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Sita CP > Lecture 19: Principles of Cancer Therapy > Flashcards

Lecture 19: Principles of Cancer Therapy Flashcards

1
Q

How clinically relevant is cancer?

A

cancer is common clinical problem in NZ
- 21050 new cancer registrations
- 8,891 cancer deaths
- cancer as a disease and cancer deaths are legally required to be notified to MOH. This provides robust national statistics
- cancer causes mortality on a large scale
(every day in auckland 5 people die from cancer and 10 are diagnosed)

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2
Q

Top 5 cancers in NZ

A
  1. prostate
  2. colon, rectum and anus
  3. breast
  4. melanoma of skin
  5. trachea, bronchus, lung
    = total to 65% of all cancer burden in NZ
    - same cancer management principles for common and uncommon cancer types
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3
Q

Clinical Presentations of cancer

A
  1. Primary Tumour
  2. Metastasis
  3. Paraneoplastic syndromes
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4
Q

Primary tumours

A
  • 1x malignant cells proliferates and destroys/compromises surrounding tissues
    LOCAL effects due to:
    1. Expansion (mass)
    2. Breach of epithelial surfaces (bleeding) e.g. haemoptosis if breach lung epithelium
    3. Narrowing of body tubes (bowel obstruction) can cause infection
    4. Invasion of local structures (hoarseness) invades into mediastinum and impinge of recurrent laryngeal nerve
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5
Q

Metastasis

A

DISTANT effects involving:

  1. lymph nodes (mass)
  2. lungs (breathlessness) due to multiple metastatic lesions
  3. brain (headache and vomiting) due to brain mets
  4. liver or bone (localised pain)
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6
Q

Paraneoplastic syndrome

A

GENERALISED effects due to:

  1. Hormonal (hypercalcemia)
  2. Autoimmune (myasthenia gravis)
  3. Undefined mechanisms (finger clubbing)
    e. g. germ cell tumour producing Beta-CG as are indirectly involved with cancer process, causing gynecomastia (breast development)
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7
Q

What are the principles of Cancer Diagnosis and Investigation

A
  1. Diagnosis
  2. Staging
  3. Functional Assessment
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8
Q

Diagnosis of cancer

A

Pathological diagnosis, requiring tumour biopsy and histopathology, in order to exclude benign pathology, identify tissue of origin, tumour grade and prognostic markers
Note: pathological diagnosis, as may look like cancer but isnt always

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9
Q

Staging of cancer

A

Determination of extent of involvement (spread) according to staging systems (TNM system)

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10
Q

Functional assessment of cancer

A

Assessment of how patients are likely to cope with the disease and treatment
e.g. w. lung cancer resectional surgery, need to carry out extensive lung function testing to see if will survivie

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11
Q

Principles of Cancer Treatment

A
  1. Key Questions:
    a) Is surgical resection or curative treatment possible (Radical treatment is justified)? Or will benefits of surgery just be for palliative purposes to maximise quality of life and survival extension?
    b) What treatment modalities are required for the best outcome? Chemo, radiotherapy, surgery (individually or together)
    c) Are different treatment options available? (mastectomy (whole breast removal) vs lumpectomy (small resection) + radiotherapy
    - cosmetic outcome differences
    - different components of treatment
  2. Multidisciplinary approaches usually required
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12
Q

What are the Principles of Cancer surgery

A
  1. Cure:
    - Surgery is the most effective treatment for curing cancer (>40% of cancer is cured by surgery)
    - Complete excision + margin of normal tissue
  2. Other indication:
    - Diagnosis (excision biopsy)
    - Staging (assess local lymph node spread) e.g. breast cancer from axillary lymph nodes
    - Local control
    - Palliation (bypass obstruction)
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13
Q

What are the Principles of Radiation Therapy?

A
  1. Controls cell death via Ionising radiation: radiation energy damages DNA + generates free radicals from water, these damage membranes, proteins and organelles
  2. Therapeutic radiotherapy:
    - External beam radiotherapy
    - Planned according to: a) treatment fields/exposed areas, b) Dose to tumour and normal tissue, c) number of treatment fractions
    - Is a component of curative treatment (e.g. head and neck cancer, cured via local radiotherapy and chemo combo)
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14
Q

What are the Principles of Cancer Chemotherapy?

A

Chemo definition: Use of chemical to kill disease causing cells in the body (e.g. bacteria, fungi, viruses and cancer)
-ideally wouldnt effect normal body processes
vs
Drug Therapy which uses chemicals to modulate body processes e.g. arterial blood pressure w. antihypertensives and mood with antidepressants
- goal is to achieve selective toxicity

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15
Q

What is the goal of cancer chemotherapy

A

Selective toxicity

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16
Q

Selective toxicity

A

goal of cancer chemotherapy

Selective toxicity occurs when there is toxic effects int he cancer cells, w/o / less effects in the host cells

17
Q

How is Selective toxicity achieved?

