chemo for GI cancer Flashcards
antimetabolite agents
fluorouracil (+leucovorin)
capecitabine
gemcitabine
5FU MOA
incorporation of FdUTP into DNA interferes with DNA processing
FdUMP inhibits thymidylate synthase (TS) and depletes nucleosides needed for DNA (depletion of thymidine and dTTP)
incorporation of FUTP into RNA inhibits RNA synthesis and function
5FU ADME
metabolized to FdUMP by thymidine kinase and to FUTP and FdUTP
can cross BBB to tx brain mets
distributes into ascitic fluid and pleural effusions (increased ADR risk)
radiation synergist
leucovorin
reduced folic acid that increases binding of FdUMP to TS to increase effect but also increases toxicity (stomatitis, diarrhea, myelosuppression)
capecitabine MOA
oral prodrug of 5FU
capecitabine ADME
radiation synergist
3 step conversion to FU involves carboxyl esterase, cytidine deaminase, thymidine phosphorylase
inhibits CYP2C9 (interacts with warfarin and phenytoin)
5 FU, capecitabine ADR’s - common
myelosuppression, mucositis / stomatitis, abd pain / diarrhea, changes in nails, dermatitis / sensitivity to sunlight, conjunctival irritation, fatigue
5 FU, capecitabine ADR’s - major
palmar - plantar erythrodysesthesia (hand food syndrome), cardiac (coronary spasm), diarrhea, hyperbilirubinemia, myelosuppression
DPD deficiency can worsen ADR’s; more active at night - dose at PM
dosing 5 FU, capecitabine
FU - mg/m2 (BSA), IV bolus or continuous; possibly topical or IV solution
cap - mg/m2 (BSA), every 12 hours with food; separate from Al or Mg products and adjust for CrCl
Gemcitabine MOA
inhibits ribonucleic reductase and incorporation into DNA (resistant to DNA repair)
Gemcitabine use
pancreatic CA
Gemcitabine ADR;s
myelosuppression (thrombocytopenia > neutropenia); increased with infusions > 60 minutes flu-like symptoms rash increased serum ALT AST renal toxicity low N/V hair loss / thinning pulmonary toxicity
Gemcitabine dosing
mg/m2 (BSA)
radiation sensitizer - avoid within 7 days of SRT
synergist with cisplatin
VEGF inhibitors agents
bevacizumab
ziv-aflibercept
ramucirumab
VEGF inhibitors MOA
bind VEGF to prevent VEGFR activation (inhibit angiogenesis / normalize tumor vasculature)
VEGF inhibitors ADR;s
HTN (tx with anti HTN Rx) HA THromboembolism proteinuria / nephrotic syndrome (test UA and monitor) infusion reactions non-GI fistula
VEGF inhibitors black box warning
GI perforations / fistula
wound dehiscence (Avoid with surgery)
hemorrhage (epistaxis to hemoptosis, GI, CNS H); increased risk in NSCLC or brain mets
VEGF inhibitors dosing
B - mg/kg IV
Ziv - mg/kg IV, prior to folfiri
Ram - mg/kg IV; premedicate with IV H1 antagonist prior to infusion and dexamethasone + acetaminophen if infusion reaction has occurred before
EGFR inhibitors agents
cetuximab
panitumumab
EGFR inhibitors MOA
competitively inhibit EGF -> prevent phosphorylation and activation of TRK’s -> inhibit cell growth, mets, and signal transduction
EGFR inhibitors ADME
EGFR results in RAS wildtype mutations; mutated TRK’s are unaffected by inhibitors
EGFR inhibitors ADR’s
dermatologic - dermatitis, acneform rash, pruritus, erythema, fissures Mg wasting diarrhea intersitial lung disease infusion reactions (cetuximab more) cardiopulmonary arrest (cet only)
EGFR inhibitors dosing
cet - mg/m2 IV, initial loading dose then 2x / week; premedicat with H1 antag
pan - mg/kg IV
Tyrosine kinase inhibitors agents
erlontinib
regorafenib
erlontinib MOA
block ATP binding sites on intracellular TK domain of EGFR -> prohibit phorphorylation -> reduce growth, survival, and proliferation
erlontinib ADR - common
rash (onset 8 days) diarrhea (onset 12 days) fatigue dyspepsia / anorexia / nv dyspnea, cough stomatitis
erlontinib - major
intersitial lung disease renal fialure hepatotoxicity GI perf hemolytic anemia
erlontinib dosing
oral tabs on empty stomach
increase with current smokers
met by CYP3A4
separate from antacids and PPIs
erlontinib use
with gemcitabine for pancreatic CA
alone for NSCLC
regorafenib MOA
oral multikinase inhibitor of angiogenesis and tumor growth TK’s (VEGF, PDGFR, oncogene k’s, cKIT, REF, BRAF)
regorafenib ADR
hand-foot syndrome HTN hypo Ca, Na, P diarrhea, wt loss, nv anemia, neutropenia, proteinuria increased ast/alt GI fistula
regorafenib dosing
PO with low fat breakfast
21 days on 7 days off
CYP3A4 metabolized
hepatic dose adjustment
