Antineoplastics VI - Fitz

Question 1

What is the magic size of cancer cells that must have a blood supply in order to grow?

Answer 1

1-2 mm in diameter

Diffusion is no longer adequate to supply the cells with oxygen and nutrients and to take away wastes

Question 2

How do most angiogenesis inhibitors work?

Answer 2

Interfering with the actions of substances that promote angiogenesis, particularly VEGF and mTOR

Question 3

How do mTOR inhibitors work?

Answer 3

A serine/threonine kinase that reduces cell growth and proliferation, prevents angiogenesis and increases the cytotoxicity of drugs that damage DNA

Question 4

What is Rebound Angiogenesis?

Answer 4

Rapid growth of cancer when an angiogenesis inhibitor is stopped

Question 5

What is primary tumor suppression of angiogenesis elsewhere?

Answer 5

When a patient with a primary tumor only and no evidence of metastasis has the primary tumor removed and all of a sudden, metastasis occurs weeks later.

Question 6

What is the mechanism of action for mTOR inhibitors?

Answer 6

Everolimus/Temsirolium

1) Reduces Cell Growth and Proliferation
- decreased cell cycle progression (cyclin D1 regulation)
- reduced bioenergetics (decreases access to nutrients)
2) Prevents Angiogenesis
3) Synergy with Drugs that Damage DNA
- prevents p21-mediated cell cycle arrest

Question 7

How does Thalidomide work in Hansen’s Disease?

Answer 7

Suppressing Immune and Inflammatory Reactions

Question 8

What is phocomelia?

Answer 8

A congenital malformation in which the hands and feet are attached to abbreviated arms and legs

Question 9

What is the mechanism of action for Thalidomide?

Answer 9

Alters the ratios of various types of immune cells and changes in expression of molecular markers on their surface

Improves well-being and restores appetite and decreases wasting

Question 10

Why are antineoplastic agents given in combination?

Answer 10

Decreased development of resistance, synergistic effects, and decreased toxic effects

Question 11

What is pulse therapy?

Answer 11

intermittent treatment with very high doses of a drug, followed by drug-free periods to allow hematologic and immunologic recovery between treatment cycles

Question 12

What drug is given in pulses?

Answer 12

Methotrexate to treat choriocarcinoma

Question 13

What is rescue therapy?

Answer 13

Following the administration of toxic doses of chemotherapeutic agents for normal cells to be rescued by antidotes that only normal cells can use

Question 14

What drug is give as a rescue therapy?

Answer 14

Leucovorin following high dose methotrexate treatment

Question 15

What are the key principles of drug selection?

Answer 15

Active when used alone
Different MoAs or Chemical classes
CCNS vs. CCS or active in different stages of cell cycle

Question 16

What results when appropriate drug selection has occurred?

Answer 16

• Synergistic Effects
• Decreased development of resistance
• Broader cell kill in cancers that consist of a heterogeneous tumor cell population

Question 17

Define synergistic effects

Answer 17

Combined effect is greater than the sum of actions of individual drugs => lower doses => decreased toxicity

Question 18

What is an example of drugs used together for synergistic effects?

Answer 18

Cytarabine + 6-Thioguanine

Question 19

Define Recruitment

Answer 19

Use a CCNS drug to achieve significant log kill to cause cancer cells to re-enter the cell cycle, followed by administration of a CCS drug to kill the dividing cells

Question 20

What is one example of a drug regimen that uses recruitment to treat breast cancer?

Answer 20

CMF (Cyclophosphamide, Methotrexate, 5-FU)

Question 21

What is an example of drugs that use recruitment to treat AML?

Answer 21

Daunorubicin and Cytarabine

Question 22

Define Synchrony

Answer 22

Use of CCS drugs to synchronize cells into simultaneous cell division so they are more sensitive to other drugs or radiation

Question 23

What is an example of a drug that utilizes the concept of synchrony prior to administration of radiation?

Answer 23

Hydroxyurea

Question 24

What is an example of an M phase drug that uses synchrony prior to the administration of another CCS S phase drug?

Answer 24

Vinca Alkaloids followed by Etoposide

Question 25

What is an example of a drug combination that uses synchrony in the treatment of ALL?

Answer 25

Methodrexate and L-Asparaginase