A

Via exploiting differences b/w normal host cells + disease producing cells

  1. Unique target in pathogen (penicilin can only attack bacterial cells, as they have cell walls and out normal host cellsonly have cell membrane)
  2. Structurally different target in pathogen (di-hydrophilic reductase is present in both normal host cells and disease cells, but has a different structure in disease cells)
  3. Functionally different target in host
18
Q

Therapeutic Index (TI)

A

important indicator of selective toxicity
Therapeutic index = ED50 Unwanted toxicity / ED50 for therapeutic activity
TI is the Ratio of dose required to produce a toxic effect / dose required to produce desired effect
High TI = large dose required to achieve unwanted toxicity = greater selective toxicity
Low TI = small difference b/w unwanted toxicity and therapeutic activity = not much selective toxicity

19
Q

Pharmacodynamics of cancer chemotherapy

A

Relationship b/w drug concentration and drug effect as a log curve
Early: low concentration has no effect
Middle: large increase of drug effect with increasing concentration
Late: plateau: no further increase in drug effect no matter how much concentration increases

20
Q

Classifications of Cancer chemotherapy drugs according to mode of Action

A
  1. Alkylating agents (binds DNA) e.g. cyclophsophamide
  2. Platinum based drugs (binds DNA) e.g. cisplatin
  3. Antimetabolites (inhibits DNA synthesis) e.g. methotrexate
  4. Topoisomerase-interactive drugs (inhibit topoisomerases) e.g. doxorubicin
  5. Antimicrotubule drugs (bind microtubules, which form the spindle in mitosis) e.g. paclitaxel
  6. Hormonal agents (block production or action of sex steroids) e.g. tamoxifen (oestrogen receptor agonist for breast cancer)
  7. Targeted therapies (block oncogenes) e.g. imatinib ( blocks bcl-acl oncogenic protein of chronic myeloid leukemia)
  8. Vascular targeting therapies (inhibit angiogenesis) e.g. bevacizumab (new blood vessel development in tumours)
21
Q

What are the First order kinetics of tumour cell growth and chemotherapy killing?

A
  1. Tumour growth first order kinetics: Starts with on malignant cell –> divides with constant doubling time –> clinical evidence at 10^8 cells –> lethal at 10^12 cells
  2. Chemotherapy killing first order kinetics: Each dose kills a constant proportion of tumour cells –> therefore repeated doses are required –> and must continue after clinical disappearance of disease
22
Q

Model of tumour growth and response to treatment

A

**graph
Show that 10^12 would be lethal burden of cancer cells
treatment steps are identical
complete tumour treatment, but must continue therapy so can eradicated the millions of cancer cells still present in the body

23
Q

Criteria for Combination Chemotherapy

A

Combination chemo is more effective that just using a single agent
Criteria:
1. Some activity as a single agent
2. differing mechanisms of action
- trying to increase the toxicity of drug, through different ways and mechanisms (dont want same mechanism of action, as might as well just increase the dose of first drug instead of using 2x drugs which do the same thing.)
3. different side effect profiles
- avoids overlapping major form of toxicity, which could burden the effected organ system/tissue

24
Q

BEP example of combination therapy for testicular cancer

A
  1. Bleopycin: induces DNA breaks in the lung
  2. Etoposide: poisons topoisomerase II in bone marrow causing cytopenias
  3. cisPlatin: induced DNA cross links in peripheral nerves
    Note: all of these chemo drugs work through their individual action, through a different mechanism and with different side effect profiles
25
Q

Features of adverse effects to cancer chemotherapy?

A

Adverse effects to chemo are common, and are mainly due to the pharmacological action of the drug
The extent of the adverse effects due to chemo determine the dose and dosing interval of the chemotherapy treatment itself
The adverse effects may be annoying, dangerous. they might also limit patient’s compliance with their therapy
Most adverse effects due to chemo (e.g. nausea and vomitting) are reversible or clinically manageable

26
Q

Examples of adverse effects of cancer chemotherapy (due to their pharmacological mechanism)

A
  1. Antiproliferative: myelosupression, mucositis, alopecia and sterility (inhibition of proliferation of cells in tumours and systems with high levels of proliferation) e.g. mucosa of the gut (ulcers), hair follicles (baldness), gonads, bone marrow (cytopenia)
  2. Mutagenesis: Second cancers and teratogenecity (can kill and potentially cause cancer and cuase damage to the uterus)
  3. Microtubule disturbance: peripheral nerve toxicity (as microtubules are important in transporting the long axon of peripheral and central nerves)
  4. Sex steroid deficiency: can cause decreased libido, impotent and flushing
27
Q

Indications for Cancer Chemotherapy

A
  1. Cure: high cure rates achieved in acute lymphoblastic leukemia (most common child cancer), testicular cancer (most common in 15-35 r old boys) and hodgkins disease ( youthful cancers. 80-90% cure rate)
  2. w. Surgery: adjuvant chemotherapy, for node-positive breast cancer + colorectal cancers
  3. w. radiotherapy: combined modality therapy, for head&neck, cervical cancer etc.
  4. w. palliation: improve symptoms and survival time (e.g. lung cancer, where complete cure isnt a realistic probability)
28
Q

Examples of local pathology, paraneoplastic syndrome and metastatic spread

A

local pathology: haemoptosis
paraneoplastic syndrome: finger clubbing
metastatic spread: back pain

29
Q

Oncologu clinical case

A 
Had a CT guided needle biopsy
Then a pathological diagnosis
Then had staging CT scans
1. Assessment summary
2. Treatment plan
X-ray to see response to therapy

Sita CP (9 decks)

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