Principles of Cancer Chemotherapy Flashcards
(38 cards)
What is “selective toxicity” with respect to neoplasis and explain what normal cells are most susceptible to certain anti-neoplastics
- selective toxicity can be described in terms of chemotherapeutic index (CTI)
- CTI = (toxicity to cancer cells, i.e. lethal dose)/(toxicity to normal cells)
- fastgrowing/developing cells are most susceptible, i.e. blood cells, follicle cells, GI cells, sperm
What are 3 advantages of using combinations of anti-cancer drugs?
- It provides maximum cell kill within the range of toxicity tolerated by the host for each drug.
- It offers a broader range of coverage of resistant cell lines in a heterogeneous tumor proliferation.
- It prevents or slows the development of new-drug resistant cell lines.
Compare primary vs. acquired drug resistance.
- primary resistance: absence of response on the FIRST EXPOSRUE to currently available standard agents
- acquired resistance: develops after exposure and is not innate
How does p-glycoprotein function as an energy-dependent efflux pump for anti-tumor agents?
P-glycoprotein is expressed on tumor cells and is associated with multidrug resistance. It is expressed via the MDR1 gene. It uses ATP to expel a variety of foreign molecules. It has 2 binding sites for ATP, but only one binding site is involved in drug transport.
What are 3 types of cells that are possibly reduced during myelosuppression and what would be the Sx associated with each?
- Low WBC count (leukopenia): infection, fever, sore throat, cough or shortness of breath, ansal congestion, urination burning, shaking chills, redness, swelling and warmth at injury site.
- Low RBC counts (anemia): fatigue, dizziness, headache, irritability, shortness of breath, increase in HR/breathing
- Low platelet counts: bruise easily, bleed longer after cuts, bleeding gums, nose bleeds, echymyoses (large bruise), petechiae (small bruise), internal bleeding
What are 3 serotonin antagonists given as anti-nausea agents in cancer pts?
- Dolasetron
- Granisetron
- Ondansetron
* these are the most effective drugs for the management of nausea and vomiting associated with radiotherapy or chemotherapy as well as many disease processes
Describe the relationship between the CTZ and vomiting center and give 2 receptors in the vomiting center.
The chemoreceptor trigger zone (CTZ) sends signals to the vomiting center (VC) upon stimulation.
2 receptors in the VC are serotonin and dopamine receptor (in CTZ mostly, not VC)
What are 3 antidopaminergics given as anti-nausea agents in cancer pts and how do they work?
- Prochlorperazine
- Fluphenazine
- Chlorpromazine
* they work by selectively depressing the CTZ and the vomiting center to a lesser extent
* these are second line drugs useful in treating mild to moderate nausea and vomiting
What is chemotherapeutic index (CTI) and how is toxicity measured?
CTI = toxicity to cancer cells (lethal dose)/toxicity to normal cells
*toxicity is measured by LD50 (lethal dose for 50% cell population)
What normal cells are susceptible?
cells that divide quickly - GI cells, blood cells, platelets, sperm cells
What defines the best chance for chemotherapy to have a cure?
administration of the drug that can acheive a fractional cell kill in a log fashion, i.e. 1-log kill is 90% of the cells, 2-log kill is 99% of cells)
Describe the importance of rapid and frequent chemotherapy Tx in a fast-growing neoplasia.
If Tx is given rapidly and freqnetly, via combination Tx, tumor cell kill exceeds regrowth which can be a possible cure.
If Tx is given infrequently, there is prolongation of survival, but recurrence of Sx.
Surgery combined with combo therapy has rapid decline of cancer cells.
A 40 yo man with no significant med Hx presents to physician with complaints of ab pain, N&V, and weight loss. Physical exam reveals only mild anemia (Hb 11gm/dL; hematocrit is 33%). A CT scan of the abdominal region revealed a mass present in the peri-pancreatci that is suggestive of malignancy. What should you not tell the man at this point. What Tx are available?
Should not tell him it is cancer if you are not certain, but don’t tell the pt to go home yet. Take a biopsy, pain management, surgery, cancer therapy as appropriate.
What are 3 benefits of combination therapy?
- maximum cell kill tolerated by host
- broader range of coverage
- prevents/slows development of new resistant lines
What is the difference between primary and acquired resistance?
Cells ath don’t respond to the first type of Tx exhibit primary resistance. Acquired resistance develops in a number of drug-sensitive tumor types.
Describe the relationship between efflux pumps and multidrug resistance,
P-glycoprotein (from MDR1 gene) is a cell surface drug efflux pump that can take out a number of anti-cancer and antibiotic drugs. It is present on many cancerous cells and allows the cell to be resistant to each specific drug. P glycoprpotein efflux pump pushes drug out which reduces effectiveness of drug.
What are 3 Ca2+ channel blockers that can reverse multidrug resistance?
- Verapamil
- Quinidine
- Cyclosporin
A 23 yo man is Dx with Stage II favorable Hodgkin’s disease. He is begin on the ABVD Tx combo to be given in combo with irradiation. He is very reluctant because of his fear of side effects. He asks if he can receive 1 drug at a time rather than all 4 drugs at once. Is this a good idea?
No - it can lead to cancer cell resistance and cells would continue to grow if only 1 drug was given at a time. All 4 drugs must be taken at once.
After Tx, Hodgkin’s pt undergoes assessment of cancer load of 2 cycles using PET-CT of mediastinum lymph nodes. It reveals a slight increase in neoplastic cell load. Why might this Tx be failing?
Perhaps the drug is not being given rapidly and frequently enough to kill enough tumor cells.
Hodgkins pt is continued on ABVD with more frequent Txs. After 2 more cycles, there is a 20% reduction in lymph node size upon PET-CT, which is disappointing. Which agent may be failing and why?
Neoplasma has developed drug resistance to vinblastine via MDR-1 gene and P-glycoprotein efflux
What are 3 goals of chemotherapy?
- control the spread of tumor cells (maybe shrink it before surgery)
- possibly cure the disease
- palliative care
Where are the 2 locations where antiemetic drugs act?
both locations are in the vomiting center of the medulla:
- chemoreceptor trigger zone (CTZ)
- vestibular apparatus (VA)
* drug therapy is more successful for prophylaxis than for Tx for nausea and vomiting
What are 3 serotonin-receptor antagonists and what is special about them?
- Dolasetron (ANZEMET)
- Granisetron (KYTRIL)
- Ondasetron (ZOFRAN)
* these are 1st line antiemetic therapy - most effective drugs for the managemetn of N&V associated with radiotherapy or chemotherapy
How many DA and 5HT receptors each are in the vomiting center?
2 DA receptors and 3 serotonin receptors
