Cancer chemotherapy and Anti-neoplastics--Antimitotic and G/M phase drugs

Question 1

Antimitotic drugs- classes, distinction

Answer 1

• Vinca alkaloids- inhibit tubulin polymerization (block assembly of MTs)
• Taxanes- enhance tubulin polymerization (stabilize MTs)

Question 2

Vinca alkaloids- drugs

Answer 2

• VINblastine
• VINcristine
• VINorelbine

Question 3

Taxanes- drugs

Answer 3

• TAXol

- TAXotere

Question 4

Vinblastine- therapeutic uses

Answer 4

-testicular cancer (with bleomycin and cisplatin), lymphomas, neuroblastoma

Question 5

Vincristine- therapeutic uses

Answer 5

-ALL (pediatric), lymphoma, neuroblastoma, Wilms tumor, Ewings sarcoma

Question 6

Vinorelbine- therapeutic uses

Answer 6

-advanced non small cell lung cancer

Question 7

Paclitaxel- therapeutic uses

Answer 7

-breast and ovarian (with cisplatin)

Question 8

Docetaxel- therapeutic uses

Answer 8

-breast, ovarian

also solid tumors

Question 9

Vincristine- dose limiting toxicity

Answer 9

-neurotoxicity, peripheral neuropathy

Question 10

Vinca alkaloids- moa

Answer 10

• inhibit tubulin polymerization!
• bind to B tubulin on forming end of MTs (positive end)
• fraying (neg end) continues- shortening MTs!!

Question 11

Taxanes- moa

Answer 11

• stabilize MTs!!
• bind to B tubulin at forming end of MTs
• taxanes reach the negative end and inhibit fraying- enhance tubulin polymerization and stabilize MTs!!!

Question 12

Vinca alkaloids and Taxanes- what cell cycle?

Answer 12

-M phase (mitosis)

Question 13

Antimitotic drugs- adverse effects

Answer 13

• peripheral neuropathy- esp Vincristine!!

- Vinblastine substitutes for vincristine when neuropathy is severe

Question 14

Antimitotic drugs- resistance

Answer 14

MDR due to inc expression of P-glycoprotein and its enhanced extrusion of drugs from tumor cell
-assoc with treatment failure!!
(cancer drugs with mechs that involve the exterior cell surface are not prone to P-glycoprotein MDR!- monoclonal ab’s)

Question 15

opoisomerase inhibitors (cause DNA strand breaks)- classes, distinction

Answer 15

• Epipodophyllotoxins- Topoisomerase II inhibition- DNA dbl strand breaks
• Camptothecins- Topoisomerase I inhibition- DNA single strand breaks

Question 16

EpipodophylloToxins- drugs

Answer 16

-Etoposide
-Teniposide
(ET)

Question 17

Camptothecins- drugs

Answer 17

• Irinotecan

- Topotecan

Question 18

Etoposide- therapeutic uses

Answer 18

-oat cell carcinoma of lung, testicular cancer (with cisplatin and bleomycin)

Question 19

Teniposide- therapeutic uses

Answer 19

-glioma and neuroblastoma

Question 20

Irinotecan- therapeutic uses

Answer 20

-metastatic colorectal cancer

Question 21

Topotecan- therapeutic uses

Answer 21

-2nd line various- failed prior first line

Question 22

Irinotecan- dose limiting toxicity

Answer 22

-severe diarrhea (can be life threatening!)

Question 23

Topoisomerase inhibitors- moa

Answer 23

• bind to DNA-enzyme complex and create a persistently cleavable complex
• Topoisomerase I inhibitors- S phase
• Topoisomerase II inhibitors- Mixed

Question 24

DNA intercalation and oxidative scission drugs- class, distinction

Answer 24

• Antibiotics- free radical generation- DNA strand breaks

- Anthracyclines- DNA intercalating agents, free radical generation

Question 25

Antibiotics- drugs

Answer 25

-Bleomycin

Question 26

Anthracyclines- drugs

Answer 26

-Doxorubicin -Daunorubicin -Epirubicin -Idarubicin -Mitoxantrone (DDEIM)

Question 27

Bleomycin- therapeutic uses

Answer 27

-testicular cancer (with vinblastine, cisplatin or etoposide)

Question 28

Doxorubicin, Epirubicin- therapeutic uses

Answer 28

breast, ovarian

Question 29

Daunorubicin- therapeutic uses

Answer 29

leukemia (AML, ALL)

Question 30

Idarubicin- therapeutic uses

Answer 30

leukemia (aML, ALL, CML and blast crisis)

Question 31

Mitoxantrone- therapeutic uses

Answer 31

-breast

Question 32

Bleomycin- dose limiting toxicity

Answer 32

-pulm fibrosis- "bleomycin lung"!!!!!

Question 33

Anthracyclines- dose limiting toxicity

Answer 33

cardiotoxicity, dilated cardiomyopathy, CHF!!!!!- occurs over time

Question 34

Doxorubicin (anthracyclines)- moa, toxicity

Answer 34

- intercalate b/w DNA dbl helix- disrupt DNA integrity - via Cyp450 reductase--> superoxide H2O2 * dilated cardiomyopathy, HF!!!!

Question 35

risk factors for Anthracycline cardiotoxicity

Answer 35

Bleomycin- toxicity-cumulative dose - age - preexisting CV dz - longer duration of survival- pediatric pts!!

Question 36

Bleomycin- toxicity

Answer 36

- skin and lung damage- don't have the enzyme required to metabolize the drug!!! - superoxide hydroxy radicals--> fibrosis in lungs!!!

Question 37

Causes dilated cardiomyopathy, HF?

Answer 37

-Doxorubicin (anthracyclines)

Question 38

causes pulm fibrosis?

Answer 38

Bleomycin

Question 39

ABVD regimen for hodgkin lymphoma

Answer 39

- Adriamycin (doxorubicin)- cardiotoxicity) - Bleomycin- pulm fibrosis - Vinblastine- peripheral neuropathy - Dacarbazine- N/V, myelosuppression

Question 40

CHOP regimen for non-hodgkin lymphoma

Answer 40

- Cyclophosphamide- hemorrhagic cystitis - Hydroxydaunorubicin (doxorubicin)- cardiotoxicity!!! - Oncovin (Vincristine)- peripheral neuropathy - Prednisone- hyperglycemia, osteopenia

Question 41

Tumor lysis syndrome- manage by?

Answer 41

allopurinol (xanthine oxidase inhibitor)

Question 42

Tumor lysis syndrome

Answer 42

- Hyperkalemia - Hyperphosphatemia - Hyperuricemia

Question 43

allopurinol simultaneous admin with what can cause problems?

Answer 43

6-mercaptopurine (metabolized by xanthine oxidase) | -dose must be reduced

Question 44

Tumor lysis syndrome- management with uricase

Answer 44

(pegloticase- uric acid oxidase)

Question 45

chemotherapy induced N/V by?

Answer 45

-direct activation of medullary CTZ -cell damage of GI tract- 5HT release (serotonin R antagonists should be used!)