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PR3136 > Principles of cancer treatment > Flashcards

Principles of cancer treatment Flashcards

1
Q

What is TD

A

Doubling Time: Time taken for tumour to double its mass, varies among different tumour

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2
Q

Two main pathways of metastasis

A
  1. Blood

2. Lymphatic system

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3
Q

Describe the Mechanism of Tumour cell metastasis

A
  • Tumour cell release lytic enzyme, causing basement membrane to dissolve
  • Invade and move through defect due to increased motility and decreased cell-cell adhesiveness
  • Tumour then bind to basement membrane through mediation of altered receptors on cell surface
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4
Q

Two key properties of tumour growth

A
  1. Growth is logarithmic

2. Once detectable, tumour appears to grow quickly

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5
Q

Factors affecting Tumour Growth Kinetics

A
  1. Vasculature
  2. Presence of other cell populations
  3. Space restrictions
  4. Necrosis
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6
Q

On the Gomperzian Growth Curve, what affects the slope of the curve?

A
  1. Ratio of cell division to cell loss
  2. Growth fraction
  3. TD
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7
Q

What is “Silent Cancer”

A

Tumour at undetectable levels but rapidly growing

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8
Q

Common metastatic sites

A
  1. Liver
  2. Lung
  3. Lymph
  4. Bone
  5. Brain
  6. Skin
  7. Adrenal Glands
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9
Q

Goals of Cancer Therapy

A
  1. Curative
  2. Maintain quality and duration of life
  3. Sx relief, if uncurable
  4. Clinical Trials for experimental therapies
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10
Q

Characteristics of Ideal Cancer Treatment

A
  1. Safe, effective, discriminating (like abx)
  2. Actions only limited to cancer cells
  3. Few SE
  4. Curative
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11
Q

List the three types of cancer treatment and briefly describe their purpose

A
  1. Surgery: Debulking
  2. Radiation
  3. Chemotherapy: For systemic or disseminated diseases, including micrometastases, as adjunct to surgery/radiotherapy and palliation
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12
Q

Dose-limiting factor of radiation therapy. Hence what is its effectiveness to different tissue?

A

Damage to normal tissue

  • Early effects to rapid dividing tissues
  • Late effects in organs
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13
Q

Describe the three basic principles of Cancer Chemotherapy

A
  1. Drug kills via first order kinetics (constant proportion)
  2. Drugs have narrow TI: Must balance between toxic and efficacy
  3. Combination chemo can be used to improve tx outcome
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14
Q

Distinguish between resistance and relapse in Chemotherapy treatment

A
  • Resistance: Chemotherapy initially effective, but tumour cell levels never fall below clinical detection
  • Relapse: Tumour cell levels fall below limit of detection. When chemotherapy stops, tumour levels bounces back to detectable levels
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15
Q

What do each of the principle of Cancer Chemotherapy imply about cancer treatment?

A
  1. Constant proportion killing:
    - Treatment when tumours are small gives better result
    - Chemo greatest effect on actively dividing cells
    - Repeat treatment cycle
  2. Narrow TI:
    - Decreasing tolerance and challenges to cure, extend life and palliate sx
    - Always know intent of treatment and hence adjust the intensity
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16
Q

Advantages and Disadvantages of Combination Chemotherapy

A

Advantages:

  • Increase killing within acceptable toxicity
  • Broadened coverage
  • Slow emergence of resistance

Disadvantages:

  • Multi toxicities = more discomfort
  • Complicated to administer
  • Impact of dose effect (e.g. titration of dose = get intended effect?)
  • More Expensive
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17
Q

Describe the Protocols concept in Chemotherapy

A
  • Different cocktails of chemo for different tumours
  • Efficacy established via clinical trials
  • Different centres have different protocols for treatment
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18
Q

How is dosing of chemo usually expressed and why is it expressed that way

A

Almost always: unit weight/body surface area (BSA) (e.g. 60mg/m2)

Reason: BSA is more closely correlated with cardiac output, which determines blood flow to liver and kidney, and subsequently influences drug elimination

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19
Q

Formula for BSA

A

Sqroot (Weight x Height / 3600)

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20
Q

A Chemo Protocol orders for:

  • IV Doxorubicin 60mg/m2, day 1
  • IV Cyclophosphamide 600mg/m2, day1
  • Repeated every 21 days

What are the two reasons
on why repeated doses spaced so far apart?

