Intracellular poisons 3

Question 1

What is doxorubicin and what is its major use?

Answer 1

It is a topoisomerase inhibitor (Topo 2)

• it fights against breast cancer and other solid tumors, lymphomas and leukemias
• very broad spectrum anti-cancer
• also generates free radicals
• small molecule

Question 2

What are some common DLTs of doxorubicin?

Answer 2

Stomatitis and myelosuppression

• after years can cause cardiac damage
• strong vesicant (causes blisters) must be given via central line

Question 3

What is given in order to mitigate the cardiac toxicity of doxorubicin?

Answer 3

Give Dexrazoane which is an iron chelating agent

Question 4

what is the lifetime dose of Doxorubicin?

Answer 4

less than 300 mg/m2

typical 5 cycles for breast cancer dose

Question 5

What is the cardiac toxicity of doxorubicin?

Answer 5

Dilated cardiomyopathy

Question 6

What is Etoposide?

Answer 6

Topo 2 inhibitor

• small molecule
• broad spectrum anti-cancer

Question 7

what does Etoposide fight against?

Answer 7

Germ cell tumors

• Agressive lymphomas
• small cell lung cancers
• leukemias

Question 8

What are the side effects of Etoposide?

Answer 8

Myelosuppresion and alopecia

• can cause acute leukemia in 2-3/1000 at 2-3 yr latency
• these leukemias are usually fatal

Question 9

What is Paclitaxel?

Answer 9

Anti-tubulin

• small molecule
• broad spec

Question 10

What is paclitaxel and other taxols used for?

Answer 10

Ovarian and breast carcinomas

- Epithelial malignancies

Question 11

What are the adverse effects of Paclitaxel and other taxols?

Answer 11

Myelosuppresion, neuropathy and hypersensitivity

-dlt is neuropathy

Question 12

How does Paclitaxel and other taxols work?

Answer 12

Hyper-stablizes polymerized microtubules in M phase by binding the inner surface of microtubule where GDP binds to the beta subunit

• preventing depolymerization
• cell cannot go to anaphase

Question 13

What are some other microtubules drugs?

Answer 13

Vincristine (Vinca Alkaloids)
Eribulin
Halichondrin B

Question 14

What is combined with paclitaxel for regimen for solid tumors?

Answer 14

Carboplatin

Question 15

How do Vinca alkaloids work?

Answer 15

Bind Beta-tubulin and inhibit polymerization into microtubules preventing mitotic spindle formation

Question 16

What is the DLT of Vinca alkaloids?

Answer 16

Neuropathy (Long axon transport need microtubules for function)
——– areflexia and peripheral neuritis

Constipation

Question 17

Are vinca alkaloids myelosuppressive?

Answer 17

NO

Question 18

How does Eribulin work?

Answer 18

Binds to + end of microtubule preventing elongation

Question 19

What is the DLT of Eribulin?

Answer 19

Like most anti-microtubules = neuropathy

• myelosuppression is dose limited
• $7,600/month where pac is $100/month

Question 20

What is Bortezomib?

Answer 20

Proteasome inhibitor

- small molecule

Question 21

What is Bortezomib most common fight against?

Answer 21

Multiple myeloma

• mantle cell lymphoma
• Waldenstrom’s
• B-cell malignancies

Question 22

What is the MOA of Bortezomib?

Answer 22

Blocks 26s proteasome proteolytic activity (a threonine protease)

• last 24 hrs after single dose
• IV or subcue

Question 23

What are the DLT’s of Bortezomib?

Answer 23

Fatigue
Neuropathy
Myelosuppresion

Question 24

What are the Camptothecins?

Answer 24

Camptothecin
Irinotecan
Topotecan

Question 25

What is the MOA of Irinotecan?

Answer 25

Topo 1 inhibitor - its active metabolite SN-38 can be liverated by ubiquitous hydrolytic enzymes either inside or outside clells - p-450 - turned back to SN-38 by gut flora and SN-38G

Question 26

Shat does irinotecan rely on for activty?

Answer 26

Intact lactone ring

Question 27

What does irinotecan fight against?

Answer 27

Colon cancer and GI cancers

Question 28

What is the DLT of Ironotecan?

Answer 28

Diarrhea | - drug can be given for extended periods