Lecture 2 - Modes of treatment.

Question 1

What are the priorities in cancer?

Answer 1

Prevention
Early diagnosis
Total eradication

Question 2

What are the aims in cancer management?

Answer 2

1. Cure - eradication of tumour and metastasis
2. Remission/mitigation - significant reduction in tumour load
3. Symptomatic/palliation - treatment of secondary complications, relief of symptoms
4. Terminal care - improve quality of life, optimise symptom control.

Question 3

What is a chemosensitive tumour?

Answer 3

It means that the tumour is more sensitive to chemicals and it is easier to cure. Examples are leukemia and lymphoma.

Question 4

What is the purpose of palliation?

Answer 4

It is the relief of symptoms and prolongation of life where cure is not possible. It is possible to prolonged life by 2-18 months for solid tumours and 5-8 years for some leukaemias and lymphoma.
Example of drug used is antiemetics.

Question 5

List the modes of therapy available for cancer.

Answer 5

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

Question 6

What are the criteria for a surgery?

Answer 6

1. Well defined tumour
2. Non vital region
3. Non mutilating result
4. Resection/reconstruction of possible

Question 7

What are the criteria for radiotherapy?

Answer 7

1. Diffuse but localised tumour
2. Vital organ/ region (head, neck, CNS)
3. Adjuvant therapy
4. Palliation

Question 8

What are the criteria for chemotherapy?

Answer 8

1. Adjuvant therapy following surgery or radiotherapy
2. Neo-adjuvant prior to surgery or radiotherapy
3. Widely disseminated/ metastasised
4. Diffuse tumour (leukaemia)
5. Palliation
6. Some primary tumours

Question 9

How do chemotherapy works?

Answer 9

Chemotherapeutic agents exert their effect by killing cells that are rapidly dividing. This means these agents do not only kill tumour cells but also normal cells such as hair follicle cells and gastrointestinal mucosa.

Question 10

How do radiotherapy works?

Answer 10

It is the application of ionising radiation to treat disease.. Electromagnetic radiation and elementary particles deposit energy in materials through the processes of excitation and ionisation events. In radiotherapy therapy, a measured dose of irradiation is delivered to a defined tumour volume with care taken to inflict minimal damage to surrounding healthy tissue. Ionising radiation cause cellular damage by the formation of free radicals. To improve radiation therapy, the total dose of radiotherapy is given is small daily amounts. Most radiosensitive cancer like leukaemia, small cell lung cancer and myeloma are most affected.

Question 11

What are the palliative benefits of radiotherapy?

Answer 11

1. Pain relief
2. Reduction of headache and vomiting
3. Relief of obstruction
4. Preservation of skeletal integrity
5. Reversal of neurological impairment.

Question 12

List a few side effects of radiotherapy.

Answer 12

• anorexia, nausea, malaise
• mucositis eg diarrhea
• Alopecia
• Myelosuppression

Question 13

What is rationale for chemotherapy?

Answer 13

It is used to reduce the volume of disease and palliative symptoms caused by cancer. It is most commonly used in advanced cancers and after the primary tumour has been controlled by surgery or radiotherapy. This is to eradicate the micrometastatic disease and reduce the risk of recurrence.
Before choosing cytotoxic chemotherapy, the features of the tumour growth must be recognised; these include the cell cycle time, growth fraction and number of cells.
The tumour have to be over 109 cells as the chemotherapy proves to be less effective before that.
Chemotherapeutic agents are used as a combination and the treatment is given with intermittent basis with shortest delays between treatment as to allow recovery of most sensitive normal tissue (bone marrow and gut)

The possible combination of drugs used often have synergistic killing effect. Another combination is to use drugs that acts on different stages of cell cycle.

Question 14

Define adjuvant therapy.

Answer 14

It is define as treatment given in absence of macroscopic evidence of metastases to patient at risk of recurrence of micrometastases. Micrometastatic spread by lymphatic and haematological dissemination often occurs early in the development of a primary tumour

Question 15

List the drug target for cancer.

Answer 15

1. Anti metabolites (Stop cell from making building block of DNA)
2. Agent binding to DNA (stop DNA synthesis)
3. Microtubule inhibitors (stop cell from making components needed to separate)

Question 16

List some common drugs used and their mechanism of action.

Answer 16

Methotrexate ( an anti metabolite which inhibits purine synthesis and DTMP synthesis)
5-Fluorouracil (an antimetabolite which inhibit DTMP synthesis)
Azathioprine (an anti metabolite)
Cisplatin ( Agent binding to DNA )

Question 17

List the side effects of chemotherapy.

Answer 17

• Myelosuppression (reduced platelets and white blood cells
• Gastrointestinal tract and bladder (erosion and ulceration)
• Skin and hair (hair loss)
• Fertility (spermatogenesis is inhibited)
• Teratogenic effects (methotrexate)
• Genetic damage (DNA of spermatozoa or ova is -changed)
• Carcinogenesis
• Nausea and vomiting

Question 18

Give examples how to minimise the side effects.

Answer 18

1. For myelosuppression, transfusions of platelets, marrow and blood. Growth factors(filgrastim) are used. Time of doses, careful monitoring and isolation.
2. Nausea and vomiting, antiemetics are used. Dopamine antagonists (prochlorperazine) 5-HT3 antagonist(Ondansetron) Benzodiazepine(Lorazepam) Corticosteroids(Dexamethasone) Cannabinoids (Nabilone)
3. Mucositis, use mouthwashes
4. Subfertility, spermbank, IVF
5. Cardiomyopathy, ECG monitoring and cardiac glycosides
6. Hepatotoxicity, Liver function test
7. Anti-folate overdose, use of folinic acid
8. Nephrotoxicity, Overhydration and diuresis specially of ifosfamide.
9. Alopecia, use of wigs.

Question 19

Give the different definition of responses.

Answer 19

Complete response - complete disappearance of all detectable disease
Partial response - More than 50% reduction
Stable disease - No change or less than 50% reduction or less than 25% increase
Progressive disease - More than 25% increase in size of tumour.