Cell Cycle Specific Drug Tables - Fitz

Question 1

5-Fluorouracil…active metabolites and their actions

Answer 1

FdUMP - inhibits thymidylate synthase (no dTMP)
FdUTP - insert and damage DNA
FUTP - insert and damage RNA

Question 2

Cytarabine (Ara-C)…conversion and action

Answer 2

Kinases convert to Ara-CTP, which inhibits DNA synthesis

Question 3

Gemcitabine…conversion and action

Answer 3

Kinases convert it to nucleotide analogs, which inhibit DNA synthesis

Question 4

5-FU uses

Answer 4

• Solid tumors (colorectal, breast, ovarian)

- Topical - basal cell carcinoma

Question 5

Capecitabine uses

Answer 5

Colorectal, metastatic/resistant breast

Question 6

Gemcitabine use

Answer 6

Pancreatic cancer

Question 7

Cytarabine use

Answer 7

AML (w/ 6-thioguanine, daunorubicin)

Question 8

5-FU toxicities

Answer 8

GI intolerance, mucositis, myelosuppression

Question 9

Capecitabine toxicities

Answer 9

Same as 5-FU, + hand-foot syndrome

Question 10

Gemcitabine toxicity

Answer 10

Neutropenia

Question 11

Cytarabine toxicity

Answer 11

Granulocytopenia (severe)

Question 12

MTX function

MTX(glu)n function

Answer 12

MTX = blocks DHFR, blocking thymidine, methionine and serine synthesis
MTX(glu)n = blocks GAR and AICAR transformylase, blocking purine synthesis

Question 13

Pemetrexed function

Specialty vs. MTX?

Answer 13

Thymidylate synthase and GAR transformylase inhibitor

Does NOT inhibit DHFR, circumvents MTX resistance

Question 14

Pemetrexed uses

Answer 14

Mesothelioma (w/ cisplatin), refractory NSCLC

Question 15

High dose MTX uses

Requires what?

Answer 15

CNS prophylaxis for leukemia and high-risk lymphoma

Leucovorin rescue

Question 16

Intermediate dose MTX use

Answer 16

Gestational trophoblastic disease (choriocarcinoma)

Question 17

Low dose MTX uses

Answer 17

CNS prophylaxis (intrathecal), bladder and desmoid (IV), ALL and APL (oral)

Question 18

MTX toxicities

Answer 18

BM suppression, mucositis, renal failure (high dose)

Question 19

Pemetrexed toxicities

Answer 19

BM suppression, renal failure

Question 20

6-Mercaptopurine function

Answer 20

Inhibits purine ring biosynthesis and nucleotide interconversion, disrupting DNA and RNA

Question 21

6-Thioguanine function

Answer 21

Same as 6-Mercaptopurine

Inhibits purine ring biosynthesis and nucleotide interconversion, disrupting DNA and RNA

Question 22

Fludarabine conversion and function

Answer 22

Tumor kinases convert it to nucleotide triphosphates, which insert and disrupt DNA and RNA

Question 23

Cladribine conversion and functions

Answer 23

Tumor kinases convert it to nucleotide analogs, which inhibit DNA synthesis; also inhibits ribonucleotide reductase

Question 24

6-Mercaptopurine use

Answer 24

ALL remission maintenance

Question 25

6-Thioguanine use

Answer 25

AML (w/ daunorubicin and cytarabine)

Question 26

Fludarabine use

Answer 26

CLL (or hairy cell leukemia)

Question 27

Cladribine use

Answer 27

Hairy cell leukemia (or CLL)

Question 28

6-Mercaptopurine toxicities

Answer 28

Myelosuppression; toxicity w/ allopurinol or febuxostat; hepatotoxicity

Question 29

6-Thioguanine toxicities

Answer 29

Myelosuppression, hepatotoxicity (long use)

Question 30

Fludarabine toxicities Why give IV?

