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BIOM2070 > Therapeutics of chemotherapy > Flashcards

Therapeutics of chemotherapy Flashcards

1
Q

Anaplasia

A

loss of structural organisation and useful function of a cell.

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2
Q

Dysplasia:

A

disturbance in the size, shape and organisation of cells and tissues.

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3
Q

Hyperplasia

A

increase in the number of cells in a tissue or organ causing increase in the bulk of an organ.

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4
Q

Neoplasm

A

abnormal growth of tissue whose cells usually have rapid growth. Neo means “new” and plasma means “formation”.

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5
Q

Benign

A

is non-malignant and suggests that such tumours are harmless. However, some benign tumours can cause death of tissue and can lead to malignancy.

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6
Q

Malignant:

A

means to have the property of local invasion, destructive growth and potentially metastasis

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7
Q

Carcinomas

A

(~85% of cancers) – occur in the epithelium (lining of organs and skin)

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8
Q

Sarcomas

A

(~6% of cancers) – form in the connective tissues of the body (muscle and bone)

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9
Q

Leukaemias/Lymphomas

A

(~5% of cancers) – occur in the bone marrow and lymphatic system

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10
Q

Other forms of cancer

A

(~4%) – brain tumours and other rare forms of cancer

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11
Q

Cancer treatments are variable and depend on numerous factors some of which include:

A

Type of cancer

Location of cancer

Stage of cancer and intended clinical end point
(can we cure?)

Health status of patient (age, quality of life, preference)

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12
Q

Treatments are divided into different categories based on their goal and mechanism of action (MOA)

A

Surgery

Radiation

Chemotherapy

Targeted therapy

  • hormonal
  • biological response modifiers
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13
Q

Adjuvant therapy:

A

Additional cancer treatment given after the primary treatment to lower the risk that the cancer will come back. Adjuvant therapy may include chemotherapy, radiation therapy, hormone therapy, targeted therapy, or biological therapy.

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14
Q

Neo-adjuvant therapy:

A

Treatment given as a first step to shrink a tumour before the main treatment, which is usually surgery, is given. Examples of neoadjuvant therapy include chemotherapy, radiation therapy, and hormone therapy.

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15
Q

Combined modality:

A

The use of drugs with other cancer treatments (radiation therapy or surgery).

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16
Q

Palliative

A

is given without curative intent, but simply to decrease tumour load and increase life expectancy.

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17
Q

Chemotherapy can be used for different reasons:

A
  1. As a cure or to achieve remission
  2. To help other treatments (neo-
    adjuvant or adjuvant chemotherapy)
  3. To control the cancer and provide symptom relief (palliative chemotherapy)
  4. To prevent or delay the cancer returning
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18
Q

CALCULATING CHEMOTHERAPY DOSES

A

Majority of chemotherapy doses are individualized according to patient Body Surface Area (BSA) to give maximal anti-tumour effect with acceptable levels of toxicity.

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19
Q

To prepare for chemotherapy and between cycles, patients often have a number of other tests to plan treatment. These may include:

A

 Kidney, liver function and full blood tests
 X-Rays and scans are conducted to ensure the patient is fit for treatment and to review how the cancer is responding to treatment
 Heart monitoring tests (such as ECGs and ECHOs) may be conducted to see if the drugs are affecting the patient’s heart
 Lung function tests may be conducted to check the effect of some chemotherapy drugs on the patient’s lungs

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20
Q

Choice of chemotherapy

A

 Choice of treatment is based on the type of cancer cells, rate at which they divide, time at which a given drug is likely to be effective and the time it takes for normal cells that are affected to repair themselves
• This allows for balance between cancer cell death and normal cell recovery

Combination therapy increases the elimination of cancer cells since different drugs affect cancer cells at different points in the cell cycle

