Antimitotic And G/M Phase Drugs (Fitz)

Question 1

List the anti-mitotic drugs

Answer 1

Vinca alkaloids: Vinblastine, Vincristine, Vinorelbine

Taxanes: Taxol (Paclitaxel), Taxotere (Docetaxel)

Question 2

Basic MOA of vinca alkaloids?

Answer 2

Inhibit tubulin polymerization –> block assembly of microtubules

Question 3

Basic MOA of taxanes?

Answer 3

Enhance tubulin polymerization –> stabilize microtubules

Question 4

Therapeutic uses of vinblastine?

Answer 4

Testicular cancer (w/bleomycin and cisplatin), lymphomas, neuroblastoma

Question 5

Therapeutic uses of vincristine?

Answer 5

ALL (pediatric), lymphoma, neuroblastoma, wilms tumor, ewings sarcoma

Question 6

Therapeutic use of Vinorelbine?

Answer 6

Advanced NSCL cancer (alone or with cisplatin)

Question 7

Therapeutic uses of paclitaxel?

Answer 7

Advanced breast and ovarian (with cisplatin)

Question 8

Therapeutic use of docetaxel?

Answer 8

Advanced breast, ovarian recurrence

Taxanes are effective against solid tumors

Question 9

Dose-limiting toxicity of vinblastine?

Answer 9

BM suppression, Vesicant blisters

Question 10

Dose-limiting toxicity of vincristine?

Answer 10

NEUROTOXICITY; PERIPHERAL NEUROPATHY, paralytic ileus, vesicant blisters

Question 11

Dose-limiting toxicity of vinorelbine?

Answer 11

BM suppression; vesicant-blisters

Question 12

Dose-limiting toxicity of paclitaxel?

Answer 12

Neutropenia; thrombocytopenia; peripheral neuropathy; severe hypersensitivity during infusion-requires anti histamine and corticosteroid pre-tx

Question 13

Dose-limiting toxicity of docetaxel?

Answer 13

Neutropenia; peripheral neuropathy

Question 14

Where do vinca alkaloids bind microtubules and net result?

Answer 14

At the forming (Positive) end and inhibit tubulin polymerization –> fraying continues and shortens microtubules

Question 15

Where do taxanes bind microtubules and what eventually happens?

Answer 15

Bind at the forming (Positive) end but reach the negative end and inhibit fraying –> enhances tubulin polymerization and stabilizies microtubules

Question 16

What phase of the cell cycle do vinca alkaloids and taxanes act?

Answer 16

M phase

Question 17

Adverse effects of Vincristine? What can be substituted for VIncristine d/t this severe adverse effect?

Answer 17

Vincristine-peripheral neuropathy, neuritis (worse than Vinblastine)

Vinblastine substitutes for vincristine when neuropathy is severe

Question 18

Mechanism of anti-mitotic drug resistance?

Answer 18

Tx w/vinca and taxane drugs commonly leads to MDR d/t increased expression of P-glycoprotein and its enhanced extrustion of drugs from the tumor cell

Question 19

Administration and ADME of vinca alkaloids and taxanes?

Answer 19

Administered IV

Concentrated and metabolized by liver and excreted to varying degrees in bile or feces

Question 20

Cancer drugs with mechanisms that involve __ are not prone to P-glycoprostein MDR. Important drugs in this category are monoclonal Abs

Answer 20

The exterior cell surface

Question 21

List the epipodophyllotoxin topoisomerase inhibitors and their MOA:

Answer 21

Etoposide and Teniposide

Topoisomerase II inhibition –> DNA DOUBLE strand breaks

Question 22

List the Camptothecin topoisomerase inhibitors and their MOA:

Answer 22

Irinotecan (active metabolite SN38) and Topotecan

Topoisomerase I inhibition –> DNA SINGLE strand breaks

Question 23

Therapeutic uses of Etoposide and route of administration?

Answer 23

Oat cell carcinoma of lung; testicular cancer (with cisplatin and bleomycin)

IV, PO

Question 24

Therapeutic uses of Teniposide and route of admin

Answer 24

Efficacy vs glioma and neuroblastoma

IV

Question 25

Therapeutic use of Irinotecan and route of admin?

Answer 25

Metastatic colorectal cancer IV

Question 26

Therapeutic use of Topotecan and route of admin?

Answer 26

2nd lien various-failed prior 1st line IV

Question 27

Dose-limiting toxicity of Etoposide? Metabolism?

Answer 27

Leukopenia; secondary cancer (leukemia) CYP450-liver

Question 28

Dose-limiting toxicity of Teniposide? Metabolism?

Answer 28

Leukopenia CYP450-liver

Question 29

Dose-limiting toxicity of Irinotecan? Clearance?

