Cancer Chemotherapy Flashcards
the medical treatment of cancer is based upon clear understanding of what 3 things?
- the drug action
- potential for harmful side effects
- mechanisms of drug resistance
- principles of combination therapy
what does it mean to say that cancer treatment is multimodal
sugery, radiation, chemotherapy
What is the rationale for anti-neoplastic drugs
- kill all tumor cells but not normal cells
- supress the growth of tumor but not normal cells
- increase the host capcity to fight cancer
what are 7 things that the ideal anti-neoplastic drug should have?
- non-toxic to normal cells
- kill 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
unfortunately all drugs fall short…
What are currently availabel anti-eoplastic liks
- poor selective toxicity
- selectivity is largely based on differences in cell kinetics between normal and tumor cells
- most drugs affect only actively growing cells
- many drugs have limited anti-tumor spectrum
- high incidence of side effects
- some cause secondary malignancies
what drugs are associated with high risk of secondary malignancy
mechlorethamine
carmustine
etoposide
what drugs are associated with moderate risk of secondary malignancies
doxorubicin
cyclophosphamide
procarbazine
cisplatin
what drugs are associated with low risk of seconadry malignancies
vincristine, vinblastine
methotrexate
cytarabine
5-fluorouracil
what drugs are associated with unknon risk of secondary malignancies
bleomycin
paclitaxel
What ar 2 general ways to stop tumor growth
- cause cell death-cell killing compounds
- direct killing (necrosis)
- trigger apoptosis
- many anti-neoplastice do this
- potential problems! ie can be reveersibel/resistance
- stop growth-Cytostatic compounds
- induce terminal differentiation (can’t return to proliferative state)
- interfere with growth sginals
What is the foundation for combination therapy
cells are either
- dividing: M, G1, S, G2
- temporarily non dividing: G0
- permanently nondividing: terminally differentiated
What are 2 current cancer research interests
- cancer stem cells
- drug resistance
describe the current research in cancer stem cells
- small compartment of tumor
- often quiescent (go)
- resistant to chemotherapy and radiation
- mulitple mechniasms
- can regulate tumors
- an important reasson for therapeutic failure/recurrence
describe the drug resistance research
- intrinsic (genetic) and inducible (environmental)
- the same drug/the same class or cross-resistance
- multiple mechanisms
- may ocur individually
- an important reason for therapeutic failure/recurrence
tumor growth rate decreases with ________
time!
actively growing tumor cells are generally more sensitive to chemotherapeutic agents
human neoplasms that are currently the most susceptible to anti-neoplastic drugs have ________-
a high percentage of actively dividing cells (leukemia, lymphoma)
Killing of tumors follows _______ kinetics
killing of tumors follows first-order kinetics
describe how killing of tumors follows first-order kinetics
- a constant dose of drugs kills a constant fraction (not number) of tumor cells
- tumor size does not predict dose, but it does predict duration of therpay
- log kill best applies to early stages of tumor growth
what does it take to regenerate a tumor
one surviving cell can regenerate the tumor
the life span of the patient is inversely related to
the number of cells that survive therapeutic measures
- to be surative, a chemotherapy regimen must have a 2-4 log kill efficiency and be repeated for 4-12 cycles of therapy
- in general, a 2-4 log-kill is needed to at least doube the expected lifespans of the patient
what is the example of 2-log kill progression
with each round you kill 90% of tumor cells
so first round: .9, then next round .99, then .999, then .9999
What is class I: cell-cycle nonspecific drugs
- exert cytotoxicity in a nonspecific manner
- kill cells in any stage of cell cycle even Go
- kill normal and neoplastic cells to the same extent
- ex: alkylating agents: Mechlorethamine, Carmustine
What 2 agents are in the Alkylating agents class?
Mechlorethamine, Carmustine
What are Class II drugs?
Cell-Cycle specific/phase specific drugs
- tagrte specific phase of the cell cycle
- given either by continous infusion or in frequent small doses