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21
Q

Protocols

A

 Chemotherapy is given as several doses on a cyclical basis
 It will be given on a specific day with a specific time frame
in between
 The time frame in-between is known as the ‘rest period’ to allow the ‘normal’ cells to recover
 Some protocols may be every 7 days, 14 days, 21 days or 28 days
 Some leukemia protocols may wait until the patient has recovered before commencing the next cycle of treatment
 1st day of chemotherapy in the cycle is considered Day 1
 Allows for better monitoring of side effects to implement interventions e.g. able to estimate time of lowest blood counts (also known as the NADIR) and implementing precautions
 Sequence of treatments in protocol are important to adhere to – DAYS of cycle as well as the ORDER of drugs given on any particular day of the cycle

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22
Q

Response to chemotherapy

A

Complete response - No signs of cancer cells

Partial response - Decrease in number of cancer cells

Stable disease - The cancer has neither grown nor shrunk; no progression

Disease progression - Increase in number of cancer cells

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23
Q

CELL CYCLE SPECIFIC VS NON-SPECIFIC

A

 Although both normal and tumour cells go through growth cycles, the number of cells in the various stages of the cycle may differ in normal and neoplastic tissues

 Cell-cycle specific agents = agents that are only effective against replicating cells in a specific phase of the cell cycle

 Cell-cycle non-specific agents = generally cytotoxic in all phases of the cell cycle but are also effective in tumours with a low percentage of replicating cells

 Chemotherapy agents are divided into classes of agents according to their MOA

24
Q

Chemotherapy drug classes: cell cycle specific

A

Antimetabolites

  • Block the formation and use of nucleic acids essential for DNA replication
  • E.g. methotrexate, fluorouracil, capecitabine, fludarabine

Vinca Alkaloids & Taxanes

  • Interfere with microtubule function required for cell mitosis
  • E.g. Vincristine, paclitaxel, docetaxel

Topoisomerase inhibitors

  • Inhibit the action of topoisomerase I and II and prevent DNA uncoiling
  • E.g. Etoposide, irinotecan
25
Q

Chemotherapy drug classes: non-cell cycle specific

A

Alkylating agents

  • Interfere with DNA base pairing, leading to strand breaks and arresting DNA replication
  • E.g Cyclophosphamide, cisplatin, carmustine

Anti-tumour antibiotics

  • Varying mechanisms of action – may also inhibit topoisomerase
  • E.g. Doxorubicin, epirubicin
26
Q

TARGETED THERAPY When do we choose to use these?

A

Where the tumour expresses a particular target and the targeted therapy has been shown to improve outcomes for that tumour

OFTEN COMBINED WITH CHEMOTHERAPY or radiotherapy to enhance the effectiveness of treatment

As a single agent for maintenance therapy of a potentially curable cancer

Treatment of progressive disease where chemotherapy has been shown to be ineffective

Can be more effective than conventional chemotherapy as they focus on specific molecular and cellular changes

27
Q

Targeted therapy

A

 Targeted therapy interferes with cancer cell growth and division in different ways
 Targeted therapy will usually block or inactivate a particular signaling pathway or receptor that is essential to the tumour growth
 Targeted therapy can act on receptors on the outside of the cell or enter the cell to act on the inside

Common Drug Targets:
• Epidermal Growth Factor Receptor
(EGFR) also known as HER family
E.g. rituximab, trastuzumab
• Tyrosine kinase enzymes
E.g. imatinib, erlotinib
• Vascular Endothelial Growth Factor
(VEGF)
E.g. bevacizumab
28
Q

TARGETED THERAPY – Monoclonal Antibodies

A

 Monoclonal antibodies target extracellular components of the cell cycle pathways, such as ligands and receptor binding domains

 These drugs can be designed to find a particular marker on a cell, attach themselves to the marker and prevent processes that would usually occur when that marker is triggered

 Examples of mABs – rituximab, trastuzumab

29
Q

IV CHEMOTHERAPY – ACCESS DEVICES

A

Cannula
PICC line
Portacath

30
Q

DAY OF TREATMENT: patient assessment

A 
 Temperature
 Blood pressure
 Pulse
 Breathing rate
 Date and Day of Cycle  Current Height
 Current Weight
 Current BSA
 Allergies
 Recent blood test results
 Grading of side effects
 What type of access the patient has
31
Q

