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Pharmacotherapeutics > Principles of Cancer Treatment (Part 1) > Flashcards

Principles of Cancer Treatment (Part 1) Flashcards

1
Q

Describe tumour growth kinetics

A
  1. logarithmic: once detected, grows quickly
  2. tumour growth is in equilibrium: slope of the curve depends on ratio of cell division to cell loss, doubling time, growth fraction
  3. past 30 generations, clinical symptoms show and there is exponential cell growth
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2
Q

What is doubling time, and is doubling time consistent throughout all types of cancers?

A
  • 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.
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3
Q

When does a tumour metastasise and how does it metastasise?

A
  1. Before clinically detectable, and when it is clinically detectable
  2. 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.
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4
Q

What are the goals of cancer treatment?

A
  • curative
  • prolong quality and duration of life
  • symptom relief (palliative treatment)
  • clinical trials and experimental therapies
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5
Q

What are the characteristics of ideal cancer treatment?

A
  • safe, effective and discriminating
  • actions should be limited to cancer cells
  • should have few side-effects
  • should return patient to former state of health
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6
Q

Surgery characteristics

A
  • oldest cancer treatment
  • curative for localised disease
  • commonly used to remove primary cancer or metastatic masses
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7
Q

What is surgical debulking?

A
  • pain or symptom relief

- reduce size of tumour to increase efficacy of other therapies (radiotherapy, chemotherapy etc.)

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8
Q

Radiation therapy

A
  • 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.
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9
Q

How is radiation therapy delivered and expressed (units-wise)?

A

by external beam and brachytherapy
expressed in Gray (Gy)
- typical dose for glioma: 60Gy
- typical dose for breast cancer: 50Gy

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10
Q

What is the dose-limiting factor for radiation therapy?

A

Normal tissue damage

  • early effects to rapidly dividing tissues
  • late effects in organs
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11
Q

Serious radiation toxicities:

  1. bone marrow
  2. liver
  3. stomach
  4. intestine
  5. rectum
  6. brain, CNS
  7. lung
  8. fetus
A
  1. anemia
  2. hepatitis
  3. ulcer / hemorrhage
  4. ulcer / perforation
  5. ulcer / stricture
  6. infarct / necrosis
  7. pneumonitis / fibrosis
  8. death
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12
Q

How is palliation of pain achieved through radiotherapy?

A
  • external beam

- strontium-89

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13
Q

Chemotherapy

A
  • most useful for treatment of systemic or disseminated disease (including micrometastases)
  • used as adjunct to surgical/radiotherapy and palliation
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14
Q

Basic principles of chemotherapy

A
  1. Drug kills a constant proportion of tumour cells rather than a constant number of cells (first order kinetics).
  2. It has the greatest effect on cells that are actively dividing.
  3. Drugs have a narrow therapeutic index, treatment is. a balance between efficacy and toxicity
  4. Combination therapy can be used to increase treatment outcome.
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15
Q

Drug kills a constant proportion of cells rather than a constant number of cells.

A
  • 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.
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16
Q

Drugs have narrow therapeutic index, hence treatment is a balance between efficacy and toxicity.

A
  1. Tolerance
    Cure - high
    Extend life - moderate
    Palliate symptoms - low
  2. Special concerns
    Cure - delayed and late side effects
    Extend life - value of added time
    Palliate symptoms - symptoms control
  3. 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
17
Q

What are the advantages and disadvantages of combination therapy?

A

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
18
Q

Application of basic principles of chemotherapy

  1. Drug kills a constant proportion of tumour cells rather than a constant number
  2. It has the greatest effect on cells that are actively dividing
  3. Drugs have a narrow therapeutic index, thus treatment is a balance between efficacy and toxicity.
  4. Combination chemotherapy can be used to improve treatment outcome
A
  1. Repeat treatment cycles
  2. Treat ASAP, when the disease is in the early stage
  3. Know intent of treatment, monitor for side effects
  4. Where possible
19
Q

What is the protocols concept?

A
  • different tumours respond to different cocktails of chemotherapy
  • efficacy is established through clinical trials
  • different centres have different protocols of treatment
20
Q

What is the AC protocol for breast cancer?

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

What is the FOLFIRI colon protocol (weekly)?

A
  • 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
22
Q

What are the paclitaxel and carbo+gemzar lung protocols?

A
  • 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
23
Q

How are doses administered?

A

based on BSA

BSA (m2) = square root of (weight x height) / 3600

24
Q

How to intensify the doses?

A
  • increase the number of doses

- reduce the interval

25
Q

Selection of chemotherapy treatment algorithm:

A
  1. Determine histological diagnosis, tumour staging and other prognostic variables
  2. Identification of treatment option and benefit
  3. Assessment of comorbid conditions and psycho-social environment
  4. Determine treatment-related risks
  5. Assessment of risk versus benefit
  6. Selection of therapeutic regimen

Pharmacotherapeutics (28 decks)

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