A
  1. Achieve optimal therapeutic benefit with minimal toxicity

2. “Drug rest” to allow normal cells to recover

21
Q

Define dose intensity. What are the ways to intensify dosing regimen of a chemo protocol?

A

Dose intensity is the amount of drug given per unit time, and has profound influence on treatment outcome.

Ways to intensify:

  1. Reduce interval between repeated doses
  2. Increase the dose of each administration
22
Q

What are the factors affecting the selection of Chemotherapy Regimen?

A
  1. Histological documentation of tumour type
  2. Stage of disease
  3. Prognostic variables
  4. Patient-related variables
  5. Toxicities
  6. Risk vs Benefits
23
Q

Describe the general algorithm for treatment that leads to selection of therapeutic regimen for cancer

A
  1. Determine histological dx, tumour staging, prognostic variables
  2. Identify tx and determine benefit
  3. Assess comorbid conditions and psycho-social environment
  4. Determine tx risk
  5. Assess risk vs benefit
  6. Select therapeutic regimen
24
Q

The three broad factors that affects response to chemotherapy

A
  1. Drug
  2. Tumour
  3. Patient
25
Q

Describe the Drug-related factors that affect response to chemotherapy

A
  1. Drug PK: distribution to tumour microenvironment
  2. MoA and cell cycle specificity
  3. Different effect in combination chemotherapy
26
Q

What problems are combination chemotherapy used to overcome?

A
  1. Sensitivity: overcome non-responsiveness of tumours at clinically achievable monotherapy doses
  2. Toxicity: avoid high doses to minimise toxicity
  3. Resistance: Inherent genetic instability leads to non-random mutation conferring resistance

[Slides 45-47 for illustrations]

27
Q

What are some mechanism of resistance to drugs developed by tumour cells? Name one example of each mechanism

A
  1. Decrease cellular uptake/ increase drug efflux: MTX
  2. Increase ability to repair DNA: DNA damaging drugs
  3. Decreased drug activation: Ara-C
  4. Increased drug degradation: Ara-C
  5. Alternate biochemical pathways: Ara-C
28
Q

What are some desirable characteristics of the chemo agents used in combination therapy?

A
  1. Must be effective (>20% response rate)
  2. Different dose-limiting toxicities
  3. Should not antagonise each other
  4. Give in a dose equivalent to that used when agent is given alone
  5. Have different pharmacological action
29
Q

List the Tumour-related factors that affect response to chemotherapy

A
  1. Tumour growth kinetics
  2. Tumour size
  3. Site of tumour and tmour vascularisation
  4. Tumour cell Heterogeneity - Resistance
30
Q

Describe how Tumour Growth Kinetics affect the response to chemotherapy

A
  • When tumour is small with high growth fraction, chemo is most successful
  • Highlights the importance of early detection/screening programs
31
Q

Describe how a large Tumour Size affect the response to chemotherapy

A

Large tumour means that cells are not proliferating, hence less likely killed by chemo

The larger the tumour:

  1. Greater probability of metastasis
  2. Greater probability of drug-resistant cells
  3. Poor drug distribution to tumour microenvironment due to lack of blood vessels
32
Q

Describe how the site of Tumour and its vascularisation affect the chemotherapy regimen that will be used

A
  1. At Sanctuary sites like CNS at Testis:
    - Drug penetration poor
    - Require higher dose, or special administration
  2. With tumour at necrotic sites (esp. large tumour):
    - Poor vascularisation = difficult for drug to reach tumour
33
Q

What is the Goldie-Coldman hypothesis?

