Part I: Introduction

Question 1

What is the rationale for anti-neoplastic drugs?

Answer 1

1. kill all tumor cells
2. suppress the growth of tumor but not normal cells
3. increase the host capacity to fight cancer

Question 2

Which drugs are at relatively high risk for causing secondary malignancies in humans?

Answer 2

Mechlorethamine
Carmustine
Etoposide

Question 3

What are the two general ways to stop tumor growth?

Answer 3

Cause cell death

Stop growth

Question 4

What are the three cellular compartments of a tumor?

Answer 4

Dividing cells – very sensitive to cancer drugs

Temporarily non-dividing cells – partially to completely insensitive to drugs, depending on class

Permanently non-dividing cells – of littler concern, except for physical presence

Question 5

What is the log cell kill hypothesis?

Answer 5

Killing of tumors follows First order kinetics:
Constant dose of drug kills a constant fraction of tumor cells – treatment that kills 90% produces 1 log kill, one that kills 99% produces 2 log kill
Tumor size does not predict dose but does predict duration of therapy
Log kill best applies to early stages of tumor growth

Question 6

What are the stages of tumor growth?

Answer 6

Stage I: tumor contained in organ of origin
Stage II: tumor metastasized regionally but is totally removable
Stage III: tumor is metastasized regionally but is not totally removable
Stage IV: tumor is metastasized beyond local area

Question 7

What is required for a chemotherapy regiment to be curative?

Answer 7

Must have a 2-4 log kill efficiency and be repeated for 4-12 cycles of therapy

Question 8

What is the total cell kill concept?

Answer 8

One surviving cell can regenerate the tumor.

The lifespan of the host is inversely related to the number of cells that survive therapeutic measure.

Question 9

Explain class I antineoplastics.

Answer 9

Cell cycle-Nonspecific drugs
Exert cytotoxicity in nonspecific manner.
Kill cells in any stage of cell cycle (even G0).
Kill normal and neoplastic cells to the same extent.

Question 10

What are some examples of class I antineoplastics?

Answer 10

Alkylating agents – Mechlorethamine and Carmustine

Question 11

Explain class II antineoplastics.

Answer 11

Cell Cycle-specific Phase-specific drugs
Most active at specific phase of cell cycle.
More cytotoxic for neoplastic cells than for normal cells.
Give by either continuous infusion or in frequent small doses.

Question 12

Name a drug that is G1 phase specific.

Answer 12

Prednisone

Question 13

Name some drugs that are S phase specific.

Answer 13

Cytarabine, Flurouracil, Methotrexate, Mercaptopurine, Hydroxyurea

Question 14

Name some drugs that are G2 phase specific.

Answer 14

Bleomycin, Etoposide, Paclitaxel

Question 15

Some some drugs that are M phase specific.

Answer 15

Vinblastine, Vincristine

Question 16

Explain Class III antineoplastics.

Answer 16

Cycle-Specific, Phase-Nonspecific drugs
Preferential killing of proliferating neoplastic cells but without regard for the phase of the cell cycle.
Administered in single large doses to take advantage of their sparing effect on those normal cells that may be in G0.
Drawback – many human solid tumors may have a lot of cancer cells in resting phase (G0)

Question 17

Name some drugs that are class III.

Answer 17

Cyclophosphamide
Cisplatin
Doxorubicin

Question 18

Which type of drugs tend to be more selective for malignant cells over normal cells?

Answer 18

Cell-cycle-specific

Question 19

How are class I and class III drugs dosed?

Answer 19

Single doses for each cycle of therapy

Question 20

How are class II drugs dosed?

Answer 20

Continuous infusion or in frequent small doses