Chemotherapy III

Question 1

Topoisomerase II Inhibitors: Intercalators

Answer 1

Daunomycin
Doxorubicin
Mitoxantrone
Dactinomycin

Question 2

Topoisomerase II Inhibitors:

Non-intercalators

Answer 2

Etoposide

Question 3

Topoisomerase I Inhibitors

Answer 3

Topotecan

Irinotecan

Question 4

Which drugs are cross resistant due to MDR?

Answer 4

Non-intercalating topo II inhibitors
Intercalating topo II inhibitors
Tubulin Inhibitors (alkaloids)

Question 5

What is one way to reverse MDR resistance?

Answer 5

Give drugs as continuous infusions > downregulate the P glycoprotein

Question 6

What is the P glycoprotein?

Answer 6

Membrane bound efflux pump

Question 7

Which drugs can block the efflux pump and reverse resistance?

Answer 7

Quinine
Verapamil
Cyclosporine

Question 8

Which anticancer drugs are MDR cells resistant to?

Answer 8

Vinca alkaloids (Vinblastine, Vincristine)

Anthracyclines (Daunorubicin, doxorubicin, mitroxantrone)

Epipodophyllotoxins (Etoposide, Teniposide)

Mitomycin C
Actinomycin D
Taxol
Topotecan

Question 9

Doxorubicin MOA

Answer 9

Cell cycle non-specific

Intercalates into DNA and inhibits topo II producing double stranded DNA breaks

Question 10

When should you dose reduce doxorubicin?

Answer 10

Jaundice (excreted in bile)

Question 11

Doxorubicin SE

Answer 11

Nausea, vomiting, hair loss, stomatitis

MYELOSUPPRESSION = d-l

Question 12

What can the cumulative toxicity of doxorubicin cause? What is the max life time dose?

Answer 12

Cardiomyopathy
400 mg/M^2
Schedule dependent

Question 13

What should you obtain before administering doxorubicin?

Answer 13

EJECTION FRACTION

Question 14

How can you reduce the cardiac toxicity of Doxorubicin?

Answer 14

Give longer infusion times (96 hour)

Pretreat with an iron chelator (dexrazoxane)

Question 15

Irinotecan MOA

Answer 15

Topoisomerase I inhibitor

Requires bioactivation

Question 16

When should you dose reduce Irinotecan?

Answer 16

Jaundice

Question 17

Irinotecan SE

Answer 17

Early diarrhea (during infusion or first 24 hours)

Late diarrhea (7-10 days after)

Question 18

How can you treat the early and late diarrhea of Irinotecan?

Answer 18

Early: treat with atropine (cholinergic)

Late: treat with imodium, hydration

Question 19

What genetic mutation/Syndrome will cause increase myelosuppression and diarrhea with Irinotecan?

Answer 19

UGT1A1*28
(decreases glucoronidation)
Gilbert’s Syndrome

Question 20

Irinotecan Indication

Answer 20

Colon cancer

Question 21

Bleomycin MOA

Answer 21

Cell cycle specific

Free radical damage to DNA

Question 22

When should you dose reduce bleomycin?

Answer 22

Renal insufficiency

Question 23

Which organs can inactivate Bleomycin?

Which organs cannot?

Answer 23

Liver and kidney

Lungs and Skin

Question 24

Bleomycin SE

Answer 24

Skin hyperpigmentation

PULMONARY TOXICITY = d-l
(cumulative toxicity)

Anaphylactoid reactions

Question 25

What should you monitor in a patient taking Bleomycin?

Answer 25

``` Pulmonary function (Diffusion capacity of carbon monoxide-DLCO) ``` Obtain baseline pulm function tests prior to administration

Question 26

What should you avoid administering in a patient taking Bleomycin?

Answer 26

High oxygen concentrations

Question 27

Bleomycin Indication

Answer 27

Testicular Cancer

Question 28

Hormone dependent cancers

Answer 28

Breast cancer | Prostate cancer

Question 29

Prednisone Indication

Answer 29

Myeloproliferative or Lymphoproliferative Disorders: Multipl Myeloma, Hodgkin's disease, non-hodgkin's lymphoma, leukemia (some)

Question 30

Prednisone SE

Answer 30

Weight gain, HTN, edema, carb intolerance, suppression of pituitary-adrenal axis, weakness, euphoria, increased appetite

Question 31

Dexamethasone Indications

Answer 31

Chemotherapy related nausea and vomiting (use with 5-HT3 inhibitors) Cerebral edema, spinal cord edema due to spinal cord compression

Question 32

Tamoxifen

Answer 32

Oral selective estrogen receptor modulator (SERM)

Question 33

Tamoxifen MOA

Answer 33

Agonist-antagonist with respect to estrogen receptor (antagonist in cancer cell)

Question 34

Tamoxifen SE

Answer 34

Hot flashes Thrombosis Endometrial cancer Decreases rate of bone loss

Question 35

Tamoxifen Indication

Answer 35

Prevents breast cancer in high risk women who take for 5 years

Question 36

Aromatase Inhibitors MOA

Answer 36

Rapidly decrease estrogen levels

Question 37

Aromatase Inhibitors Indication

Answer 37

Estrogen receptor positive breast cancers

Question 38

Aromatase Inhibitors SE

Answer 38

Arthralgias, bone pain, bone loss, osteoporosis, hot flashes

Question 39

Aromatase Inhibitors

Answer 39

Anastrozole, Letrozole, Exemestane

Question 40

Goal of Prostate Cancer treatment

Answer 40

decrease testosterone production > Androgen deprivation therapy

Question 41

Flutamide/ Bicalcutamide MOA

Answer 41

Inhibit cancer cell uptake of testoterone

Question 42

Leuprolide acetate MOA

Answer 42

Decrease levels of androgens by decreasing FSH and LH by using a gonadotropin releasing hormone agonist

Question 43

What can you pretreat with to avoid the tumor flare of Leuprolide acetate?

Answer 43

Flutamide | Bicualutamide

Question 44

Side effects of Androgen Deprivation Therapy?

Answer 44

``` Weakness Decreased libido Erectile dysfunction Loss of muscle mass Gynecomastia Change in body fat distribution ```