Anticancer Drugs

Question 1

When are tumors most chemo-sensitive?

Answer 1

When they are small and have high growth fraction

Question 2

What is growth fraction?

Answer 2

The fraction of tumor cells that are actively dividing

Question 3

When does growth fraction increase and decrease?

Answer 3

Growth fraction decreases when tumor size becomes too large

Question 4

What is adjuvant chemotherapy?

Answer 4

After Radiation or Surgery, chemotherapy is used to kill the rapid proliferating cells (more potential to respond to chemotherapy)

Question 5

What is the name of the curve that shows the relationship between growth fraction and drug action? What does it show?

Answer 5

Gompertzian Growth curve; it show a high exponential growth fraction that, after it reaches the limit of clinical detection, plateaus to a lower growth fraction

Question 6

What is log cell kill?

Answer 6

A first-order effect; chemotherapy kills a constant fraction of tumor cells and is proportional to the total number of cells present in the tumor; need to continue to do chemotherapy for an extended period of time even when no clinical signs of disease

Question 7

What are phase non-specific drugs?

Answer 7

Drugs on cells in all phases of the cell cycle

Question 8

What are the phase specific drugs?

Answer 8

Active only on cells that are in a specific phase of the cell cycle

Question 9

What are S Phase-specific drugs? (3)

Answer 9

(1) Cytosine arabinoside
(2) Methotrexate
(3) Camptothecins (Topoisomerase I inhibitors)

Question 10

What are M Phase-specific drugs?

Answer 10

(1) Vincristine

(2) Paclitaxel

Question 11

What are Phase non-specific drugs?

Answer 11

(1) Alkylating drugs

(2) Cisplatin

Question 12

What is the Goldie-Coldman hypothesis? What is the implication of this hypothesis?

Answer 12

The frequency of drug resistance is related to the intrinsic mutation rate of a given population of cells; Even the smallest detectable cancers are likely to contain drug-resistant forms; USE MULTIPLE DRUGS with different mechanism of action

Question 13

What are the effects of resistance on the Therapeutic Index?

Answer 13

It takes a higher concentration of drug that is good for anti-cancer activity which means that there will be more toxicity associated with it

Question 14

Cyclophosphamide: Mechanism of Action

Answer 14

Crosslinks with DNA to block replication and trigger cell death

Question 15

Cyclophosphamide: Toxicities

Answer 15

(1) Myelosuppression
(2) Secondary Malignancies
(3) Bladder- hemorrhagic cystitis

Question 16

T/F Cyclophosphamide is a prodrug.

Answer 16

TRUE

Question 17

How can you eliminate hemorrhagic cystitis that is commonly caused with Cyclophosphamide?

Answer 17

(1) Hydration

(2) Masna

Question 18

Cisplatin: Mechanism of Action

Answer 18

Crosslinks with DNA to block replication and trigger cell death

Question 19

Cisplatin: Toxicities

Answer 19

(1) Peripheral neuropathy

2) Renal toxicity (major dose-limiting toxicity

Question 20

What drugs do not cause myelosuppression? Why is this important?

Answer 20

(1) Cisplatin
(2) Vincristine
(3) Imatinib
- These drugs are easily combined with others because it will not have overlapping toxicity with other chemotherapy drugs

Question 21

Topoisomerase I inhibitors (Topotecan): Mechanism of Action

Answer 21

Traps topo I-DNA complex resulting in formation of 1 DNA strand break (it inhibits the rejoining of DNA)

Question 22

Topotecan: Toxicities

Answer 22

Myelosuppression

Question 23

Topoisomerase II inhibitors (Doxorubicin and Etoposide): Mechanism of Action

Answer 23

Traps topo II-DNA complex resulting in double strand breaks in formation of DNA (inhibits rejoining the DNA)

Question 24

T/F Topoisomerase II inhibitors are S-phase specific.

Answer 24

False. They are Phase independent!

Question 25

Topoisomerase II inhibitors (Doxorubicin and Etoposide): Toxicities

Answer 25

(1) Myelosuppression

(2) Cardiotoxicity (dose-related/cumulative)- Doxorubicin

Question 26

Vincristine: Mechanism of Action

Answer 26

Interferes with the ability to synthesize new microtubules causing it to dissolve and disappear

Question 27

Vincristine: Toxicities

Answer 27

Neurotoxicity

Question 28

Paclitaxel: Mechanism of Action

Answer 28

Interferes with the ability to break down microtubles which causes long, inactive microtubules

Question 29

Paclitaxel: Toxicities

Answer 29

(1) Neurotoxicity

(2) Myelosuppression

Question 30

What are the antimetabolites?

Answer 30

(1) Methotrexate
(2) 5-fluorouracil
(3) Cytosine arabinoside

Question 31

Methotrexate: Mechanism of Action

Answer 31

• Inhibits dihydrofolate reductase (DHFR)

- Folate pathway important for synthesis of thymidine and purines–cause block in DNA synthesis

Question 32

Methotrexate: Toxicities

Answer 32

(1) Myelosuppression

2) Mucositis (GI

Question 33

5- flurouracil: Mechanism of Action

Answer 33

Inhibits the synthesis of thymidine by thymidylate synthase (causes blockade in DNA synthesis)

Question 34

T/F 5-fluorouracil is a prodrug.

Answer 34

TRUE; thymidine analogue

Question 35

5-fluorouracil: Toxicities

Answer 35

(1) Myelosuppression

2) Mucositis (GI

Question 36

Cytosine Arabinoside: Mechanism of Action

Answer 36

Inhibits DNA polymerase and DNA synthesis

Nucleoside analogue: prodrug

Question 37

Cytosine Arabinoside: Toxicities

Answer 37

(1) Myelosuppression

Question 38

Imatinib: Mechanism of Action

Answer 38

Inhibits BCR-ABL tyrosine kinase activity present in Philadelphia chromosome (CML)

Question 39

What proliferating tissues are sensitive to cancer cells? (3)

Answer 39

(1) GI tract
(2) Hair follicles
(3) Bone marrow function (hematopoietic function)

Question 40

What are Drug toxicities associated with chemotherapy? (5)

Answer 40

(1) Bone marrow- myelosuppression
(2) Gut mucosa- mucositis
(3) Hair follicles: alopecia
(4) Germ cells- teratogenicity (temporary or permanent sterility- cyclophosphamide)
(5) Second malignancies