PROBLEMS ASSOCIATED WITH CHEMOTHERAPY

A

 Resistance
 Multi-drug resistance
 Treatment-induced tumours
 Toxicity and side-effects

32
Q

Resistance

A

 Defined as a lack of response to drug-induced tumour growth inhibition

 Cells have evolved elaborate defence mechanisms to protect themselves
from chemical toxins, which include chemotherapeutic agents

 Intrinsic resistance: Some neoplastic cells are inherently resistant to most anticancer drugs

 Acquired resistance: Some tumours acquire resistance as a cellular response to drug exposure (mutate)

33
Q

Multi-drug resistance

A

 Cancer multi-drug resistance is defined as the cross- resistance or insensitivity of cancer cells to the cytotoxic actions of various anticancer drugs which are structurally or functionally unrelated and have different molecular targets
 Numerous mechanisms have been proposed to mediate multidrug resistance in cancer cells. These can be categorised as:
• Non-cellular (e.g. limited vascular accessibility)
• Cellular (enzymes and transport systems) e.g. P- Glycoprotein

34
Q

TREATMENT-INDUCED TUMOURS

A

 Treatment-induced tumours (also known as second malignant neoplasms or subsequent neoplasms) are tumours that form after the original cancer was cured (E.g. from 2 months to 10 years or more post treatment)

 These are histologically distinct neoplasms

 Risk is influenced by the type of therapy, environmental exposure, genetic susceptibility and lifestyle choices

 Treatment-induced neoplasms are especially a problem after therapy with alkylating agents or topoisomerase inhibitors

35
Q

TOXICITY AND SIDE-EFFECTS

A

Side effects are often divided into:

 Those occurring during the course of chemotherapy
• Immediate effects (onset hours to days)
• Early-effects (onset days to weeks)
• Late onset (weeks to months)

 Those occurring after therapy has finished
• Delayed/long-term effects (months to years)

36
Q

Side effects experienced from chemotherapy: Immediate and early effects (days, weeks, months)

A

Gastrointestinal

  • Nausea and vomiting
  • Mucositis
  • Diarrhoea

Bone marrow

  • Neutropenia
  • Thrombocytopenia
  • Anaemia

Epidermal

  • Alopecia
  • Nail changes
  • Hand and foot syndrome
  • Extravasation

Neurological
- Peripheral and central neurotoxicity

Organ toxicity

  • Cardiac
  • Pulmonary
  • Liver and renal

Immune

  • Hypersensitivity reactions
  • Increased risk of infection
37
Q

Side effects experienced from chemotherapy: Delayed or longer term effects

A 
Infertility
Secondary cancers
Cognitive changes
Cardiac toxicity
Pulmonary toxicity
38
Q

NAUSEA, VOMITING AND APPETITE CHANGES

A
  • Nausea is very common with chemotherapy, more than vomiting
    • Acute: can occur within 24 hours of chemotherapy
    • Delated: after 24 hours of chemotherapy
    • Anticipatory: occurs prior to the administration or during chemotherapy
- Neurotransmitters mediate the response to nausea and vomiting
• Serotonin (5HT3)
• Substance P (activates NK 1 receptors
• Acetylcholine
• Dopamine
• Histamine
  • Chemotherapy or downstream metabolites may cross the blood brain barrier and trigger
    a release of neurotransmitters signaling nausea and vomiting
  • Some drugs may also irritate the gut causing stimulation of the emetic centre
  • Drug, dose and combination of drugs as well as patient specific factors can also contribute to emesis
39
Q

Emesis potential of chemotherapy

A
  • Centres in the CNS and GI tract control the emetic response to chemotherapy
  • Chemotherapy agents and protocols are classed according to emetogenic potential i.e. the likelihood that the regimen has of causing emesis
40
Q

ANTI-EMETICS USED TO PREVENT AND MANAGE CHEMOTHERAPY-INDUCED NAUSEA

A

NK1 receptor antagonists (aprepitant)

5HT3 antagonists (ondansetron, tropisetron, granisetron, palonosetron)

Corticosteroids (dexamethasone)

