Chemotherapy Flashcards
What does chemotherapy involve?
The use of pharmacological agents to kill tumour cells
What can chemotherapy be effective in treating?
Both primary tumours and metastatic spread
How does chemotherapy work?
It acts at different stages of the cell cycle, and exerts its effects primary by 3 different mechanisms;
- Altering the chemistry of nucleic acids
- Interfering with DNA or RNA synthesis
- Disrupting mechanisms of cell devision
Are chemotherapy agents selective?
Most of the common agents act in a non-selective manner
What is meant by most chemotherapy agents acting in a non-selective manner?
They not only damage cancer cells, but affect normal dividing cells
What normal dividing cells are particularly affected by chemotherapy?
- Hair follicles
- Bone marrow
- Gastrointestinal mucosa
What is the result of chemotherapy agents acting in a non-selective manner?
It produces side effects that limit the dose that can be administered and the recovery time before the next dose can be given
How is most chemotherapy given?
As a combination of drugs administered IV on an intermittent basis
On average, how often is an individual cycle of chemotherapy repeated?
Every 21-28 days
How many cycles does a typical course of chemotherapy consist of?
6
What is the purpose of intermittent dosing in chemotherapy?
Malignant cells have less capacity for repair than normal cells, and intermittent dosing exploits the fact that tumour cells recover from cytotoxic damage more slowly than normal cell populations
What does each sequential treatment cycle of chemotherapy allow?
Normal stems cells time to recover
What is the chemotherapy drug dose usually calculated from?
Surface area of patient, based on height and weight
What is pharmacodynamics?
The study of the effect that drugs have in the body
Why is pharmacodynamics significant in chemotherapy?
In terms of dose-limiting toxicity, which can be used to determine the maximum possible dose in an individual patient
What is pharmacokinetics?
The study of the effects that the body has on the drug
What can pharmacokinetics be modified by?
- Renal and hepatic function
- Drugs clearance from the circulation
What is the result of the potential for modification of pharmacokinetics with chemotherapy?
Careful monitoring of the patient’s biochemistry, renal, liver, and bone marrow function is essential during chemotherapy treatment
What is the downside of chemotherapy?
It is highly toxic with the potential for life-threatening side effects
How is the potential for life threatening side effects of chemotherapy reduced?
- Requires supervision from specialists
- Patients should have careful assessment prior to commencement of treatment, and prior to each cycle
What is a reliable predictor to tolerance of chemotherapy treatment?
Patient fitness
What is the result of poor fitness when having chemotherapy?
- Will not tolerate chemotherapy as well
- Increased risk of adverse effects
How is the effects of poor fitness in chemotherapy patients combatted?
It is important to assess the patient’s performance status to determine patient suitability for chemotherapy and appropriate dosing of treatments
What is growth fraction?
The percentage of cells in a tumour mass that are actively dividing
Give an example of a cancer with a high growth fraction
Burkett’s lymphoma
What is the growth fraction in Burkett’s lymphoma?
50% (doubling time of 24 hours)
Give an example of a cancer with a low growth fraction?
Some adenocarcinomas
What is the growth fraction in some adenocarcinomas?
Immeasurable (doubling time of up to 200 days)
What can chemotherapy agents be divided into?
- Cell cycle independent
- Cell cycle dependent
What can chemotherapy agents that are cell cycle dependent be further subdivided into?
- Phase non-specific
- Phase specific
What is meant by a chemotherapy agent being phase non-specific?
They are equally active against cells in all phases of the cell cycle except G0
What is meant by a chemotherapy agent being phase specific?
It is only active against cells in one phase of the cycle
How can if a chemotherapy is phase specific or phase non-specific be utilised clinically?
These features can be used to design drug regimen combinations and schedules that take advantage of individual drug characteristics
Where kind of cells does the normal process of tissue renewal involve?
Both actively proliferating and quiescent stem cells
What is true of the quiescent stem cells that are involved in normal tissue renewal?
They are in the G0 phase of the cell cycle
Why is it significant that quiescent stem cells involved in normal tissue renewal are in the G0 phase of the cell cycle?
Because most anti-cancer agents are not active against these cells
What is a single clonogenic malignant cell capable of?
Multiplying and ultimately killing the host
What does the fact that a single clonogenic malignant cell is capable of multiplying and ultimately killing the host imply?
That cure depends on total cell eradication of all malignant cells