Chemo Drugs II: Hormonal Agents and Intercalating Agents

Question 1

Doxorubicin and Daunomycin

MOA

Answer 1

Topoisomerase II blockers – introduce double stranded DNA breaks

Intercalates between base pairs in the DNA helix

Question 2

Function of Topoisomerase enzymes

Answer 2

Resolves conformational and topological changes (supercoils) in DNA

Cuts out the knot, then resynthesizes the part that is missing

Question 3

What drugs block topoisomerase II enzymes?

Answer 3

Doxorubicin
Daunomycin
Etoposide

Question 4

What drugs block topoisomerase I enzymes?

Answer 4

Ininotecan

Topotecan

Question 5

What is MDR? How does it work?

Answer 5

“Hydrophobic vacuum cleanser”
Pumps drugs out of the cytoplasm

MDR is found in many chemo-resistant cells

Question 6

Doxorubicin
MOA
Metabolism

Answer 6

Intercalates into DNA and inhibits topoisomerase II (introduces double stranded breaks into DNA)

Cell cycle nonspecific

Hepatically metabolized; reduce dose if patient has jaundice

Question 7

Doxorubicin

Indications

Answer 7

Lymphoma (Hodgkin or non)
Leukemia
Breast CA

Question 8

Doxorubicin
Major Toxicity
Dose for that toxicity?

Answer 8

Cardiotoxic!
Schedule-dependent toxicity
Max lifetime cumulative dose = 400 mg/m2

Cumulative toxicity that may result in dilated cardiomyopathy

Avoid doxorubicin if baseline ejection fraction is abnormal

Question 9

Irinotecan
MOA
Metabolism

Answer 9

Topoisomerase I inhibitor
-Introduces single stranded breaks into DNA

Hepatic metabolism; reduce dose in jaundice

Question 10

Irinotecan

AEs

Answer 10

Early diarrhea (cholinergic) – use atropine to prevent

Late (7-10days) diarrhea (secretory) – use imodium and hydration

Myelosuppression

Ppl with Gilbert’s disease may have inc risk of severe diarrhea and myelosuppression

Question 11

Irinotecan

Indications

Answer 11

Colon cancer treatment

Question 12

Bleomycin

MOA

Answer 12

Free radical damage to DNA

Cell cycle specific

Question 13

Bleomycin

Excretion and Metabolism

Answer 13

50% renal excretion

Liver and kidney rapidly inactivate bleomycin. Lungs and skin cannot inactivate bleomycin

Question 14

Bleomycin

AEs

Answer 14

Cumulative Pulmonary Toxicity – Rapidly fatal IPF
-Monitor baseline PFTs before tx

May cause vein hyperpigmentation

Question 15

Bleomycin

Indications

Answer 15

Testicular cancer

Question 16

When is prednisone used in cancer?

Answer 16

May be used in myeloproliferative or lymphoproliferative disorders

Question 17

Dexamethasone

Indications in cancer

Answer 17

Used with Ondansetron to lower chemo-related N/V

May also resolve cerebral or spinal cord edema

Question 18

Tamoxifen

MOA

Answer 18

SERM
Antagonist at breast ER
Agonist at bone and uterus ER

Question 19

Tamoxifen

Indications

Answer 19

ER positive breast cancer

Also prevents breast cancer in women at higher risk

Question 20

Tamoxifen

AEs

Answer 20

Hot flashes, thrombosis, endometrial hyperplasia and carcinoma

Question 21

List the Aromatase Inhibitors

Answer 21

Anastrozole
Exemestane
Letrozole

Question 22

Flutamide

MOA and Indication

Answer 22

AR receptor antagonist used in prostate cancer

Inhibits growth of prostate CA

Question 23

Leuprolide

MOA and Indication

Answer 23

Long acting GnRH agonist used to shut down the gonadal axis

Decreases testosterone production in long-term, which helps halt prostate cancer growth

Question 24

Leuprolide

What happens short-term and long-term with this drug? How can this be addressed?

Answer 24

GnRH agonist
During the first 7-10 days, leuprolide has an AGONIST effect to increase androgen production
-Initial stimulation of prostate CA cells

May cause increased bone pain (if prostate CA has metastasized to bone) and compression of tumor in epidural space

Before giving leuprolide, give pt flutamide to block AR and prevent this