lecture 19 - principles of cancer therapy

Question 1

clinical presentation of cancer

Answer 1

primary tumour = local effects due to expansion (mass, bleeding, obstruction, hoarseness)

metastasis = distant effects
• lymph nodes (mass)
• lungs (breathlessness)
• brain (headache)

para-neoplastic syndromes, generalised effects due to:
• hormonal (hypercalcaemia)
• autoimmune (myasthenia gravis)
• undefined mechanisms (finger clubbing)

Question 2

diagnosis

Answer 2

• by tumour biopsy and histopathology
• identify tissue of origin, grade and prognostic markers
• staging (extent of tumour spread)
• functional assessment as to how patient is likely to cope with disease and treatment (eg. low lung function making resection of lung cancer less appropriate)

Question 3

cancer surgery

Answer 3

• most effective treatment for curing cancer (complete excision with margin of normal tissue)
• also used for diagnosis, staging (assessing lymph node spread), local control, palliation

Question 4

radiation therapy

Answer 4

• ionising radiation damaging DNA and generating ROS that damage cellular structures, inducing
cell death

• usually given as external beam radiotherapy

• planned according to treatment field (location), dose to tumour (and consequentially to normal
tissue), number of treatments

Question 5

chemotherapy

Answer 5

using chemical to kill disease causing cells in the body
e.g. bacteria, fungi, cancer, viruses

(in contrast, drug therapy uses chemical to modulate body processes e.g. mood, arterial BP)

Question 6

selective toxicity

Answer 6

when toxicity is produced in cancer cells without (or with less) effects in host cells

achieve by exploiting differences between host and cancer cells
• unique target in pathogen
• target is structurally or functionally different to host

Question 7

therapeutic index (TI)

Answer 7

• indicator of selective toxicity

* ratio of dose required to produce toxic effect, over dose required to produce desired effect

Question 8

tumour growth and treatment response

Answer 8

• growth by division of one malignant cell (clinically evident at 108 cells, lethal at 1012 cells)
• growth (exponential) shown by straight line in logarithmic scale
• chemotherapy dose kills constant proportion of tumour cells (repeated doses required, continued
after clinical disappearance

Question 9

combination therapy

Answer 9

more effective than single agents

criteria:
• some activity as single agent
• different mechanisms of action
• different side-effects

Question 10

adverse effects of chemotherapy

Answer 10

common

adverse effects determine dose and dosing interval of chemotherapy

most reversible or clinical manageable

most related to main action of drug:
• anti-proliferation (myelosuppression, mucositis, alopecia, sterility)
• mutagenesis (second cancers, teratogen)
• microtubule disturbance (peripheral neurotoxicity)
• sex steroid deficiency (decreased libido, impotence, flushing)

Question 11

indications for chemotherapy

Answer 11

• for cure (high cure rates in acute lymphoblastic leukaemia, testicular cancer, Hodgkin’s disease)
• with surgery (after surgery to eradicate microscopic tumours, eg in breast and colorectal cancers)
• with radiotherapy (combined modality treatment for head and neck, cervical cancer)
• palliation (improve symptoms, survival time)