Dopamine antagonists (metoclopramide)

Benzodiazepines (lorazepam)

Phenothiazines (promethazine, prochlorperazine)

Others (domperidone, haloperidol)

41
Q

ANTI-EMETICS USED FOR CHEMOTHERAPY-INDUCED NAUSEA

A

High emetogenicity

  • Dexamethasone
  • Aprepitant
  • 5HT3 antagonist

Moderate emetogenicity

  • Dexamethasone
  • 5HT3 antagonist

Low emetogenicity
Dexamethasone and/or metoclopramide

Minimal emetogenicity
No medication or metoclopramide if needed

  • Patients will be given anti-emetics as a pre-medication prior to therapy and also post chemotherapy depending on their treatment protocols and symptoms
  • Close monitoring is essential and anti-emetic regimens are adjusted according to symptoms
  • Side-effects of 5HT3 antagonists include constipation and headache
  • Patient’s should try to maintain their weight, not lose or gain any significant amounts of weight during treatment
42
Q

Bowel changes - chemotherapy

A
  • Chemotherapy-induced diarrhoea is most commonly associated with fluorouracil, capecitabine and irinotecan but can also occur with other agents
  • Chemotherapy induced diarrhoea can quickly become life-threatening if it is not managed appropriately
  • Patients are advised to ensure an adequate fluid intake and may be prescribed loperamide (Gastrostop) for the management of mild-to- moderate diarrhoea
  • Avoiding dehydration is essential
  • Some patients may alternately suffer constipation, likely to be from the use of 5HT3 anti-emetics or to prevent nausea and vomiting, the use of laxatives may assist these patients as well as maintaining a balanced die
43
Q

SIDE EFFECT – MUCOSITIS

A
  • Mucositis is inflammation of the mucous membrane
  • The mouth is lined with rapidly dividing cells which can be affected by chemotherapy leading to mouth sores or ulcers
  • Can be a minor sore mouth, mouth ulcer or complete damage to the mucosal lining
  • Mainly occurs in the mouth but may extend to the throat and stomach
  • Mouth washes that are alcohol-free may be used to assist in treating mouth ulcers
  • Reflux is also a common symptom after chemotherapy requiring treatment with a proton- pump inhibitor (PPI) such as pantoprazole
44
Q

SIDE EFFECT – HAIR LOSS (ALOPECIA)

A
  • Not everyone will lose their hair, it depends on what drugs you are given (E.g. taxanes are more commonly known to cause alopecia)
  • Usually occurs 2-3 weeks after first treatment and in most situations will grow back after chemotherapy has been completed
45
Q

SIDE EFFECT – PERIPHERAL NEUROPATHY

A
  • Peripheral neuropathy is a side effect of some chemotherapy drugs affecting nerve and sensory functions
  • Usually affects the feeling in hands and/or feet
  • Tingling, pins and needles, numbness, loss of motor ability
  • Needs to be reported as soon as possible
46
Q

SIDE EFFECT – BLOOD AND IMMUNE SYSTEM

A
  • Bone marrow is a soft spongey material inside of our long bones which is where our blood cells are made
  • Bone marrow suppression is a common side effect as cells in the bone marrow are rapidly dividing and most likely to be effected by chemotherapy
  • The lowest concentration of blood cells in the peripheral blood after chemotherapy is the NADIR of the blood count i.e. the lowest count of white cells, red cells and platelets
  • The NADIR varies with individual agents and can occur later with the alkylating agents
  • Patients will have their blood counts checked before a cycle of chemotherapy is due
47
Q

REDUCED RED BLOOD CELLS AND PLATELETS

A 
Decreased production of red blood cells(anaemia) can cause:
 Fatigue
 Shortness of breath
 Dizziness
 Concentration problems

Platelets are another part of the blood that help the blood clot…
Reduced production of platelets can cause:
• Bleeding for longer
• Bruising more easily

