B.32- Cancer chemotherapy I (antimetabolites)

Question 1

what do antimetabolites do?

Answer 1

they interfere with the availability of normal purine or pyrimidine nucleotide precursors
by inhibiting their synthesis or by competing with them in DNA or RNA synthesis
maximal cytotoxic effects are in the S phase

Question 2

list the antimetabolites

Answer 2

Fluorouracil (5-fu)
Methotrexate
6-Mercaptopurine
Cytarabine
Capecitabine
Pemetrexed

Question 3

are the antimetabolites CCS or CCNS?

Answer 3

CCS (cell cycle-specific) S phase

Question 4

which agent is a Purine Antimetabolite?

Answer 4

6-Mercaptopurine

Question 5

which agents are Pyrimidine Antimetabolite?

Answer 5

Fluorouracil (5-FU)

Cytarabine

Question 6

which agents are folate antimetabolites?

Answer 6

Methotrexate

Pemetrexed

Question 7

Fluorouracil’s effect is enhanced with the addition of…

Answer 7

Folinic acid (Leucovorin)

Question 8

what does Fluorourcacil do?

Answer 8

bioactivated to inhibit thymidylate synthase

Question 9

what is the mechanism of Methotrexate?

Answer 9

bioactivated to inhibit dihydrofolate reductase

Question 10

what is the mechanism of 6-Mercaptopurine?

Answer 10

competes with the purine derivatives hypoxanthine and guanine for the enzyme HGPRT
(inhibits purine metabolism)

Question 11

how is methotrexate given?

Answer 11

orally–> for immunotherapy (10mg once a week)

parenterally–> for cancer therapy (100mg once a week)

Question 12

what does cytarabine do?

Answer 12

inhibits DNA polymerase

Question 13

what is the mechanism of Capecitabine?

Answer 13

bioactivated to 5-FU

Question 14

how is Capecitabine given?

Answer 14

orally

Question 15

indications for Fluorouracil

Answer 15

for solid tumors only! 
Breast cancer 
ovarian cancer 
head and neck cancer 
colon cancer
Topical formulations--> basal cell carcinoma, keratoses, penile CIS

Question 16

side effects of Fluorouracil

Answer 16

nausea, vomiting
myelosuppression
Alopecia
partial or total DPD deficiency (5% of patients)

Question 17

what does DPD deficiency cause?

Answer 17

doesn’t break down nucleotides

Question 18

indications for methotrexate

Answer 18

breast cancer
hand and neck cancer 
bladder cancer
primary CNS lymphoma 
non-Hodkin's lymphoma 
choriocarcinoma 
Abortifacient (with Misoprostol) 
Ectopic pregnancy management 
Autoimmune/inflammatory disrorders (RA,psoriasis, IBD, SLE)

Question 19

Side effects of methotrexate

Answer 19

pulmonary fibrosis
myelosuppression 
folate deficiency
toxic effects to the skin, Gi mucosa
alopecia
Hepatotoxicity

Question 20

how can the side effects of methotrexate be reduced

Answer 20

by administration of folinic acid (leucovorin)

Question 21

what are the indications of 6-mercaptopurine?

Answer 21

acute leukemia
CML
immunosuppressive therapy

Question 22

what are the indications for cytarabine?

Answer 22

AML, ALL
CML
non-Hodgkin’s lymphoma

Question 23

what are the side effects of 6-Mercaptopurine?

Answer 23

hepatotoxicity (cholestasis, jaundice, necrosis)

Myelosuppression

Question 24

why can’t we give 6-Mercaptopurine and Allopurinol together?

Answer 24

allopurinol inhibits 6-MP metabolism–> ↑ risk of toxicity

Question 25

side effcts of cytarabine

Answer 25

nausea, vomiting
myelosuppression (severe granulocytopenia)
hepatotoxicity

Question 26

when is Capecitabine given?

Answer 26

breast cancer (when metastatic disease is resistant to 1st line drugs)
colon cancer

Question 27

when is Capecitabine contraindicated?

Answer 27

in pregnancy and lactation

Question 28

when is Pemetraxed given?

Answer 28

non-small cell lung carcinoma

mesothelioma

Question 29

side effects of both capecitabine and pemetrexed

Answer 29

nausea, vomiting, and myelosuppression
capecitabine–> alopecia
pemetrexed –> hand-foot syndrome!

Question 30

which antimetabolite agents are prodrugs?

Answer 30

6-MP

Cytarabine