Anti-Neoplastic Drugs Characteristics

Question 1

What are the keys in treating cancer with various drugs?

Answer 1

Clear understanding of the drug action
Harmful side effects
Modes of drug resistance
Principles for therapeutics

Question 2

What are the principles of anti-neoplasm drugs?

Answer 2

• Kill all tumor cells
• Prevent the growth of tumor cells, but not normal cells
• Increase host capacity to fight the tumor cells

Question 3

What are the problems with current anti-neoplastic drugs?

Answer 3

Poor selectivity for toxicity, based on cell kinetics
Most only affect actively dividing cells and have a narrow spectrum of activity
High chance of side effects
Possibility of secondary malignancy

Question 4

What drugs have the highest risk of secondary malignancy?

Answer 4

Highest Risk – Mechlorethamine, Etoposide, Carmustine

Moderate Risk – Doxorubicin, Cyclophosphamide, Procarbazine, Cisplatin

Question 5

What drugs have the lowest risk of secondary malignancy?

Answer 5

Vineristine
Methotrexate
Cytarabine
5-Fluorouracil

Question 6

What are the two types of anti-neoplastic drugs?

Answer 6

Cell Killing Compounds - direct killing of the cells or induce apoptosis
Cytostatic Compounds - induces terminal differentiation and interferes with growth signals

Question 7

What part of the cell cycle are the Anti-metabolites most effective?

Answer 7

S-phase when DNA is replicating.

Question 8

What types of drugs are used during the M-phase of the cell cycle?

Answer 8

Taxols and Vinca Alkaloids

Question 9

What is the log-kill mechanism for therapy?

Answer 9

A constant dose of drug kills a constant FRACTION of the tumor cells, not a certain number of them. Applies best to early stages of cancer when cells are most rapidly dividing.

Question 10

How does therapy change with size of the tumor?

Answer 10

Dose does NOT increase, the duration of therapy is what increases.

Question 11

What are the requirements for a drug therapy to be effective at curing a cancer?

Answer 11

2-4 Log-kill efficiency repeated for 4-12 cycles

Question 12

How can the frequency of dosing selectively target cancer cells?

Answer 12

The more frequent the dosing the more cancer cells can be killed, also normal cells have a faster doubling time on average compared to cancer cells, so normal cells can regenerate back to normal before the next dose of drug causing accumulation of damage to the cancer cells.

Question 13

What class are Alkylating agents in and how do they work?

Answer 13

Class I drugs, cytotoxic in a nonspecific manner.

Kills cells in any stage of cell cycle, kills normal cells and tumor cells to the same extent.

Question 14

What are the two Alkylating agents?

Answer 14

Mechlorethamine

Carmustine

Question 15

What are the type of drugs in Class III?

Answer 15

Class III: Cell cycle specific, phase specific. Given in a constant infusion, or frequent doses.

• Hormones
• Antimetabolites
• Natural Products

Question 16

What type of drugs target G2 and M-phase?

Answer 16

Natural Products.
Bleomycin and Etoposide = G2
Paclitaxel = G2
Vinblastine / Vincristine = M-phase

Question 17

What kind of drugs are Class II and how are they administered?

Answer 17

Cell Cycle specific, phase nonspecific.

• Targets dividing cells without regard to phase the cell is in.
• Administered in large doses to take advantage of cells in G0, which are not targeted (mostly normal cells).

Question 18

What drugs are apart of the Class II subtype of antineoplastics?

Answer 18

Cyclophosphamide = Alkylating Agent
Cisplatin = metal salt
Doxorubicin = natural antibiotic

Question 19

What type of drugs or Class have the highest log-kill effect?

Answer 19

Alkylating Agents, Class I

Question 20

What class and type of drugs kill the least amount of tumor cells per dose?

Answer 20

Antimetabolites - Class III

Question 21

What type of cells does Class II have difficulty killing?

Answer 21

Tumor cells that are in G0 cell cycle stage.

Cyclophosphamide, Cisplatin, and Doxorubicin

Question 22

What percent of cells would remain after a log-kill of 3?

Answer 22

99. 9% of tumor cells would be killed

0. 1% of tumor cells would remain