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FPP Weeks 1 & 2 > Cancer Chemotherapy - 1 > Flashcards

Cancer Chemotherapy - 1 Flashcards

1
Q

What is the ideal anti-neoplastic?

A
  • 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
    • However no drug reaches this of course.
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2
Q

Problems with current anti-neoplastics

A
  • Poor selective toxicity
    • (Selectivity largely based on differences in cell kinetics between normal and tumor cells
    • Normal systems can withstand greater cell losses than tumors
  • Most drugs affect only actively growing cells
  • Many drugs have limited anti-tumor spectrum
  • High incidence of side effects
  • Risk for secondary malignancies
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3
Q

Two mechanisms for stopping utmor growth

A

Cell killing compounds - Direct killing via necrosis or triggering apoptosis

Cytostatic compounds - Stop growth by inducing terminal differentiation and interfering with growth signals

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4
Q

What are the phases of the cell cycle and what drugs can target during those phases?

A

Human cell cycle time: 16 to 260 hours
Bone marow and GI lining: 24 to 48 hours

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5
Q

What are the three cellular compartments of a tumor?

A
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6
Q

What is the importance of cancer stem cells?

A
  • Small compartment of tumor
  • Often quiescent (G0)
  • Resistant to chemotherapy and radiation
  • Can regenerate tumors
  • Research to see if they are an important reason for therapeutic failure/cancer recurrence.
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7
Q

What are important factors in drug resistance?

A 
Intrinsic (genetic) vs inducible (environmental)
Same drug/same class or cross-resistance
Multiple possible mechanisms
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8
Q

What is the tumor growth curve like and when is it the most sensitive?

A

Actively growing tumor cells (dividing) are most susceptible to chemo agents (e.g. leukemia, lymphoma)

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9
Q

What are the kinetics of tumor kiilling?

A

First-order

Constant dose of drug kills a constant fraction of tumor cells
Tumor size does not predict dosing but instead the duration of therapy
Log killing best applies to early stages of tumor growth

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10
Q

What is the importance of dose density (treatment interval)?

A

Shorter dosing interval results in killing more of the tumor before it has a chance to regenerate

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11
Q

Tumor killing vs. Patient survival

A
  • One surviving cell can regenerate the entire tumor
  • Patient life span is inversely related to number of cells that survive therapy

To be curative: 2-4 log-kill efficiency for 4-12 cycles of therapy
2-4 log kill efficiency is necessary to at least double the expected life-span

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12
Q

What is the definition of cell cycle-nonspecific drugs?

A

Exert non-specific cytotoxicity
Kill cells in any stage of cell cycle, including G0
Normal and neoplastic cells are equally targeted

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13
Q

What is the definition of cell cycle-specific phase-specific drugs?

A

Target specific phase of the cell cycle
Given either by continious IV or in frequent small doses

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14
Q

What is the defintion of cell cycle-specific, phase-nonspecific drugs?

A

Target cells in cell-cycle without regard for the specific phase in cell cycle (all dividing cells, but not G0)
Administered in single large doses t otake advantage of their sparing of quiescent sells

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15
Q

Mechlorethamine

(Class, Subclass, Type, Mechanism of Kill, Risk of 2o Malignancy)

A
  • Class I: Cell Cycle-Nonspecific Drugs
  • Subclass: Alkylating Agent
  • Type: Nitrogen Mustard
  • Non-specific Cytotoxicity
    • Kills at any stage (including G0)
    • Normal and Neoplastic cells
  • 2o malignancy: High Risk
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16
Q

Carmustine

(Class, Subclass, Type, Mechanism of Kill, Risk of 2o Malignancy)

A
  • Class I: Cell Cycle-Nonspecific Drugs
  • Subclass: Alkylating Agent
  • Type: Nitrosurea
  • Non-specific Cytotoxicity
    • Kills at any stage (including G0)
    • Normal and Neoplastic cells
  • 2o malignancy: High Risk
17
Q

Prednisone

(Class, Subclass, Type, Mechanism of Kill)

A
  • Class II: Cell Cycle-Specific Phase - Specific Drugs
  • Subclass: Hormone
  • Type: Corticosteroid
  • Attacks G1 Phase with greatest activity
    • Given either by continuous infusion or in frequent small doses
18
Q

Cytarabine

(Class, Subclass, Type, Mechanism of Kill, Risk of 2o malignancy)

A
  • Class II: Cell Cycle-Specific Phase - Specific Drugs
  • Subclass: Antimetabolite
  • Type: Pyrimidine Analog
  • Attacks S Phase with greatest activity
    • Given either by continuous infusion or in frequent small doses
  • 2o malignancy: Low Risk
19
Q

Fluorouracil

(Class, Subclass, Type, Mechanism of Kill, Risk of 2o malignancy)

