Fitz - Purine Antimetabolites & S-Phase Agents Flashcards
tx: 6MP
maintenance of remission in ALL
tx: 6TG
acute nonlymphocytic leukemia (w/ daunorubicin and cytarabine)
tx: fludarabine (2-F-araA)
CLL, hair cell leukemia, indolent NHL
tx: cladribine
hairy cell, NHL, CLL
DLT: 6MP
myelosuppresion, hepatotoxicity (jaundice)
DLT: 6TG
myelosuppression, hepatotoxicity (LT use)
DLT: 2-F-araA
myelosuppresion, opportunitstic infs, toxic fluroadenine with oral admin
DLT: cladribine
myelosuppresion, drug fever
activating enzyme of 6MP
HPRT (HPGRT)
inactivating enzymes of 6MP
TMPT and XO in the liver
6MP over exposure risk increased in pts taking
XO inhibitors - allopurinol and febuxostat
management of tumor lysis syndrome
allopurinol
s/s of tumor lysis syndrom
- hyperkalemia
- hyperphosphatemia
- hyperuricemia
drug used to manage tumor lysis syndrome via the degradation of uric acis
pegloticase
genetic variant of TPMT that has higher than normal TMPT activity
high/high (H/H)
risk and benefit of H/H variant TPMT
- benefit = lower tox
- risk = relapse
risk and benefit of L/L variant TPMT
- risk = myelosuppresion and secondary malignancy
- benefit = efficacy
MOA: 2-F-araA and cladribine
inhibition of SNA polymerase and cessation of replication by integration into DNA/RNA
pyrimidine antimetabolites that are active in the S phase
- 5FU
- capecitabine
- cyrarabine (ara-C)
- gemcitabine
folate antimetabolites that are active in the S phase
MTX, pemetrexed
purine antimetabolites that are active in the S phase
- 6MP
- 6TG
- 2-F-araA
- cladribine
most impt factor for efficacy of cell cycle specific drugs
schedule dependent
diagnostic threshold of tumor cells
10^9 (1 billion)
