Lecture 20: Principles of Cancer Therapy

Question 1

Clinical presentation of cancer?

Answer 1

Primary tumour -local effects due to expansion, breach of epithelial surfaces, narrowing of body tubules

Metastasis -Distant effects involving lymph nodes, lungs, brain, liver or bone.

Paraneoplastic syndromes -Generalised effects due to hormonal (eg. gynamcomastia due to beta-HGC), autoimmune or undefined mechanisms.

Question 2

Principles of Cancer diagnosis and investigation?

Answer 2

Diagnosis -pathological diagnosis, requiring a biopsy and histopathology to exclude benign pathology

Staging -Determines extent of involvement accoring to staging systems (eg. TNM system)

Functional assessment -of if the patient will actually respond/cope with the treatment.

Question 3

Key questions for cancer treatment?

Answer 3

1. Is surgucal rescection or curative treatment possible?
2. what treatment modalities are required for best outome
3. Are different treatment options available

Question 4

Surgery?

Answer 4

most effective cancer treatment with 40% cured by surgery

complete excision with margin of normal tissue

(or: for diagnosis via excision biopsy, staging, local control, bypass obstruction for palliation)

Question 5

Radiation therapy?

Answer 5

Ionising radiation mode of cell death

• energy from radiation damages DNA and generates free radicals from water.

Therapeutic radiotherapy

• External beam radiotherapy, planned according to treatment fields, dose to tumour and normal tissue.
• Is a component of curative treatment for head and neck cancer

Question 6

cancer chemotherapy

Answer 6

Using chemicals to kill disease causing cells in the body

Rather than drug therapy: using chemicals to modulate body processes

Question 7

Selective toxicity

Answer 7

The goal of chemotherapy

toxicity produced in the cancer cells without (or with very little) negative effect in host cells

1. unique target in the pathogen
2. target is structurally different in pathogen
3. target is functionally different in pathogen

Question 8

Therapeutic index

Answer 8

TI = EC₅₀ for unwanted toxicity/EC₅₀ for therapeutic activity

The larger the number the number the more favourable the situation

Question 9

Classification of cancer chemo drugs

Answer 9

1. alkylating agents - bind DNA (cyclophosphamide)
2. antimicrotubule
3. antimetabolites
4. hormonal agents
5. targeted therapies
6. topoisomerase-interactive drugs-inhibit DNA organisation
7. platinum-based drugs
8. vasular targeting therapies

Question 10

First order kinetics of tumour cell growth and chemotherapy

Answer 10

Tumour growth

• starts as one cell
• 10⁸ before it’s clinically relevant
• 10¹² before it’s lethal

Chemtherapy killing

• each dose kills a constant proportion of tumour cells
• repeated dose required
• continued after clinical dissappearance

Question 11

Combination Chemotherapy

Answer 11

more effective than single agent

• some activity as single agent
• differing mechanisms of action
• different side-effect profiles

Question 12

BEP?

Answer 12

Bleomycin - induces DNA breaks - lung toxicity

Etoposide - Topoisomerase II poison - bone marrow

Cisplatin - induces DNA crosslinks - peripheral nerves

Question 13

Adverse effects of cancer chemotherapy?

Answer 13

Antiproliferative - myelosuppression, alopecia, sterility

mutagenesis - second cancers, teratogenicity

Mircotubule disturbances- peripheral neurotoxicity

sex steroid deficiency - Decreased libido, impotence, flushing

Question 14

Indications for cancer chemotherapy?

Answer 14

CURE - high cure rates with acute lymphoblastic leukemia, testicular cancer

WITH RADIATION

• combined modality therapy for head and neck, cervical cancer

WITH SURGERY

• adjuvant chemo for node-positive breast and colorectal

PALLIATION

• improves symptoms and survival (eg. with Lung cancer)