Some patients require a blood transfusion to help build up their blood cells

48
Q

REDUCED WHITE BLOOD CELLS

A
  • White blood cells can also be affected by chemotherapy
  • White cells fight infection, in particular, neutrophils
  • It is usual to ensure that the neutrophil count is GREATER THAN 1 x 10^9/L before giving the planned dose to ensure there is no risk of FURTHER neutropenia
  • Patient’s neutrophil counts are reviewed regularly from their blood tests, but patients are also advised to regularly check their temperature at home to check it is below 38 degrees.
  • If a patient’s temperature is 38 or above, they are advised to present to the EMERGENCY DEPARTMENT
49
Q

Neutropenia

A
  • When neutrophils fall BELOW 1 x 10^9/L the patient is neutropenic and is at high risk of infection
  • It is an absolute decrease in the number of circulating neutrophil granulocytes
  • Neutropenia is associated with impairment in the inflammatory response, leading to a lack or minimisation of the usual signs and symptoms of infection
50
Q

FEBRILE NEUTROPENIA

A
  • The longer a person is neutropenic, the higher the risk of developing a life- threatening infection!
  • A patient with febrile neutropenia has a temperature >38 degrees Celsius and an abnormally low number of neutrophil granulocytes (febrile = fever)
  • Neutropenia blunts the inflammatory response to infection and also reduces the signs and symptoms of infection – fever may be the only sign!
  • These patients generally require immediate aggressive treatment with broad-spectrum antibiotics and growth colony stimulating factors (GCSF)
51
Q

GROWTH COLONY STIMLULATING FACTORS (GCSF)

A

GCSF are frequently given after a cycle of chemotherapy to enhance neutrophil recovery with the aim of:
• Ensuring the next cycle can be given on time i.e. ensuring the neutrophils have improved by the time chemotherapy is next due
• Preventing infectious complications by minimising the period of neutropenia

GCSF includes filgrastim and pegylated filgrastim (longer-acting)

GCSF is generally given to patients who have a
• Greater risk of developing neutropenic complications or febrile neutropenia based on the tumour and chemotherapy regimen
AND
• Where there is intent to cure to ensure that doses can be delivered at the planned dose and time

52
Q

Preventing infection

A

Check temperature regularly

Eat well cooked food - no buffets

No sick visitors

Avoid heavily crowded areas esp. when counts are lowest 7-10 days post chemo

53
Q

PATIENT CYTOTOXIC PRECAUTIONS

A
  • For around 7 days after chemotherapy, patients may still have traces of chemotherapy in their blood and body fluids
  • Important that they use good hand hygiene
  • Need to close toilet lid before a FULL flush
  • If clothing or bed linen is soiled from vomiting or diarrhoea, they need to be washed separately in a full cycle of HOT water and dried in the sun
  • If they are still still sexually active while on treatment, it is essential a condom is used
  • Otherwise, patient’s on chemotherapy are at no risk to other people so normal contact with other people is OK
54
Q

Immunotherapy

A
  • Immunotherapy, consisting generally of mABs, is a newer class of treatments that enhances the immune system to slow the growth and spread of cancer cells as well as destroy them
  • These drugs attach themselves to biomarkers on the cancer cells and are a more targeted therapy option
  • Different side-effect profile to chemotherapy agents
  • Side-effects are related to the molecular target
    E.g. EGFR is involved in many epidermal processes particular in the skin and GI tract therefore EGFR inhibitors may cause more cutaneous adverse events such as skin rashes, hair changes, nail changes etc.
55
Q

SIDE EFFECTS – mABs

A
  • Flu-like symptoms
    • Fever
    • Chills
    • Sweats
- Skin rashes
 Nausea and vomiting 
 Diarrhoea
 Fatigue
 Headache
 Wheezing 
 Infections
 Weakness 
 Body aches
56
Q

Summary

A

 Different types of cancer require different treatments
 Patients may have different treatment goals and protocols
 Patients may be on a combination of treatment options
 The administration and handling of chemotherapy requires cytotoxic precautions
 There are numerous side-effects associated with chemotherapy
 Side-effects can also occur from targeted therapies and these may differ from chemotherapy
 Supportive therapy medications are used to assist with the management of SEs

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