Cancer Chemotherapy I Flashcards
Classically, what have chemotherapeutic agents inhibited?
DNA/RNA/protein synthesis and protein activity
What are the characteristics of the ideal anti-neoplastic drug?
- non-toxic to normal cells
- kills all tumor cells
- broad spectrum of activity
- good distribution in body, adequate half life
- non-immunogenic/low incidence of side effects
- low cost, oral dosing
**ALL drugs fall far short of this ideal
What are some common problems with the currently available anti-neoplastics?
- many have poor selective toxicity
- most drugs affect only actively growing cells
- many drugs have limited anti-tumor spectrum
- high incidence of side effects
- some cause secondary malignancies (2nd tumor with new pathology develops years after initial chemo)
What are the characteristics of a “cell killing compound”?
**cause widespread (nonspecific) cell death
- direct killing (necrosis)
- trigger apoptosis (problem= potentially reversible)
What are the characteristics of a “cytostatic compound”?
**stop cell growth
- induce terminal differentiation
- interfere with growth signals
Where do antimetabolites halt the cell cycle? Examples?
**S phase
- Cytarabine, Fluorouracil= pyrimidine analogs
- Methotrexate= folic acid analog
- Mercaptopurine= purine analog
- Hydroxyurea= substituted urea
Where does prednisone halt the cell cycle?
G1 phase (corticosteroid)
What drugs halt the cell cycle in G2 phase?
- Bleomycin, Etoposide (antibiotics)
- Paclitaxel (taxane/taxol)
Where do vinca alkaloids halt the cell cycle? Examples?
**M phase
- Vinblastine, Vincristine= mitotic inhibitors
What are the three “compartments of a tumor”?
- Dividing cells (very sensitive to drugs when used optimally)
- Temporarily non-dividing cells in Go (partially/completely insensitive to drugs depending on class)
- Permanently non-dividing cells (of little concern, except for physical presence)
Why does the presence of cancer stem cells matter in therapy?
The presence of cancer stem cells is one mechanism for drug resistance, and they can regenerate tumors
What characteristic makes a tumor cell more sensitive to chemotherapy?
Human neoplasms that are currently the most susceptible to anti-neoplastic drugs have a high percentage of actively dividng cells (e.g. leukemia, lymphoma)
What is the “log kill” relationship?
- 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
What is the effect of shorter treatment interval?
Although you get better killing of the tumor cells, patient’s own cells also experience more killing (no time for regeneration)
Compare tumor killing vs patient survival
One surviving cell can regenerate the tumor
Life span of the patient is inversely related to the number of cells that survive therapeutic measures
**curative chemo regimen must have 2-4 log-kill efficiency and be repeated for 4-12 cycles
Describe how Class II drugs treat cancer
- Class II= cell cycle-specific/phase-specific drugs
- given either by continuous infusion or in frequent small doses
- Halt cells in G1, S, G2, or M (know specific examples)
How does a chemo drug’s class affect dose survival of cells?
- Class I has the possibility to kill all cells
- Class II can kill all cells except those in Go
- Class III can kill only cells in the phase the drug is specific for
Describe how chemotherapy timing can affect outcome
- there is a “sweet spot” of time between doses that will kill the tumor cells but allow regeneration of normal cells -> potential cure
- __As a general rule, normal cells have a faster doubling time and are better at recovering
- toxic death is possible if treatments are too close together
- progressive disease is possible if treatments are too far apart
