Principles of Treatment Flashcards
Smallest clinically detected mass of a tumour
1g (10^9 cells)
Tumour is usually detected at ____?
10g (10^10 cells)
Lethal size of a tumour?
1kg (10^12 cells)
Factors affecting the slope of the Gomperzian Growth curve
Ratio of cell division to cell loss
Growth fraction
Doubling time (TD)
Host factors
What are the host factors that affect the slope of the Gomperzian Growth Curve?
Vasculature
Space restrictions
Necrosis
Presence of other cell populations
Mechanism of Metastasis?
Dissolution of basement membrane by lytic enzymes, facilitating invasion and movement
Invasion and movement through defects due to increased cell motility, decreased cell to cell adhesiveness
Binding of tumour to basement membrane through the mediation of altered receptors on the cell surface
What are the goals of cancer treatment??
Curative
Maintenance of quality and duration of life
Symptom relief
Clinical trials for experimental therapies
What are the characteristics of an ideal treatment?
Safe, effective and discriminating
Targets only the cancer cells
Few side-effects
Return patient to former state of health
Uses for surgical debulking?
Decrease the size of the tumour to allow chemo/radiotherapy to be more effective
Pain/symptom relief
Remove source of ectopically expressed hormones
Prevention - removal of polyps, moles
MOA of radiation therapy?
Destruction of cancer cells by ionizing radiation
Target of radiation therapy?
Cellular DNA
Two methods of radiation therapy?
1) External Beam
2) Brachytherapy/ Interstitial brachytherapy - Insertion of implant near or inside tumour
Curability of radiation therapy depends on?
Size, location of tumour, type of tumour, tumour radiosensitivity
Dose-limiting factor of radiotherapy?
Normal tissue damage
Preventive measure to minimise normal tissue damage?
RT with curative intent fractionated and given in small doses
What are the basic principles of cancer chemo?
1) Drug kills a constant proportion of tumour cells
2) Chemo has the greatest effect on actively proliferating cells
3) Chemo drugs has a narrow therapeutic index, treatment is a balance between toxic effects an efficacy
4) Combi therapy can be used to improve treatment outcomes
Advantages of Combi therapy
1) Maximum cell kill
2) Broad coverage against multiple cell lines
3) Slower emergence of resistant strains
Disadvantages of combi therapy
1) Complicated and expensive to administer
2) Impact of dose effect
3) Multiple toxicities with greater patient discomfort
What is the unit for chemo doses?
1) Unit weight
2) Body surface area
What is the benefit of BSA
Provides a more accurate cross-species comparison of activity and toxicity
Formula of BSA?
Square root (Weight [kg]) * Height [cm] / 3600)
Function of the schedule of administration?
1) Followed to achieve optimal therapeutic benefit with minimal toxicity
2) Allow for “drug rest”
How do you intensify the chemo treatment?
1) Reduce dosing interval
2) Increase dose
Factors affecting the selection of chemotherapy regimen?
1) Histological documentation of tumour type
2) Stage of disease
3) Prognostic variable
4) Patient-related variables
5) Toxicities
6) Risk vs benefits
What are the patient-related variables affecting selection of chemo?
1) Organ function
2) Concomitant disease
3) Nutritional status
4) Social
5) Economic
6) Cultural
7) Lifestyle
What are the factors affecting response to chemotherapy?
1) Drug
2) Tumour
3) Patient
What are the drug factors affecting response to chemo?
1) Drug intensity
2) Drug scheduling
3) Cell-cycle specificity
What are the tumour factors affecting response to chemo?
1) Size
2) Location (Anatomic site)
3) Resistance
4) Blood supply
What are the patient factor affection response to chemo?
1) Drug tolerance
2) Renal/ Hepatic function
Combination therapy is used to overcome what challenges?
1) Sensitivity - Tumour may be non responsive to clinically achievable dose
2) Toxicity - Avoid the use of high doses
3) Resistance - Inherent genetic instability can result in non-random mutation that confers resistance
What are the mechanism of chemo resistance?
1) Decrease accumulation of drug - Via increased efflux, decrease uptake and altered intracellular trafficking
2) Decrease in drug activation
3) Increase in drug metabolism
4) Increase ability to repair drug-induced damage
5) Use alternative biochemical pathway
6) Altering drug target
Desirable characteristics of combi therapy?
1) Must not antagonise one another
2) Effective
3) Different dose-limiting toxicities
4) Different pharmacological action
5) Increase overall intensity of treatment
6) Given in a dose equivalent to that used when the drug is given alone
The larger the tumour, the _______?
1) Greater chance of metastasis
2) Greater probability of drug-resistance cells
3) Greater chance of poor drug distribution - Central necrosis
Where are the sanctuary sites? Why do they affect chemo outcome?
CNS , Testis
1) Poor drug penetration
2) Poor blood supply
