17 - Cancer Chemotherapy 1 Flashcards
(38 cards)
The medical treatment of cancer patients is based on a clear understanding of what four things?
- The drug action
- Potential for harmful side effects
- Mechanisms of drug resistance
- Principles of combination therapy
What types of cancer are most curable? What is often the best treatment?
Early stage cancers are more curable than late-stage cancers.
The beast treatment is often found through participation in clinical trials.
What are common practices for cancer chemotherapy?
Multi-modal: surgery, radiation, chemotherapy
Rationale for nati-neoplastic drugs:
- Kill all tumor cells but not normal cells
- Suppress growth of tumor but not normal cells
- Increse host capcity to fight cancer
What are characteristics of an ideal anti-neoplastic drug?
- Non-toxic to normal cells but kills all tumor cells with broad spectrum activity
- Good distribution in the body with adequate half-life
- Non-immunogenic
- Low incidence of side effects
- Low cost, oral dosing
All drugs fall short of this idea
What is the downsides to currently available anti-neoplastics? What do these target?
Poor selectivity (which is normally based on differences in tumor and normal cell kinetics)
Most drugs affect only actively growing cells
Many have limited anti-tumor spectrum
High incidence of side effects
Some cause secondary malignancies
Normal systems can withstand greater ______ _____ than tumors.
cell losses
What anti-neoplastic drugs are associated with a high risk of causing secondary malignancies in humans?
- Mechlorethamine
- Carmustine
- Etoposide
What anti-neoplastic drugs are associated with a moderate risk of causing secondary malignancies in humans?
- Doxorubicin
- Cyclophosphamide
- Procarbazine
- Cisplatin
What anti-neoplastic drugs are associated with a low risk of causing secondary malignancies in humans?
- Vincristine, vinblastine
- Methotrexate
- Cytarabine
- 5-fluorouracil
What anti-neoplastic drugs are associated with an unknown risk of causing secondary malignancies in humans?
- Bleomycin
- Paclitaxel
What are the two general ways to stop tumor growth/kill cancer cells?
1. Cause cell death via cell killing compounds
- direct killing (necrosis)
- Trigger apoptosis (many anti-neoplastics do this)
2. Stop growth - cytostatic compounds
- induce terminal differentiation of tumor cells
- Interfere with growth signals
How long is the human cell cycle normally? What about in cells of the BM and GI lining?
Human cell cycle: 16-260 hours
BM and GI lining: 24-48 hours due to rapid proliferation (these are the tissues most sensitive to chemo - which is why we see toxicity here)
What are the three cellular compartments of a tumor? Which are more sensitive to drugs?
- Dividing cells (cells in M, G1, S, and G2): very sensitive to drugs
- Temporarilty non-dividing cells (cells in G0): partially to completely insensitive to drugs, depending on class. Of partial concern ebcause they may re-enter the cell cycle and divide again.
- Permanently non-dividing cells(terminally differentiated): of little concern except for physical presence.
What is an important mechanism for cancer drug resistance?
Cancer stem cells: small, often quiescent (G0) part of the tumor that’s resistant to chemo and radiation and can regenerate more tumor.
When is the tumor most susceptible to chemo? What is the issue with this?
Actively growing tumors are generally more sensitive to chemotherapeutic agents.
The problem with this is that the patient is usually asymptomatic during the log effect proliferation of the tumor and by the time they have symptoms the actively growing phase will be over.
At what size is a tumor visible on X-ray? At what size is it palpable? What about symptomatic?
Visible on Xray: 1 cm diameter
Palpable: 1 g
Symptomatic: 1 g
What cancers are most susceptible to anti-neoplastic drugs? What are exampels?
Neoplasms that have a high percentage of actively dividing cells (ie leukemia and lymphoma)
Describe log kill? What type of kinetics does killing of tumors follow?
First round: percentage of tumor cells killed is 90% and percentaeg of surviving cells is 10% > this is a log kill of 1.
Next round: you kill 90% of what’s left, making the tumor cells kill percentage up to 99% and the surviving cell percentage at 1% > this ia a log kill of 2.
Killing of tumors follows first-order kinetics
Describe how the killing of tumors follows first order kinetics?
A constant dose of drug kills a constant fraction (not number) of tumor cells.
Tumor size does not predict dose, but it does predict duration of therapy.
Log kill best applies to early stages of tumor growth.
Why do you need a waiting period between doses of chemotherapy?
Because normal cells need time to recover.
What is the effect of a shorter treatment interval?
Increasing the frequeny and dosing interval can increase the therapeutic effect.
Describe the benefits of a sequential/interval effect dosing on a heterogeneic tumor?
You can design a protocol in which you give a drug that targets the fast proliferating cells first, and then give a drug that targets the slow proliferating cells of the tumor second.
Increading the frequency of these drugs improves their effect.
______ cell(s) can regenerate the tumor? What is the lifespan of a patient inversely related to?
One surviving cell can regenerate a tumor.
The lifespan of a patient is inversely related to the number of cells that survive terapeutic measures.
Clinically, you want to achieve _____ log kill when treating a tumor.
2-4 log kill
