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PR3136 > Principles of Cancer Treatment > Flashcards

Principles of Cancer Treatment Flashcards

1
Q

Cancer growth kinetics

A
  • logarithmic
  • once detectable, tumour tends to grow quickly
  • Gompertzian curve
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2
Q

Gompertzian curve

A
  • 3 phases (lag, log & stationary)

- >30 generations then clinically detectable (10^10)

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3
Q

Tumour growth equilibrium

A
  • slope of the curve depends on 3 factors
    1. Ratio of cell division to cell loss
    2. Growth fraction
    3. Doubling time (TD)
  • which in turn depends on host factors
    eg vasculature, presence of cell populations, space restrictions & necrosis
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4
Q

Doubling time (TD)

A
  • time taken for the tumour to double its mass
  • solid have longer TD than hematological malignancies
    (2-3 months vs 24h)
  • large variations in TD
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5
Q

Metastasis

A
  • can begin early before the tumour is clinically detectable
  • through 2 pathways
    1. Blood
    2. Lymphatic system
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6
Q

MOA of metastasis

A
  1. Tumour cells release lytic enzymes
    eg proteases
  2. Dissolution of the basement membrane by lytic enzymes
  3. Invasion & movement of the tumour cells through the defect due to increased cell motility & decreased cell-cell adhesion
  4. Binding of tumour to the basement membrane at another site through the mediation of altered receptors on the cell surface
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7
Q

Metastatic sites

A 
- metastatic patterns depends on the tumour type 
eg colon cancer to liver cancer (close proximity)
- can be anywhere 
- common :
  ~ liver
  ~ lungs 
  ~ lymph nodes
  ~ brain
  ~ skin
  ~ bone
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8
Q

Goals of cancer therapy (4)

A
  1. Curative
  2. Maintenance of quality & duration of life
  3. Symptom relief (palliative treatment)
  4. Clinical trials for experimental therapies
    - not the main goal, only when all options fail
  • goals must be negotiated with patient, family, physicians & healthcare team
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9
Q

Characteristics of an ideal treatment (3)

A
  • must be safe, effective & discriminating
    Safe : few side effects
    Effective : return the patient to former state of health
    Discriminating : limited to cancer cells only
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10
Q

Treatment modalities of cancer (3)

A
  1. Surgery
  2. Radiation
  3. Chemotherapy
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11
Q

Surgery (4)

A
  • oldest cancer treatment
  • curative for localised or primary cancer
  • reduce the size of tumour to increase efficacy of radiotherapy, chemotherapy & other therapies
  • play a major role in diagnosis, staging, relief of symptoms, reconstruction & prevention
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12
Q

Radiation (4)

A
  • destruction of cancer cells by ionising radiation
  • MOA is through generation of free radicals
  • may selectively destroy rapidly dividing cancer cells > normal cells
  • radiocurability depends on :
    1. size
    2. location of tumour
    3. type of tumour
    4. tumour radiosensitivity
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13
Q

Dose limiting factor of radiation therapy

+2 strategies to overcome

A

Normal tissue damage

  • early effects on rapidly dividing normal cells
  • late effects on organs
  • newer technologies to minimise normal tissue damange
  • fractionate radiotherapy
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14
Q

Toxicities of radiation therapy

A
  • fetal death
  • GI ulcer & hemorrhage
  • hepatitis
  • bone marrow effects
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15
Q

Uses of radiotherapy in cancer (4)

A
  • bone marrow transplant (total body irradiation)
  • supplement surgery
  • palliation of pain
  • relief of obstruction/compression
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16
Q

Chemotherapy (3)

A
  • drug therapy for cancer
  • most useful for systemic or disseminated disease (including micrometastases)
  • adjunct to surgery, radiotherapy & palliation
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17
Q

Principles of chemotherapy (4)

  • cell kill
  • greatest effect
  • therapeutic window
  • monotherapy?
A
  • kills a constant proportion of tumour cells
    (( repeat treatment cycles ))
  • greatest effect on actively dividing cells
    (( treat asap when disease in early stage ))
  • narrow therapeutic window
    (( know intent to treat & monitor side effects))
    Hence, treatment is a balance of efficacy & toxicity
  • combination chemotherapy may be used to improve treatment outcome
    (( where possible ))
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18
Q

Balance between efficacy & toxicity tolerance depends on __

A

Treatment goal (3)

  • curative
  • maintenance of quality & duration of life (extend life)
  • palliate symptoms
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19
Q

Efficacy & toxicity tolerance (curative) (3)