A

It describes how tumour cells develop resistance to chemo via random mutation

  1. Tumour cells are genetically unstable = reporudce inconsistently = clones with different characteristics
  2. For drug therapy, the tumour cells are “moving target” hence some tumour cells may be resistant
34
Q

Describe the Patient-related factors that affects the response to chemotherapy

A
  1. Overall Health status
    - ECOG/Karnofsky Perf Status Criteria help guide treatment decisions
    - Chemo attenuated only in deadly toxicities to maintain full anti-tumour activity
  2. Immunocompetency
    - Impaired immunity is poor prognostic factor
    - Disease progress, chemo & immunosuppressants collectively impair immune system
  3. Organ (Renal and liver func)
    - Impaired = reduced elimination of drugs = increased systemic toxicity
    - Dose reduction often empirical
  4. Tx history (prior chemo/radio tx)
    - Tx history affect major organ toxicity
    - Anticancer drug cause cumulative myelosuppression, which is a major dose-limiting toxicity of anticancer drugs
  5. Patient age (controversial)
    - To factor concomitant disease
35
Q

Distinguish between how chemo therapy is used in curative vs palliative

A

Curative:

  • Reduce intensity only for compellling reason
  • Intense short term, but reversible toxicity is acceptable
  • Long term toxicities avoided if possible

Palliative:

  • Improve QoL: Intense short term toxicity undesirable
  • Long term toxicity not considered
36
Q

What is “Neoadjuvant” chemotherapy

A
  • Tx given before surgery to debulk tumour to reduce extent and disfigurement of surgery.
  • Also helps eradicate micro-metastases
37
Q

What is “Adjuvant” chemotherapy

A
  • Systemic therapy
  • To eradicate residual micro-metastases and prevent them from growing into clinically evident disease
  • Usually used with surgery and/or radiotherapy
38
Q

What is “Palliative” Chemotherapy

A
  • Systemic therapy to control residual disease/metastases and reduce existing cancer sx like pain and obstruction
  • May be used with surgery/radiotherapy
39
Q

What are other factors affecting choice of treatment between surgery, radio and chemo?

A
  1. Type of tumour, stage and rate of growht
  2. Patient: Age, organ function and performance status
  3. Cost
  4. Availability
40
Q

What are some factors considered in evaluating cancer treatments?

A
  1. Response rate
  2. Duration of response
  3. Duration of survival
  4. Toxicities associated with treatment
  5. Impact on QoL
41
Q

Describe the parameters of response rate that are involved in the assessment of cancer treatment

A
  1. Complete response (CR): Complete disappearance of clinical evi of tumour for ≥1 months with retunr of performance status
  2. Partial Response (PR): ≥50% decrease in measurable tumour. No new area of disease and progression
  3. Disease Progression (DP): increase of measurable tumour by >25% (since tx initiation). May have new lesion or tumour-induced death
  4. Stable disease (SD): Measurable tumour that does not meet any of the above. Tumour does not increase/decrease in size by >25% since tx initiation
42
Q

What are the equations to calculate response ratethat help assess cancer treatment

A
  1. Overall response rate/ Objective response rate = CR + PR

2. Clinical Benefit = CR + PR + SD

43
Q

What is “duration of response” in assessing cancer treatment?

A

Time from first documentation of response to recurrence or progression of tumour:

  1. Time to disease progression
  2. Disease free interval time
44
Q

What is the duration of response for patients who had CR?

A

Disease-free survival time

45
Q

Describe the parameters that measures survival and are involved in the assessment of cancer treatment

A
  1. Survival rate: Proportion of patients surviving for defined time after tx
  2. Median Survival Rate:
    - Time from dx, tx or documented response till time when 50% patients died
  3. Duration of survival: The time that a patient or group of patients lives after specific event
  4. Disease Free Survival Time: Time from CR till disease recurs, or patient dies w/o evi of disease
46
Q

Three broad categories of toxicities associated with cancer tx

A
  1. Dose limiting toxicity
  2. Hematological toxicities
  3. Non-hematological toxicities
47
Q

What tool or measurement is used to measure toxicities of cancer tx?

A

Common Toxicity Criteria (CTC) and CTC Adverse Events (CTCAE)

48
Q

What are the tools to measure baseline performance status of patient, such that toxicities can be compared?

A
  1. Karnofsky Performance Status (KPS): In terms of %
  2. ECOG Performance Status: In terms of Grading
    - Both KPS and ECOG can be compared with each other

PR3136 (18 decks)

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