Chemo Lecture 3-4: Antimitotic and G/M phase drugs- Fitzpatrick

Question 1

List classes of antineoplastic drugs that are antimitotic drugs

Answer 1

• Vinca alkaloids

- Taxanes

Question 2

List the drugs that are vinca alkaloids

Answer 2

• Vinblastine
• Vincristine
• Vinorelbine

Question 3

List drugs that are taxanes

Answer 3

• Taxol (paclitaxel)

- Taxotere (docetaxel)

Question 4

MOA of Vinca Alkaloids

Answer 4

Binds to beta tubulin at forming end (+) of microtubules and inhibit tubulin polymerization –> block assembly of microtubules –> inhibit microtubule elongation: rate of depolymerization (fraying&raquo_space; rate of polymerization (assembly)

Question 5

MOA of taxanes

Answer 5

Binds to beta tubulin at the forming end (+) of microtubules and as the microtubule continues to form and fray, the bound taxanes reaches the fraying end (-) and inhibit fraying (disassembly) –> Enhance tubulin polymerization–> stabilize microtubules

Question 6

Therapeutic use of Vinblastine

Answer 6

• Testicular cancer (w/ bleomycin and cisplatin)
• Lymphomas
• Neuroblastoma

Question 7

Therapeutic use of Vincristine

Answer 7

• ALL (peds)
• lymphoma
• neuroblastoma
• Wilm’s tumor
• Ewing’s sarcoma

Question 8

Therapeutic use of Vinorelbine

Answer 8

Advanced NSCL cancer

Question 9

Therapeutic use of paclitaxel

Answer 9

Advanced breast and ovarian (w/ cisplatin)

Question 10

Therapeutic use of Docetaxel

Answer 10

Advanced breast, ovarian recurrence

Question 11

Taxanes in general are effective against which types of tumors, solid or liquid?

Answer 11

Solids tumors

Question 12

Dose limiting toxicity of vinblastine and vinorelbine

Answer 12

Bone marrow suppresssion; visicant-blisters

Question 13

Dose limiting toxicity of vincristine

Answer 13

Neurotoxicity; peripheral neuropathy; paralytic ileus; vesicant- blisters

Question 14

Dose limiting toxicity of paclitaxel

Answer 14

neutropenia; thrombocytopenia; peripheral neuropathy; severe hypersensitivity during infusion

Question 15

Dose limiting toxicity of docetaxel

Answer 15

neutropenia; peripheral neuropathy

Question 16

Vinca alkaloids and taxanes drugs impair spindle integrity and works during which phase of the cell cycle?

Answer 16

M phase

Question 17

If pt experiences severe neuropathy taking administering vincristine, what drug should be substituted?

Answer 17

Vinblastine

Question 18

Vinca and taxanes drugs commonly leads to multi drug resistance due to increased expression of _

Answer 18

P-glycoprotein and its enhanced extrusion of drugs from tumor cells. This is the reason for treatment failure in over 90% of pts with advanced metastatic cancer

Question 19

Monoclonal antibodies chemo drugs are NOT prone to P-glycoproteins multi drug resistance because _

Answer 19

these drugs’ mechanism of action involve the exterior cell surface

Question 20

Class of antineoplastic drugs that which are topoisomerase inhibitors

Answer 20

1. Epipodophyllotoxins

2. Camptothecins

Question 21

Antineoplastic drugs that are epipodophyllotoxins

Answer 21

• Etoposide
• Teniposide

(EET)

Question 22

Antineoplastic drugs that are camptothecins

Answer 22

• Irinotecan
• Topotecan

(CIT)

Question 23

Epipodophyllotoxins inhibits _ and causes DNA _ stand breaks

Answer 23

topoisomerase II –> double strand breaks

Question 24

Camptothecins inhibits _ and causes DNA _ strand breaks

Answer 24

Topoisomerase I –> single strand breaks

Question 25

Therapeutic use of Etoposide

Answer 25

- Oat Cell carcinoma of lung | - testicular cancer (with cisplatin and bleomycin)

Question 26

Therapeutic use of Teniposide

Answer 26

Efficacy vs glioma and neuroblastoma

Question 27

Therapeutic use of ironotecan

Answer 27

metastatic colorectal cancer

Question 28

Therapeutic use of topotecan

Answer 28

2nd line drug for various cancers -- used after 1st line has failed

Question 29

Dose limiting tox of etoposide

Answer 29

Leukopenia; secondary cancer (Leukemia)

Question 30

Dose limiting tox of teniposide

Answer 30

leukopenia

Question 31

Dose limiting tox of ironotecan

Answer 31

Severe diarrhea | myelosuppression

Question 32

Dose limiting tox of Topotecan

Answer 32

Neutropenia; mucositis

Question 33

Ironotecan and topotecan work during which phase of the cell cycle?