Answer 30

Myelosuppression, opportunistic infections IV = avoid GI bacteria generating toxic fluroradenine

Question 31

Cladribine toxicities

Answer 31

Myelosuppression, drug fever

Question 32

Vinca alkaloid function

Answer 32

Inhibit tubulin polymerization, causing microtubule shortening and M-phase disruption

Question 33

Taxane function

Answer 33

Inhibit tubulin fraying, causing microtubule lengthening and M-phase disruption

Question 34

Vinblastine uses

Answer 34

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

Question 35

Vincristine uses

Answer 35

ALL, lymphoma, neuroblastoma, Wilms, Ewings

Question 36

Vinorelbine use

Answer 36

Advanced non-small cell lung cancer (alone or w/ cisplatin)

Question 37

Paclitaxel uses

Answer 37

Solid tumors - Advanced breast and ovarian (w/ cisplatin)

Question 38

Docetaxel uses

Answer 38

Solid tumors - Advanced breast, ovarian recurrence

Question 39

Vinblastine toxicities

Answer 39

BM suppression, blisters

Question 40

Vincristine toxicities

Answer 40

Neurotoxicity, peripheral neuropathy, ileus, blisters

Question 41

Vinorelbine toxicities

Answer 41

BM suppression, blisters

Question 42

Paclitaxel toxicities Requires what?

Answer 42

Neutropenia, thrombocytopenia, peripheral neuropathy, hypersensitivity during infusion Needs anti-histamine and corticosteroid pretreatment

Question 43

Docetaxel toxicities

Answer 43

Neutropenia, peripheral neuropathy

Question 44

Etoposine and Teniposide - function

Answer 44

Topoisomerase 2 inhibitors, causing DNA double strand breaks

Question 45

Irinotecan and Topotecan - function

Answer 45

Topoisomerase 1 inhibitors, causing DNA single strand breaks

Question 46

Etoposide uses

Answer 46

Oat cell carcinoma of lung, testicular cancer (w/ cisplatin and bleomycin)

Question 47

Teniposide uses

Answer 47

Glioma, neuroblastoma

Question 48

Irinotecan use

Answer 48

Metastatic colorectal cancer

Question 49

Topotecan use

Answer 49

2nd line treatments for various failed 1st treatments

Question 50

Etoposide toxicities

Answer 50

Leukopenia, secondary leukemia (DNA repair error)

Question 51

Teniposide toxicity

Answer 51

Leukopenia

Question 52

Irinotecan toxicities Requires what?

Answer 52

Severe diarrhea (life-threatening), myelosuppression Loperamide co-treatment (for diarrhea)

Question 53

Topotecan toxicities

Answer 53

Neutropenia, mucositis

Question 54

Bleomycin function

Answer 54

Fe(3+)-mediated free radical damage to DNA

Question 55

Dactinomycin function

Answer 55

DNA intercalating agents

Question 56

Doxorubicin, Daunorubicin, Epirubicin - functions

Answer 56

- Inhibit topoisomerase 2 - DNA intercalating agents - Free radical generation --> DNA strand breaks

Question 57

Mitoxantrone function

Answer 57

Inhibit topoisomerase 2

Question 58

Bleomycin use

Answer 58

Testicular (w/ Vinblastine, cisplatin/etoposide)

Question 59

Doxorubicin and Epirubicin - uses

Answer 59

Breast, ovarian, lung, thyroid, lymphoma, sarcoma, etc.

Question 60

Daunorubicin uses

Answer 60

AML, ALL

Question 61

Idarubicin uses

Answer 61

AML, ALL, CML blast crisis

Question 62

Mitoxantrone uses

Answer 62

Breast, prostate, NHL

Question 63

Bleomycin toxicity

Answer 63

Pulmonary fibrosis

Question 64

'rubicins and Mitoxantrone - toxicities

Answer 64

Cardiotoxicity, dilated cardiomyopathy, CHF (cumulative)