A
  • high tolerance for side effects
  • concerns over delayed & late side effects
  • avoid treating those who are already cured (over treatment)
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20
Q

Efficacy & toxicity tolerance (extend life) (3)

A
  • moderate tolerance for side effects
  • concern over value of added time
  • treat when added time outweighs side effects
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21
Q

Efficacy & toxicity tolerance (palliative care) (3)

A
  • low tolerance for side effects
  • symptoms control
  • treat only when not treating leads to lower QOL
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22
Q

Advantages of combination chemotherapy (3)

A
  • maximum cell kill within acceptable toxicity
  • broad coverage against multiple cell lines (use diff MOA)
  • slower emergence of resistant strains
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23
Q

Disadvantages of combination chemotherapy (4)

A
  • multiple toxicities with greater patient discomfort
  • impact of dose effect (additive dose effect)
  • complicated to administer
  • more expensive
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24
Q

Protocols

A
  • guidance on the different “cocktails” of chemotherapy to use
25
Q

Reasons for protocols (4)

A
  • different tumours responds to different “cocktails” of chemotherapy
  • efficacy established during clinical trials
  • numerous combinations hence it is impt to know the rationale behind the combinations
  • diff institutions have different protocols for treatment
26
Q

Calculation for dose of chemotherapy is based on __

A

Body Surface Area (BSA)

27
Q

BSA formula

A

square root [(height + weight)/3600]

height in cm
BSA in m^2

28
Q

Why is BSA used to calculate dose?

A
  • provides a more accurate cross-species comparison of activity & toxicity for many drugs
  • more closely related to cardiac output which determines blood flow to liver and kidney, subsequently determines drug elimination
29
Q

Importance of “drug rest” (2)

A
  • to allow for normal cells to recover

- achieve optimal therapeutic benefit with minimal toxicity

30
Q

How to intensify dose? (2)

A
  1. Reduce dosing interval

2. Increase the dose

31
Q

Selection of chemotherapy regimen steps (6)

A
  1. Determine histological diagnosis, tumour staging & prognostic variables
  2. Identification of treatment options & determine benefits
  3. Assessment of comorbid conditions & psychosocial environment
  4. Determine treatment related risks
  5. Assessment of risk vs benefits
  6. Selection of therapeutic regimen
32
Q

Factors affecting response to chemotherapy (3)

A
  1. Drug
    eg dose intensity, scheduling, cell-cycle specificity
  2. Tumour
    eg resistance, stage, anatomic site, blood supply
  3. Patient
    eg drug tolerance, renal, hepatic function
33
Q

Drug related factors (4)

A
  • PK (ADME)
  • drug distribution to the tumour microenvironment
  • MOA (cell cycle specificity)
  • combination therapy
34
Q

Combination therapy to overcome __ (3)

A
  1. Sensitivity
    - tumours may be non-responsive at normal clinical achievable doses
  2. Toxicity
    - avoid the use of high doses cos use lower dose of each drug compared to monotherapy
  3. Resistance
35
Q

Desirable characteristics for combination therapy (6)

A
  1. Each agent must have >20% response rate when used alone
  2. Different dose limiting toxicities
    - prevent additive toxicity
  3. Should not antagonise each other
    eg vinca alkaloids & taxanes
  4. Each agent should be given in a dose equivalent to that used when monotherapy
  5. Different pharmacological action
    - increase MOA, increase chance of eliminating tumours
  6. Increase overall intensity of therapy
36
Q

Tumour related factors (5)

A
  1. Tumour growth kinetics
  2. Tumour size
  3. Site of tumour
    - sanctuary sites (eg testis & CNS)
  4. Tumour vascularisation
    - large tumours have central necrosis due to poor blood supply
  5. Tumour cell heterogeneity (resistance)
    - Goldie-Coldman hypothesis
    - developing resistance is a multi-step event
37
Q

Small tumours

A
  • high growth rate
  • chemotherapy most active against
  • early detection/screening impt so can initiate chemotherapy agents early
38
Q

Large tumours

A
  • most cells are not proliferating & less likely to be killed by chemotherapy agents
39
Q

Increasing tumour size & risks (3)

A
  • greater probability of metastasis
  • greater probability of drug-resistant cells
  • poor drug distribution
40
Q

Patient related factors (5)

A
  1. Patient’s overall health status
  2. Immunocompetency
  3. Organ function
  4. Treatment history
    - cumulative dose limiting toxicities
  5. Patient’s age
41
Q

Patient’s overall health status measurements (2)

