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Found. of Path. Processes - Block 1 > 17 - Cancer Chemotherapy 1 > Flashcards

17 - Cancer Chemotherapy 1 Flashcards

1
Q

The medical treatment of cancer patients is based on a clear understanding of what four 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 types of cancer are most curable? What is often the best treatment?

A

Early stage cancers are more curable than late-stage cancers.

The beast treatment is often found through participation in clinical trials.

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3
Q

What are common practices for cancer chemotherapy?

A

Multi-modal: surgery, radiation, chemotherapy

Rationale for nati-neoplastic drugs:

  1. Kill all tumor cells but not normal cells
  2. Suppress growth of tumor but not normal cells
  3. Increse host capcity to fight cancer
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4
Q

What are characteristics of an ideal anti-neoplastic drug?

A
  • 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

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5
Q

What is the downsides to currently available anti-neoplastics? What do these target?

A

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

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6
Q

Normal systems can withstand greater ______ _____ than tumors.

A

cell losses

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7
Q

What anti-neoplastic drugs are associated with a high risk of causing secondary malignancies in humans?

A
  • Mechlorethamine
  • Carmustine
  • Etoposide
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8
Q

What anti-neoplastic drugs are associated with a moderate risk of causing secondary malignancies in humans?

A
  • Doxorubicin
  • Cyclophosphamide
  • Procarbazine
  • Cisplatin
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9
Q

What anti-neoplastic drugs are associated with a low risk of causing secondary malignancies in humans?

A
  • Vincristine, vinblastine
  • Methotrexate
  • Cytarabine
  • 5-fluorouracil
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10
Q

What anti-neoplastic drugs are associated with an unknown risk of causing secondary malignancies in humans?

A
  • Bleomycin
  • Paclitaxel
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11
Q

What are the two general ways to stop tumor growth/kill cancer cells?

A

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
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12
Q

How long is the human cell cycle normally? What about in cells of the BM and GI lining?

A

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)

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13
Q

What are the three cellular compartments of a tumor? Which are more sensitive to drugs?

A
  1. Dividing cells (cells in M, G1, S, and G2): very sensitive to drugs
  2. 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.
  3. Permanently non-dividing cells(terminally differentiated): of little concern except for physical presence.
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14
Q

What is an important mechanism for cancer drug resistance?

A

Cancer stem cells: small, often quiescent (G0) part of the tumor that’s resistant to chemo and radiation and can regenerate more tumor.

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15
Q

When is the tumor most susceptible to chemo? What is the issue with this?

A

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.

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16
Q

At what size is a tumor visible on X-ray? At what size is it palpable? What about symptomatic?

A

Visible on Xray: 1 cm diameter

Palpable: 1 g

Symptomatic: 1 g

17
Q

What cancers are most susceptible to anti-neoplastic drugs? What are exampels?

A

Neoplasms that have a high percentage of actively dividing cells (ie leukemia and lymphoma)

18
Q

Describe log kill? What type of kinetics does killing of tumors follow?

A

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

19
Q

Describe how the killing of tumors follows first order kinetics?

A

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.

20
Q

Why do you need a waiting period between doses of chemotherapy?

A

Because normal cells need time to recover.

21
Q

What is the effect of a shorter treatment interval?

A

Increasing the frequeny and dosing interval can increase the therapeutic effect.

22
Q

Describe the benefits of a sequential/interval effect dosing on a heterogeneic tumor?

A

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.

23
Q

______ cell(s) can regenerate the tumor? What is the lifespan of a patient inversely related to?

A

One surviving cell can regenerate a tumor.

The lifespan of a patient is inversely related to the number of cells that survive terapeutic measures.

24
Q

Clinically, you want to achieve _____ log kill when treating a tumor.

A

2-4 log kill

25
Q

Chemotherapy can be divided into three classes, what is the first class of anti-neoplastic agents How do they work?

A

Class 1: Cell cycle - nonspecific drugs

Exert cytotoxicity nonspecifically and kill cells in any stage of the cell cycle, even G0.

Kills normal and neoplastic cells to the same extent.

26
Q

What is an example of a class 1 anti-neoplastic agent? Give examples.

A

Alkylating agents:

  • mechlorethamin
  • carmustine
27
Q

What is the second class of anti-neoplastic agents? How do they work?

A

Class II: Cell cycle-specific / phase specific drugs

Target specific phases of the cell cycle

Given by continuous infusion or in frequent small doses.

28
Q

What class II anti-neoplastic drug kills cells in the G1 phase of the cell cycle?

A

Prednisone

29
Q

What class II anti-neoplastic drugs kills cells in the S phase of the cell cycle?

A

Cytarabine

Fluorouracil

Methotrexate

Mercaptopurine

Hydroxyurea

30
Q

What class II anti-neoplastic drug kills cells in the G2 phase of the cell cycle?

A

Bleomycin

Etoposide

Paclitaxel

31
Q

What class II anti-neoplastic drug kills cells in the M phase of the cell cycle?

A

Vinblastine and Vincristine

32
Q

What is the third class of anti-neoplastic agents? How do they work? How are they given?

A

Class III: cell cycle-specific/phase nonspecific drugs

Target cells in cell-cycle without regard for specific phase of cycle (ie all dividing cells but not G0)

Given in single large doses to take advantage of their sparing effect on those normal cells that may be in Go.

33
Q

What is are three examples of class III anti-neoplastic agents? Give examples.

A

Alkylating agents: cyclophosphamide

Miscellaneous: cisplatin

Natural product: doxorubicin

34
Q

_______ agent has a better log kill effect in cell culture.

A

Alkylating agent

35
Q

How does the timing of dosing with chemotherapy impact the outcome?

A

You want to frequently dose, but not so frequently that you kill normal cells and tumor cells the same.

BUT you also don’t want to dose too infrequently, because this will allow the tumor to continue growing and progress.

36
Q

Other than frequency of dosing, what else does differential cell kill depend on?

A

The rate in recovery of normal vurses tumor cells: typically normal cells have greater potential to recover from chemo toxicity than tumor cells.

37
Q

Many anti-neoplastic drugs target _______?

A

DNA synthesis

38
Q

What are some side effects that anti-neoplastics cause?

A
  1. Hematopoietic toxicity
  2. Gastrointestinal toxicity
  3. Organ-specific effects

Alopecia, gonadal toxicity, renal toxicity, pulm toxicity, cardiotoxicity, neurotoxicity.

Found. of Path. Processes - Block 1 (18 decks)

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