherever possible it is preferable to use drugs with known synergistic killing effects, for example the combination of oxaliplatin and 5-fluorouracil.

Another possibility is to use a combination of drugs that can kill cancer cells at different stages of the cell cycle.

Some regimens use alternating cycles of different drug combinations - giving the less effective drug first.

Question 20

How do Microtubule inhibitors work? What stage of the cell cycle do they target? Give examples

Answer 20

Stop cells making components needed to separate

Target those in G2 phase

E.g. Vinca alkaloids, Docetaxol, Paclitaxel

Question 21

How do Agents binding to DNA work? What stage of the cell cycle do they target? Give examples

Answer 21

Stop DNA synthesis

Target the S phase

e.g. Alkylating agents, anti-tumour antibiotics, platinum compounds

Question 22

How do Anti-metabolites work? What stage of the cell cycle do they target? Give examples

Answer 22

Stop cells making the building blocks of DNA

Target G1 phase

e.g. methotrexate, azathioprine

Question 23

What are the side effects of chemotherapy cytotoxic action?

Answer 23

Myelosuppression - rapid fall in blood count with a nadir for WBC and platelets at 7 days.= frequent infections, impairs coagulation leading to bruising + bleeding

GI tract + bladder - erosion and ulceration in mucous membranes = mouth ulcers and diarrhoea

Skin + Hair - hair loss common, reversible

Fertility - Spermatogenesis is inhibited and sometimes there may be permanent male infertility, e.g. from alkylating agents. Female infertility is less common

Teratogenic action - cytotoxics are particularly hazardous during the first trimester of pregnancy, I.e. during organogenesis and the risk is greatest for methotrexate and the alkylating agents

Question 24

What are the side effects of chemotherapy -mutagenesis?

Answer 24

Genetic damage - heritable defects may be caused if the DNA of spermatazoa or ova is damaged, although most mutations are lethal for the cell. These risks are yet to be fully assessed but are avoided by contraception during treatment.

Carcinogenesis - cytotoxic drugs are able to both cause and cure cancer. The same is true for radiotherapy. Hence more selective methods for treating cancer are required

Question 25

Nausea and vomiting side effects can occur with chemotherapy. Why does this occur and what can be given to help?

Answer 25

symptoms result from direct stimulation of the chemoreceptor trigger zone. Anti-emetics are therefore used alongside traditional chemotherapy regimens

Question 26

What can be done to minimise side effects?

Answer 26

The aims are to either reduce discomfort, morbidity and mortality or to increase the tolerable dose threshold and thus the dose that can be used.

Close monitoring is extremely important particularly full blood counts.

Prevention is used wherever possible

Forced diuresis is now routinely given with nephrotoxic and bladder-toxic drugs to reduce contact time and urine concentration. This involves modest over-hydration before therapy followed by a diuretic to maintain a high urine output for at least 24h following therapy (e.g. mannitol).

Question 27

What are the methods of minimization of Myelosuppression?

Give examples

Answer 27

Transfusions e.g. blood platelets

Growth factors e.g. Filgrastim

Timing of doses, careful monitoring, isolation in sterile environment

Question 28

What are the methods of minimization of Nausea and vomiting?
Give examples

Answer 28

Anti-emetics:
dopamine antagonists e.g. Prochlorperazine

5HT3 antagonists e.g Ondansetron

benzodiazepines e.g metoclopramide, Lorazepam

corticosteroids e.g Dexamethasone

cannabinoids e.g Nabilone

Question 29

How would you minimise the following side effects of chemotherapy? Give examples where applicable

Mucositis; mouth ulcers
Subfertility
Cardiomyopathy
Hepatotoxicity
Anti-folate overdose
Nephrotoxicity / Haemorrhagic cystitis
Alopecia

Answer 29

Mucositis; mouth ulcers - Oral hygiene e.g. mouth wash

Subfertility - sperm banking, IVF

Cardiomyopathy- ECG monitoring, cardiac glycosides

Hepatotoxicity - LFTs (pre and post)

Anti-folate overdose - for methotrexate - Folinic acid

Nephrotoxicity / Haemorrhagic cystitis - Hydration and forced diuresis (for ifosfamide and cyclophosphamide) e.g. Mesna

Alopecia - Scalp tourniquet or chilling, wigs

Question 30

What are the categories of “response to treatment”?

Answer 30

Complete response: complete disappearance of all detectable disease.

Partial response: More than 50% reduction in the product of the bidimensional diameters of the tumour

Stable disease: No change, or <50% reduction and <25% increase

Progressive disease: Increase in size of tumour by at least 25% at any site