Principles of Cancer Treatment (Part 1) Flashcards
Describe tumour growth kinetics
- logarithmic: once detected, grows quickly
- tumour growth is in equilibrium: slope of the curve depends on ratio of cell division to cell loss, doubling time, growth fraction
- past 30 generations, clinical symptoms show and there is exponential cell growth
What is doubling time, and is doubling time consistent throughout all types of cancers?
- Doubling time refers to the time taken for the tumour to double its mass.
- Solid tumours have longer TD than hematological malignancies.
- Large variations in TD exist even amongst the same kind of tumour in different patients.
When does a tumour metastasise and how does it metastasise?
- Before clinically detectable, and when it is clinically detectable
- through the blood and lymphatic system
- proteases release lytic enzymes that dissolve the basement membrane.
- cells invade and move through the defect due to increased cell motility and decreased cell-to-cell adhesiveness.
- altered cell membrane receptors facilitate the binding of the tumour to the basement membrane.
What are the goals of cancer treatment?
- curative
- prolong quality and duration of life
- symptom relief (palliative treatment)
- clinical trials and experimental therapies
What are the characteristics of ideal cancer treatment?
- safe, effective and discriminating
- actions should be limited to cancer cells
- should have few side-effects
- should return patient to former state of health
Surgery characteristics
- oldest cancer treatment
- curative for localised disease
- commonly used to remove primary cancer or metastatic masses
What is surgical debulking?
- pain or symptom relief
- reduce size of tumour to increase efficacy of other therapies (radiotherapy, chemotherapy etc.)
Radiation therapy
- destruction of cancer cells by ionising radiation
- generates free radicals to kill cancer cells in rapid division by targeting their cellular DNA.
- radiocurability depends on the size and location of tumour, type of tumour and tumour radiosensitivity.
How is radiation therapy delivered and expressed (units-wise)?
by external beam and brachytherapy
expressed in Gray (Gy)
- typical dose for glioma: 60Gy
- typical dose for breast cancer: 50Gy
What is the dose-limiting factor for radiation therapy?
Normal tissue damage
- early effects to rapidly dividing tissues
- late effects in organs
Serious radiation toxicities:
- bone marrow
- liver
- stomach
- intestine
- rectum
- brain, CNS
- lung
- fetus
- anemia
- hepatitis
- ulcer / hemorrhage
- ulcer / perforation
- ulcer / stricture
- infarct / necrosis
- pneumonitis / fibrosis
- death
How is palliation of pain achieved through radiotherapy?
- external beam
- strontium-89
Chemotherapy
- most useful for treatment of systemic or disseminated disease (including micrometastases)
- used as adjunct to surgical/radiotherapy and palliation
Basic principles of chemotherapy
- Drug kills a constant proportion of tumour cells rather than a constant number of cells (first order kinetics).
- It has the greatest effect on cells that are actively dividing.
- Drugs have a narrow therapeutic index, treatment is. a balance between efficacy and toxicity
- Combination therapy can be used to increase treatment outcome.
Drug kills a constant proportion of cells rather than a constant number of cells.
- first order tumour kinetics
- number of cells before therapy determines the number of cells surviving therapy.
- early treatment when tumours are small gives better results.
Drugs have narrow therapeutic index, hence treatment is a balance between efficacy and toxicity.
- Tolerance
Cure - high
Extend life - moderate
Palliate symptoms - low - Special concerns
Cure - delayed and late side effects
Extend life - value of added time
Palliate symptoms - symptoms control - Challenges in patient selection and management
Cure - don’t treat patients who have already been cured
Extend life - treat when added time outweighs side effect
Palliate symptoms - treat when not treating results in reduced QoL
What are the advantages and disadvantages of combination therapy?
Advantages:
- maximum cell kill within acceptable toxicity
- broad coverage against multiple cell lines
- slower emergence of resistant strains
Disadvantages:
- multiple toxicities with greater patient discomfort
- impact of dose effect
- complicated to administer
- more expensive
Application of basic principles of chemotherapy
- Drug kills a constant proportion of tumour cells rather than a constant number
- It has the greatest effect on cells that are actively dividing
- Drugs have a narrow therapeutic index, thus treatment is a balance between efficacy and toxicity.
- Combination chemotherapy can be used to improve treatment outcome
- Repeat treatment cycles
- Treat ASAP, when the disease is in the early stage
- Know intent of treatment, monitor for side effects
- Where possible
What is the protocols concept?
- different tumours respond to different cocktails of chemotherapy
- efficacy is established through clinical trials
- different centres have different protocols of treatment
What is the AC protocol for breast cancer?
- IV Doxorubicin 60mg/m2, day 1
- IV Cyclophosphamide 600mg/m2, day 1
- Repeated every 21 days
What is the FOLFIRI colon protocol (weekly)?
- IV 5-fluorouracil, 500mg/m2
- IV folinic acid, 20 mg/m2
- IV irinotecan, 125 mg/m2
to be administered once every weekly (D1, 8, 15, 22), for 42 days
What are the paclitaxel and carbo+gemzar lung protocols?
- Paclitaxel:
» IV Paclitaxel 80mg/m2 (D1, 8, 15, 22) for 28 days - Carbo + Gemzar (weekly):
» IV Carboplatin 100mg/m2 (D1, 8, 15) for 28 days
» IV Gemcitabine 1000mg/m2 (D1, 8, 15) for 28 days
How are doses administered?
based on BSA
BSA (m2) = square root of (weight x height) / 3600
How to intensify the doses?
- increase the number of doses
- reduce the interval
Selection of chemotherapy treatment algorithm:
- Determine histological diagnosis, tumour staging and other prognostic variables
- Identification of treatment option and benefit
- Assessment of comorbid conditions and psycho-social environment
- Determine treatment-related risks
- Assessment of risk versus benefit
- Selection of therapeutic regimen