Fitz - Pyrimidine anti-metabolites

Question 1

pyrimidine anti-metabolite drugs that inhibit DNA synthesis

Answer 1

• 5 flurouracil
• capecitabine
• cytarabine (Ara-C)
• gemcitabine

Question 2

active metabolites of 5-FU

Answer 2

FdUMP, FdUTP, FUTP

Question 3

FdUMB inhibits

Answer 3

thymidylate synthase

Question 4

FdUTP and FUTP action

Answer 4

damage DNA and RNA, respectively

Question 5

oral pro-drug of 5FU

Answer 5

capecitabine

Question 6

MOA: gemcitabine

Answer 6

inhibition of DNA synthesis

Question 7

MOA: cytarabine (ara-C)

Answer 7

inhibition of DNA synthesis via competetive inhibition of DNA polymerase

Question 8

use of 5FU

Answer 8

solid tumors - colorectal and other GI, breast, ovarian cancers; topical - basal cell ca

Question 9

use of capecitabine

Answer 9

colorectal cancer, met breast cancer (res to paclitaxel/anthracycline)

Question 10

use of gemcitabine

Answer 10

pancreatic cancer

Question 11

use of ara-C

Answer 11

AML (w/ 6-thioguanine, daunorubicin)

Question 12

DLT: 5FU

Answer 12

• severe GI intolerance
• mucositis
• myelosuppresion

Question 13

DLT: capecitabine

Answer 13

• severe GI intolerance
• mucositis
• myelosuppresion
• hand-foot syndrome ***

Question 14

DLT: gemcitabine

Answer 14

myelosuppression - neutropenia

Question 15

DLT: ara-C

Answer 15

severe myelosuppresion - granulocytopenia

Question 16

site of activation of 5FU

Answer 16

inside tumor cells

Question 17

5FU acts in what phase of the cell cycle

Answer 17

S phase

Question 18

5FU>5FUdR

Answer 18

thymidine phosphorylase

Question 19

5FUdR>5FdUMP

Answer 19

thymidine kinase

Question 20

5FUdR inhibition of thymidylate synthase needs

Answer 20

folic acid

Question 21

5FUdR inhibition of thymidylate synthase causes an increase in

Answer 21

dUTP

Question 22

incorporated into RNA to cause damage

Answer 22

FUTP

Question 23

type of tumor more resistant to 5FU

Answer 23

those with higher levels of thymidylate synthase, ie ass’d with TS gene amp

Question 24

5FU is cleared by

Answer 24

liver

Question 25

slowed 5FU clearance and increased risk of toxicity is seen in pts with

Answer 25

DPYD allelic variation

Question 26

enzyme that breaks down tymine and uracil

Answer 26

DPD

Question 27

capecitabine uses what for activation

Answer 27

liver and tumor cells

Question 28

pill verion of IV 5FU with more favorable toxicity profile

Answer 28

capecitabine

Question 29

major toxicities of capecitabine

Answer 29

hand-foot syndrome and diarrhea

Question 30

AML response to ara-C depends on

Answer 30

• rate of activation by dCK

- rate of inactivation by CDA

Question 31

limits bioavailability of ara-C and gemcitabine

Answer 31

high gut and liver levels of CDA

Question 32

AEs: gemcitabine

Answer 32

drug induced fever and flu-like s/s