Answer 29

SEVERE DIARRHEA (may be life-threatending and require tx with Loperamide); myelosuppression Renal clearance

Question 30

Dose-limtiing toxicity of Topotecan? Clearance?

Answer 30

Neutropenia; mucositis Renal clearance

Question 31

List the Abx that cause DNA strand breaks by intercalation or oxidative scission

Answer 31

Bleomycin and dactinomycin

Question 32

MOA/distinction of Bleomycin?

Answer 32

Fe2+/3+ mediated free radical generation --> DNA strand breaks

Question 33

MOA/action of Dactinomycin?

Answer 33

DNA intercalating agent

Question 34

List the anthracyclines that cause DNA strand breaks by intercalation or oxidative scission

Answer 34

Doxorubicin, Daunorubicin, Epirubicin, Idarubicin, Mitoxantrone

Question 35

MOA/distinction of Doxorubicin, Daunorubicin, Epirubicin, and Idarubicin?

Answer 35

Inhibit topoisomerase II DNA intercalating agents Free radical generation --> DNA strand breaks

Question 36

Therapeutic uses of Bleomycin? Administration? Clearance?

Answer 36

Testicular cancer (with vinblastine, cisplatin or etoposide SQ, IM, IV Renal clearance

Question 37

Therapeutic use of Doxorubicin and epirubicin?

Answer 37

Wide spectrum-BREAST, OVARIAN, lung, thyroid, lymphoma, sarcoma, etc

Question 38

Therapeutic use of Daunorubicin?

Answer 38

Leukemia (AML, ALL)

Question 39

Therapeutic uses of Idarubicin? Administration? Excretion?

Answer 39

Leukemia (AML, ALL, CML and blast crisis) IV-vesicant Biliary excretion

Question 40

Therapeutic use of Mitoxantrone? Admin?

Answer 40

BREAST, prostate, NHL IV

Question 41

Dose limiting toxicity of Bleomycin?

Answer 41

PULMONARY FIBROSIS - "blemomycin lung" 5-10% develop lung toxicity. Cumulative dose-related toxicity. Lung function improves with recovery but fibrosis remains

Question 42

Dose-limtiing toxicity of Doxorubicin, Daunorubicin, Epirubicin and Idarubicin?

Answer 42

CARDIOTOXICITY, DILATED CARDIOMYOPATHY, CHF occurs over time- cumulative dose-related toxicity; myelosuppression; mucositi

Question 43

Dose-limiting toxicity of Mitoxantrone?

Answer 43

Similar to -rubicins (anthracenedione relative to anthracyclines)

Question 44

What drug, other than the anthracyclines, may cause heart dysfunctions?

Answer 44

Trastuzumab Thanks Taqui khaja

Question 45

What enzyme is absent that cannot metabolize Bleomycin that can be lead to skin and lung damage?

Answer 45

Hydrolase

Question 46

Goal of combo chemotherapy tx?

Answer 46

Avoid drug combos that have additive or synergistic toxicities on a particular organs Use drug combos that distribute toxicities among different organs

Question 47

List the ABVD regimen for Hodgkins lymphoma and toxicities of each drug

Answer 47

Adriamycin (doxorubicin)-Cardiotoxicty Bleomycin-Pulm fibrosis Vinblastine-peripheral neuropathy Dacarbazine-Nausea/vomiting, myelosuppression

Question 48

List the CHOP regimen for NHL and toxicities of each drug:

Answer 48

Cyclophosphamide-Acrolein--> hemorrhagic cystitis Doxorubicin-Cardiomyopathy Vincristine-neuropathy, constipation Prednisone-hyperglycemia, osteopenia

Question 49

Allopurinol and febuxostat inhibit what enzyme?

Answer 49

Xanthien oxidase

Question 50

Acute nephrotoxicity produced by excessive uric acid is managed by co-adminstration of ___ with any chemotherapeutic agent that produces tumor lysis syndrome

Answer 50

Allopurinol

Question 51

What happens to potassium, phosphate, calcium, and uric acid in tumor lysis syndrome?

Answer 51

HyperK Hyperphosphatemia Hypocalcemia Hyperuricemia

Question 52

Simultaneous admin of allopurionol and 6-MP chemotherapy can result in excessive exposure to 6-MP b/c it is metabolized (inactivated) by Xanthine oxidase. What can you do to avoid this problem?

Answer 52

Reduce the dose of 6-MP

Question 53

What is Pegloticase (uricase) indicated for?

Answer 53

Hyperuricemia associated with malignancy (tumor lysis syndrome) IV q 2 weeks

Question 54

List a 5-HT3 antagonist for CINV

Answer 54

Ondansetron