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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
Reasons for protocols (4)
- 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
Calculation for dose of chemotherapy is based on __
Body Surface Area (BSA)
27
BSA formula
square root [(height + weight)/3600] height in cm BSA in m^2
28
Why is BSA used to calculate dose?
- 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
Importance of "drug rest" (2)
- to allow for normal cells to recover | - achieve optimal therapeutic benefit with minimal toxicity
30
How to intensify dose? (2)
1. Reduce dosing interval | 2. Increase the dose
31
Selection of chemotherapy regimen steps (6)
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
Factors affecting response to chemotherapy (3)
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
Drug related factors (4)
- PK (ADME) - drug distribution to the tumour microenvironment - MOA (cell cycle specificity) - combination therapy
34
Combination therapy to overcome __ (3)
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
Desirable characteristics for combination therapy (6)
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
Tumour related factors (5)
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
Small tumours
- high growth rate - chemotherapy most active against - early detection/screening impt so can initiate chemotherapy agents early
38
Large tumours
- most cells are not proliferating & less likely to be killed by chemotherapy agents
39
Increasing tumour size & risks (3)
- greater probability of metastasis - greater probability of drug-resistant cells - poor drug distribution
40
Patient related factors (5)
1. Patient's overall health status 2. Immunocompetency 3. Organ function 4. Treatment history - cumulative dose limiting toxicities 5. Patient's age
41
Patient's overall health status measurements (2)
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
Immunocompetency (3)
- 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
Organ function (5)
- 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
Treatment history (2)
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
Patient's age (4)
- 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
Curative vs Palliative (3) - intense short term ADR - long term ADR
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
Palliative chemotherapy (3)
- control residual disease/metastases & - reduce existing cancer symptoms (eg pain, obstruction) - may be used together with surgery &/or radiotherapy
48
Neoadjuvant vs Adjuvant chemotherapy
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
Factors affecting choice of chemotherapy agents (4)
1. Types of tumours, stage & rate of growth 2. Patient factors (age, organ function, health status) 3. Costs 4. Availability
50
Treatment evaluation (5)
1. Response rate 2. Duration of response 3. Duration of survival 4. Toxicities associated with treatment 5. Impact on quality of life
51
Response rate measurement (2)
- 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
Duration of response measurement (2)
- 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
Measurement of survival
Overall survival rate | - proportion of patients surviving for a defined period of time
54
Measurement of toxicities associated with treatment
Common Toxicity Criteria (CTC) - grade 0 to 5 - 0 means non-severe - 5 means most severe (death releated)
55
Karnofsky Performance Status (2) - 0% - 20% - 60% - 100%
- 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
ECOG Perfomance Status
- 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
Hematological toxicities
- objective signs (eg neutropenia) | - clear guidelines to withhold or delay treatment
58
Non-hematologica toxicities
- subjective signs & symptoms | - individual threshold varies & determine withhold or delay treatment
59
Measurement of impact on quality of life (2)
1. Karnofsky Performance Status | 2. ECOG Perfomance Status

PR3136 (19 decks)

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