A
  1. Karnofsky Performance Status Criteria (subjective measure)
    - increase percent means increase function/activity
  2. ECOG Performance Status
    - grade 0-4
    - increase grade means increase disability
42
Q

Immunocompetency (3)

A
  • impaired cell-mediated immunity is a poor prognistic factor
  • disease progression & anti-cancer therapies collectively impair immune system
  • use of immunosuppressants for minor ailments also impair immune system eg corticosteroids
43
Q

Organ function (5)

A
  • most chemotherapy are eliminated hepatically or renally
  • determine drug clearance and possible accumulation of toxicities
  • functional monitoring is essential before & during treatment
  • monitor for signs & symptoms of toxicity
  • empirical dose adjustment
44
Q

Treatment history (2)

A
  1. Cumulative toxcities
    - toxicities from past treatment have cumulative toxicities
    eg myelosuppression leading to life-threatening aplasia
    - affects dose & scheduling of chemotherapy to avoid life-threatening aplasia
  • *Resistance
  • if recent chemo use and still relapse, likely resistance development
  • tumour factors NOT patient factors
45
Q

Patient’s age (4)

A
  • myelosuppression recover more slowly among older patients
  • controversial issues regarding resilience to chemotherapy in elderly patients
  • can initiate chemo if overall health ok
  • consider concomitant diseases
46
Q

Curative vs Palliative (3)

  • intense short term ADR
  • long term ADR
A

Curative

  • reduction in intensity are accepted only for compelling reasons
  • intense short term but reversible toxicity is acceptable if there are no other alternatives
  • long term permanent toxicities to be avoided where possible

Palliative

  • aim is to improve quality of life
  • intense short term toxicity is undesirable
  • long term toxicities are generally not a consideration (avoid)
47
Q

Palliative chemotherapy (3)

A
  • control residual disease/metastases &
  • reduce existing cancer symptoms (eg pain, obstruction)
  • may be used together with surgery &/or radiotherapy
48
Q

Neoadjuvant vs Adjuvant chemotherapy

A

Neoadjuvant

  • administered before surgery to “debulk” the tumour, reducing the extent & disfigurement of surgery
  • eradicate micrometastases

Adjuvant

  • to eradicate any residual micrometastases & prevent them from growing into clinically evident disease
  • used together with surgery/radiotherapy (after)
49
Q

Factors affecting choice of chemotherapy agents (4)

A
  1. Types of tumours, stage & rate of growth
  2. Patient factors (age, organ function, health status)
  3. Costs
  4. Availability
50
Q

Treatment evaluation (5)

A
  1. Response rate
  2. Duration of response
  3. Duration of survival
  4. Toxicities associated with treatment
  5. Impact on quality of life
51
Q

Response rate measurement (2)

A
  • reflects the % of patients who had tumour regression following therapy
  • types :
    1. Complete Response (CR)
  • for at least 1 month
    2. Partial Response (PR)
  • at least 50% decrease of measurable tumour
  • no new area of disease & no evidence of progression
    3. Disease Progression (DP)
  • increase >25% of measurable tumour
    4. Stable Disease (SD)
    5. Overall response rate (CR+PR)
    6. Clinical benefit (CR+PR+SD)
52
Q

Duration of response measurement (2)

A
  • time from the first documentation of response to the recurrence or progression of the tumour
  • types :
    1. Time to disease progression
    2. Disease free interval time
53
Q

Measurement of survival

A

Overall survival rate

- proportion of patients surviving for a defined period of time

54
Q

Measurement of toxicities associated with treatment

A

Common Toxicity Criteria (CTC)

  • grade 0 to 5
  • 0 means non-severe
  • 5 means most severe (death releated)
55
Q

Karnofsky Performance Status (2)

  • 0%
  • 20%
  • 60%
  • 100%
A
  • measure of the level of activity of which the patient is capable of
  • range from 0-100%

0% means dead
20% very sick, require hospitalisation & active supportive treatment
60% require occasional assistance
100% means normal function

56
Q

ECOG Perfomance Status

A
  • measure of level of activity of which the patient is capable of
  • grade 0 to 4

0 means fully active (normal function)
4 means completely disabled

57
Q

Hematological toxicities

A
  • objective signs (eg neutropenia)

- clear guidelines to withhold or delay treatment

58
Q

Non-hematologica toxicities

A
  • subjective signs & symptoms

- individual threshold varies & determine withhold or delay treatment

59
Q

Measurement of impact on quality of life (2)

A
  1. Karnofsky Performance Status

2. ECOG Perfomance Status

PR3136 (19 decks)

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