THE PRINCIPLE OF CYTOTOXIC AGENTS IN GYNAECOLOGY Flashcards
T/F: Use of cytotoxic should be restricted to patient in which diagnosis of cancer has been confirmed by either biopsy or cytology
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T/F: In the use of cytotoxic drugs it is important to ascertain whether a patient has measurable disease and / or elevated tumour marker.
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10 hallmarks of cancer
- Evading growth suppressors
- Avoiding immune destruction
- Enabling replicative immortality
- Tumor-promoting inflammation
- Activating, invasion and metastasis
- Inducing angiogenesis
- Genome instability and mutation
- Resisting cell death
- Deregulating cellular energetics
- Sustaining proliferative signalling
6 objectives of cytotoxic chemotherapy
- To achieve complete cure
- To achieve best possible survival
- To relieve agony by palliation in terminal cases
- To prevent reoccurrence
- To reasonably reduce distant and regional metastasis and if present, to treat them
- To improve the result of surgery, radiotherapy and immunotherapy
4 chemotherapeutic responses of tumours
- Highly chemo-sensitive
- Chemosensitive
- Low sensitivity
- Chemo-resistant
T/F: Cure is achieved in highly chemosensitive tumors
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2 examples of highly chemosensitive tumors
- Ovarian germ cell tumors
- Gestational trophoblastic tumor
T/F: Cure is uncommon in chemosensitive tumors
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Chemotherapy improves survival but does not restore a normal life expectancy
Example of a chemosensitive tumor
Epithelial cancer of the ovary with 70-80% response but most patient will have relapse
% response of epithelial cancer of the ovary to cytotoxic chemotherapy
70 - 80%
Example of tumors with low sensitivity to chemotherapy
Uterine leiomyosarcoma
T/F: In tumors with low sensitivity to chemotherapy impact of therapy over survival rate is not clear
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Example of chemoresistant tumor
Metastatic melanoma
Response of chemoresistant tumors to cytotoxic chemotherapy
Low or unpredictable response
Therapeutic index is —
Quantitative measurement of drug safety
The ratio of the dose that produces toxicity to the dose that produces a clinically desired or effective response
The ratio of the dose that produces toxicity to the dose that produces a clinically desired or effective response
Therapeutic index
T/F: A safer drug has a higher therapeutic index
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3 biological concepts influencing treatment
Cell cycle
Cell kinetics concepts
Cancer cell growth
Duration of cycle from M phase to another M phase.
Generation time
Maximum variation seen with generation time is in which phase of cell cycle
G0
T/F: Dividing cells that are actively traversing the cell cycle are most sensitive to chemotherapy
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The time required to complete the five phases of the cell cycle
The cell generation time
Fate of G1 cells
G1 cells may either terminally differentiate into the G0 phase or reenter the cell cycle after a period of quiescence
3 activities seen in G1
protein synthesis, RNA synthesis, and DNA repair.
T/F: Cells with prolonged G1 are considered to be in the G0 phase
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G0 = resting phase
What happens in S phase
New DNA is synthesized
T/F: The G2 (premitotic) phase is characterized by cells having twice the DNA content as they prepare for division
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T/F: Actual mitosis and chromosomal division take place during the M phase
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T/F: Tumors have faster generation times
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Tumors do not typically have faster generation times. They instead have many more cells in the active phases of replication and have dysfunctional apoptosis (programmed cell death)
T/F: Normal tissues have a much larger number of cells in the G0 phase
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T/F: Normal tissues have a much larger number of cells in the G0 phase
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The human body contains — number of cells
5 x 10^13 cells
At what size do tumor cells become clinically detectable
Tumour becomes clinically detectable when there is a mass of 10^9 cells (1 g)
T/F: Cell cycle specific agents are most active in the S phase of the cell cycle
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T/F: Cell cycle specific agents are most active in the S phase of the cell cycle
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What is Gompertzian growth?
This means exponential spurt and exponential growth retardation over entire duration of tumour growth i.e. as the tumour size increases rapidly then the time required in the doubling its size also increases
T/F: When a cancer is microscopic and nonpalpable, growth is exponential
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T/F: Chemo therapeutic drugs work by 1st order kinetics
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What is 1st order kinetics
Killing of a constant fraction of cells rather than a constant number
T/F: The cure rate of chemotherapeutic drugs will be significantly increased if the tumour mass is small
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6 mechanisms of chemotherapy drug resistance
- Increased rate of drug deactivation
- Decreased killing activity of drug
- Increased drug efflux
- Decreased drug intake by tumour cells
- Altered efficacy of inhibiting enzymes
- Increased production of drug target enzymes
What is the GOLDIE COLDMAN HYPOTHESIS
The probability that a given tumor harbors drug-resistant cells at the time of diagnosis is a function of the size of the tumor and the frequency of the mutation