Answer 33

S phase

Question 34

Etoposide and Teniposide work during which phase of the cell cycle?

Answer 34

Mixed

Question 35

Classes of drugs that which causes DNA intercalation and oxidative scission

Answer 35

- Antibiotics | - Anthrocyclines

Question 36

Which antibiotics causes DNA intercalation and oxidative scission

Answer 36

Bleomycin and Dactinomycin

Question 37

Which anthrocyclines causes DNA intercalation and oxidative scission

Answer 37

- Doxorubicin - Daunorubicin - Epirubicin - Idarubucin - Mitoxanthrone

Question 38

MOA of bleomycin

Answer 38

Fe 2+/3+ mediated free radical generation --> DNA strand breaks

Question 39

MOA of dactinomycin

Answer 39

DNA intercalating agents

Question 40

MOA of Anthracyclines

Answer 40

- All except mitoxanthrone: inhibit topoisomerase II, DNA intercalating agents, free radical generation (superoxide, H2O2), all leading to DNA strand breaks - Mitoxantrone inhibits topoisomerase II --> DNA DS break

Question 41

Therapeutic use of Bleomycin

Answer 41

- Testicular cancer

Question 42

Therapeutic use of Doxorubicin and epirubicin

Answer 42

- Breast and Ovarian cancers and others

Question 43

Therapeutic use of Idarubicin

Answer 43

Leukemia (AM, ALL, CML n blast crisis)

Question 44

Therapeutic use of daunorubicin

Answer 44

Leukemia (AML, ALL)

Question 45

Therapeutic use of Mitoxantrone

Answer 45

Breast cancer among others

Question 46

Dose limiting tox of bleomycin

Answer 46

- Pulmonary fibrosis. | - Causes skin and lung damage cuz these tissues do not have enzyme hydrolase thats required to metabolize bleomycin

Question 47

Dose limiting tox of all anthrocyclines except mitoxantrone

Answer 47

Cardiotoxicity dilated cardiomyopathy, congestiv heart failure over time. Pts with risk factors are at increased risk

Question 48

Dose limiting tox of mitoxantrone

Answer 48

- similar to -rubicins

Question 49

Bleomycin and antracyclines work during which phase of cell cycle?

Answer 49

Bleomycin: S/G2 phase Antracyclines: S/G2 phase and S phase

Question 50

What drug combo is used for Hodgkin's lymphoma?

Answer 50

- Adriamycin (doxorubicin) - Bleomycin - Vinblastine - Dacarbazine ABVD

Question 51

What toxicities are associated with hodgkin's lymphoma treatment

Answer 51

The drug combo used, each drug has it's own unique tox. - Adriamycin (doxorubicin): Cardiotoxicity - Bleomycin: Pulm fibrosis - Vinblastine: peripheral neuropathy - Dacarbazine: N/V and myelosuppression

Question 52

What drug combo is used for Non-Hodgkin's Lymphoma?

Answer 52

CHOP - Cyclophosphamide - Hydroxy-daunorubin (doxorubicin) - Oncovin (vincristine) - Prednisone

Question 53

What tox are associated with non-hodgkin's lymphoma treatment

Answer 53

CHOP - Cyclophosphamide: hemorrhagic cystitis - Hydroxy-daunorubin (doxorubicin): cardiotoxicity - Oncovin (vincristine): peripheral neuropahty - Prednisone: hyperglycemia, osteopenia

Question 54

What is tumor lysis syndrome?

Answer 54

Chemotherapy induced cell death of vast numbers of tumor cells, e.g. especially in leukemia or lymphoma --> Chemicals released from dying cells into circulation --> can produce hyperuricemia & related life-threatening electrolyte complications

Question 55

In tumor lysis syndrome, how is acute nephrotoxicity produced by excessive uric acid managed?

Answer 55

Allopurinol ( a xanthine oxidase inhibitor)

Question 56

what electrolyte imbalance is seen with tumor lysis syndrome?

Answer 56

- - Hyperkalemia - Hyperphosphatemia - hypocalcemia - hyperuricemia

Question 57

Hyperuricemia associatd with malignancy (tumor lysis syndrome) can be managed by what drug?

Answer 57

Pegloticase (uric acid odixdase)