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FPP Block 1 > Cancer Chemotherapy > Flashcards

Cancer Chemotherapy Flashcards

1
Q

the medical treatment of cancer is based upon clear understanding of what 3 things?

A
  1. the drug action
  2. potential for harmful side effects
  3. mechanisms of drug resistance
  4. principles of combination therapy
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2
Q

what does it mean to say that cancer treatment is multimodal

A

sugery, radiation, chemotherapy

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3
Q

What is the rationale for anti-neoplastic drugs

A
  1. kill all tumor cells but not normal cells
  2. supress the growth of tumor but not normal cells
  3. increase the host capcity to fight cancer
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4
Q

what are 7 things that the ideal anti-neoplastic drug should have?

A
  1. non-toxic to normal cells
  2. kill all tumor cells
  3. broad spectrum of activity
  4. good distribution in body, adequate half-life
  5. non-immunogenic
  6. low incidence of side effects
  7. low cost, oral dosing

unfortunately all drugs fall short…

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5
Q

What are currently availabel anti-eoplastic liks

A
  • 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
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6
Q

what drugs are associated with high risk of secondary malignancy

A

mechlorethamine

carmustine

etoposide

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7
Q

what drugs are associated with moderate risk of secondary malignancies

A

doxorubicin

cyclophosphamide

procarbazine

cisplatin

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8
Q

what drugs are associated with low risk of seconadry malignancies

A

vincristine, vinblastine

methotrexate

cytarabine

5-fluorouracil

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9
Q

what drugs are associated with unknon risk of secondary malignancies

A

bleomycin

paclitaxel

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10
Q

What ar 2 general ways to stop tumor growth

A
  1. cause cell death-cell killing compounds
    1. direct killing (necrosis)
    2. trigger apoptosis
      1. many anti-neoplastice do this
      2. potential problems! ie can be reveersibel/resistance
  2. stop growth-Cytostatic compounds
    1. ​induce terminal differentiation (can’t return to proliferative state)
    2. interfere with growth sginals
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11
Q

What is the foundation for combination therapy

A

cells are either

  1. dividing: M, G1, S, G2
  2. temporarily non dividing: G0
  3. permanently nondividing: terminally differentiated
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12
Q

What are 2 current cancer research interests

A
  • cancer stem cells
  • drug resistance
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13
Q

describe the current research in cancer stem cells

A
  • small compartment of tumor
  • often quiescent (go)
  • resistant to chemotherapy and radiation
    • mulitple mechniasms
  • can regulate tumors
  • an important reasson for therapeutic failure/recurrence
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14
Q

describe the drug resistance research

A
  • 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
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15
Q

tumor growth rate decreases with ________

A

time!

actively growing tumor cells are generally more sensitive to chemotherapeutic agents

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16
Q

human neoplasms that are currently the most susceptible to anti-neoplastic drugs have ________-

A

a high percentage of actively dividing cells (leukemia, lymphoma)

17
Q

Killing of tumors follows _______ kinetics

A

killing of tumors follows first-order kinetics

18
Q

describe how killing of tumors follows first-order kinetics

A
  • 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
19
Q

what does it take to regenerate a tumor

A

one surviving cell can regenerate the tumor

20
Q

the life span of the patient is inversely related to

A

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
21
Q

what is the example of 2-log kill progression

A

with each round you kill 90% of tumor cells

so first round: .9, then next round .99, then .999, then .9999

22
Q

What is class I: cell-cycle nonspecific drugs

A
  • 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
23
Q

What 2 agents are in the Alkylating agents class?

A

Mechlorethamine, Carmustine

24
Q

What are Class II drugs?

A

Cell-Cycle specific/phase specific drugs

  • tagrte specific phase of the cell cycle
  • given either by continous infusion or in frequent small doses
25
Q

what agent is most specific for G1

A

prednisone

26
Q

what agent is most specific for S phase

A

Cytarabine, fluorouracil, methotrexate, mercaptopurine, hydroxyurea

27
Q

what agents are most specific for G2 phase

A

bleomycin, etoposide, paclitaxel

28
Q

what agents are most specific for M phase

A

vinblastine, vincristine

29
Q

WHat are Class III drugs and list some examples

A

cell cycle specific/phase nonspecific drugs

  • target cells in cell-cycle without regard for specific phase of cell cycle (all dividing cells but Go)
    • administered in single large doses to take advantage of their sparing effect on those normal cells that may be in Go
  • cyclophosphamide, cisplatin, doxorubicin
30
Q

what has the best log kill effect

A

alkylating agents

31
Q

Please describing chemotherapy timing vs outcome

A

potential cure: kill tumor, not normal cells

Toxic death: kill tumor but also patient

Progressive death: too much delay, don’t kill tumor or normal ineffective

32
Q

Differential cell kill depends on _______

A

recovery of normal vs tumor cells

33
Q

common anti-neoplastics frequently have sever toxicities and side effects

A
  1. Hematopoietic toxicity
  2. gastrointestinal toxicity
  3. organ-specific toxicity
34
Q

what is the goal of cancer treatment?

A

slectively inhibit cancer, but not normal, cell growth

FPP Block 1 (18 decks)

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