B.32- Cancer chemotherapy I (antimetabolites) Flashcards
what do antimetabolites do?
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
list the antimetabolites
Fluorouracil (5-fu) Methotrexate 6-Mercaptopurine Cytarabine Capecitabine Pemetrexed
are the antimetabolites CCS or CCNS?
CCS (cell cycle-specific) S phase
which agent is a Purine Antimetabolite?
6-Mercaptopurine
which agents are Pyrimidine Antimetabolite?
Fluorouracil (5-FU)
Cytarabine
which agents are folate antimetabolites?
Methotrexate
Pemetrexed
Fluorouracil’s effect is enhanced with the addition of…
Folinic acid (Leucovorin)
what does Fluorourcacil do?
bioactivated to inhibit thymidylate synthase
what is the mechanism of Methotrexate?
bioactivated to inhibit dihydrofolate reductase
what is the mechanism of 6-Mercaptopurine?
competes with the purine derivatives hypoxanthine and guanine for the enzyme HGPRT
(inhibits purine metabolism)
how is methotrexate given?
orally–> for immunotherapy (10mg once a week)
parenterally–> for cancer therapy (100mg once a week)
what does cytarabine do?
inhibits DNA polymerase
what is the mechanism of Capecitabine?
bioactivated to 5-FU
how is Capecitabine given?
orally
indications for Fluorouracil
for solid tumors only! Breast cancer ovarian cancer head and neck cancer colon cancer Topical formulations--> basal cell carcinoma, keratoses, penile CIS
side effects of Fluorouracil
nausea, vomiting
myelosuppression
Alopecia
partial or total DPD deficiency (5% of patients)
what does DPD deficiency cause?
doesn’t break down nucleotides
indications for methotrexate
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)
Side effects of methotrexate
pulmonary fibrosis myelosuppression folate deficiency toxic effects to the skin, Gi mucosa alopecia Hepatotoxicity
how can the side effects of methotrexate be reduced
by administration of folinic acid (leucovorin)
what are the indications of 6-mercaptopurine?
acute leukemia
CML
immunosuppressive therapy
what are the indications for cytarabine?
AML, ALL
CML
non-Hodgkin’s lymphoma
what are the side effects of 6-Mercaptopurine?
hepatotoxicity (cholestasis, jaundice, necrosis)
Myelosuppression
why can’t we give 6-Mercaptopurine and Allopurinol together?
allopurinol inhibits 6-MP metabolism–> ↑ risk of toxicity
side effcts of cytarabine
nausea, vomiting
myelosuppression (severe granulocytopenia)
hepatotoxicity
when is Capecitabine given?
breast cancer (when metastatic disease is resistant to 1st line drugs) colon cancer
when is Capecitabine contraindicated?
in pregnancy and lactation
when is Pemetraxed given?
non-small cell lung carcinoma
mesothelioma
side effects of both capecitabine and pemetrexed
nausea, vomiting, and myelosuppression
capecitabine–> alopecia
pemetrexed –> hand-foot syndrome!
which antimetabolite agents are prodrugs?
6-MP
Cytarabine