A
  • Class II: Cell Cycle-Specific Phase - Specific Drugs
  • Subclass: Antimetabolite
  • Type: Pyrimidine Analog
  • Attacks S Phase with greatest activity
    • Given either by continuous infusion or in frequent small doses
  • 2o malignancy: Low Risk
20
Q

Methotrexate

(Class, Subclass, Type, Mechanism of Kill, Risk of 2o Malignancy)

A
  • Class II: Cell Cycle-Specific Phase - Specific Drugs
  • Subclass: Antimetabolite
  • Type: Folic Acid Analog
  • Attacks S Phase with greatest activity
    • Given either by continuous infusion or in frequent small doses
  • 2o malignancy: Low Risk
21
Q

Mercaptopurine

(Class, Subclass, Type, Mechanism of Kill)

A
  • Class II: Cell Cycle-Specific Phase - Specific Drugs
  • Subclass: Antimetabolite
  • Type: Purine Analog
  • Attacks S Phase with greatest activity
    • Given either by continuous infusion or in frequent small doses
22
Q

Hydroxyurea

(Class, Subclass, Type, Mechanism of Kill)

A
  • Class II: Cell Cycle-Specific Phase - Specific Drugs
  • Subclass: Antimetabolite
  • Type: Substituted Urea
  • Attacks S Phase with greatest activity
    • Given either by continuous infusion or in frequent small doses
23
Q

Bleomycin

(Class, Subclass, Type, Mechanism of Kill)

A
  • Class II: Cell Cycle-Specific Phase - Specific Drugs
  • Subclass: Natural Product
  • Type: Antibiotic
  • Attacks G2 Phase with greatest activity
    • Given either by continuous infusion or in frequent small doses
24
Q

Etoposide

(Class, Subclass, Type, Mechanism of Kill, Risk of 2o Malignancy)

A
  • Class II: Cell Cycle-Specific Phase - Specific Drugs
  • Subclass: Natural Product
  • Type: Antibiotic
  • Attacks G2 Phase with greatest activity
    • Given either by continuous infusion or in frequent small doses
  • 2o malignancy: High Risk
25
Q

Paclitaxel

(Class, Subclass, Type, Mechanism of Kill)

A
  • Class II: Cell Cycle-Specific Phase - Specific Drugs
  • Subclass: Natural Product
  • Type: Taxane
  • Attacks G2 Phase with greatest activity
    • Given either by continuous infusion or in frequent small doses
26
Q

Vinblastine

(Class, Subclass, Type, Mechanism of Kill, Risk of 2o malignancy)

A
  • Class II: Cell Cycle-Specific Phase - Specific Drugs
  • Subclass: Natural Product
  • Type: Mitotic Inhibitor
  • Attacks M Phase with greatest activity
    • Given either by continuous infusion or in frequent small doses
  • 2o malignancy: Low Risk
27
Q

Vincristine

(Class, Subclass, Type, Mechanism of Kill, Risk of 2o Malignancy)

A
  • Class II: Cell Cycle-Specific Phase - Specific Drugs
  • Subclass: Natural Product
  • Type: Mitotic Inhibitor
  • Attacks M Phase with greatest activity
    • Given either by continuous infusion or in frequent small doses
  • 2o malignancy: Low Risk
28
Q

Cyclophosphamide

(Class, Subclass, Type, Mechanism of Kill, Risk of 2o malignancy)

A
  • Class III: Cell Cycle-Specific, Phase-NonSpecific Drugs
  • Subclass: Alkylating Agent
  • Type: Nitrogen Mustard
  • Attacks cells within cell cycle without regard for which phase (all cells except G0)
    • Administered in a single large dose to take advantage of their sparing effect on those normal cells that may be in G0
    • 2o malignancy: Moderate Risk
29
Q

Cisplatin

(Class, Subclass, Type, Mechanism of Kill, Risk of 2o malignancy)

A
  • Class III: Cell Cycle-Specific, Phase-NonSpecific Drugs
  • Subclass: Miscellaneous
  • Type: Metal Salt
  • Attacks cells within cell cycle without regard for which phase (all cells except G0)
    • Administered in a single large dose to take advantage of their sparing effect on those normal cells that may be in G0
  • 2o malignancy: Moderate Risk
30
Q

Doxorubicin

(Class, Subclass, Type, Mechanism of Kill, Risk of 2o malignancy)

A
  • Class III: Cell Cycle-Specific, Phase-NonSpecific Drugs
  • Subclass: Natural Product
  • Type: Antibiotic
  • Attacks cells within cell cycle without regard for which phase (all cells except G0)
    • Administered in a single large dose to take advantage of their sparing effect on those normal cells that may be in G0
  • 2o malignancy: Moderate Risk
31
Q

Antineoplastic Drugs Toxicities and Side Effects

A
  1. Hematopoietic toxicity
  2. Gastrointestinal toxicity
  3. Organ-specific Toxicity:
    • Alopecia
    • Gonadal toxicity
    • Pulmonary damage
    • cardiotoxicity

FPP Weeks 1 & 2 (18 decks)

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