Antineoplastics for GI Cancer

Question 1

*Fluorouracil (5FU)

Answer 1

GI cancer
-antimetabolite
-Cell cycle-specific for S-phase
-Synergistic with radiation
-Can cross the blood brain barrier-Structural similarities to DNA and RNA bases
-Require metabolic activation
MOA
-Incorporation of FdUTP into DNA interferes with DNA processing (can’t appropriately replicate then)
-FdUMP inhibits thymidylate synthase (TS) and depletes nucleosides needed for DNA (most important step/compound!)
-Incorporation of FUTP into RNA inhibits RNA synthesis and function = RNA synthesis dysfunction
ADE
common - Myelosuppression, *Mucositis/ Stomatitis, Abdominal pain/ Diarrhea, Changes in finger and toe nails, Dermatitis/ sensitivity to sunlight, Conjunctival irritation, Fatigue
major - *Hand-foot syndrome (Palmar-plantar erythrodysesthesia), *DPD deficiency, cardiac toxicity (coronary spasm), Diarrhea, Hyperbilirubinemia, Myelosuppression,

Question 2

*Capecitabine

Answer 2

GI cancer
-Antimetabolite
-Oral pro-drug of fluorouracil (3 step conversion)
-*CYP 2C9 inhibitor (warfarin & phenytoin)
-may increase a person’s INR that is on warfarin
-requires dose adjustment for renal fx
ADE
common - Myelosuppression, *Mucositis/ Stomatitis, Abdominal pain/ Diarrhea, Changes in finger and toe nails, Dermatitis/ sensitivity to sunlight, Conjunctival irritation, Fatigue
major - *Hand-foot syndrome (Palmar-plantar erythrodysesthesia), *DPD deficiency, cardiac toxicity (coronary spasm), Diarrhea, Hyperbilirubinemia, Myelosuppression,

Question 3

*Leucovorin

Answer 3

GI cancer

• Reduced folic acid: folinic acid
• enhances 5FU activity
  
  • Enhances binding of FdUMP to TS
  • *Increased therapeutic effect
  • *Increased toxicity (stomatitis, diarrhea, myelosuppression

Question 4

*Bevacizumab, Ziv-Aflibercept, Ramucirumab

Answer 4

GI cancer
-VEGF Inhibitors
MOA
-*Targets vascular endothelial growth factor (VEGF)
-Binds VEGF lingand preventing binding to VEGFR
-Inhibits angiogenesis
-Normalizes tumor vasculature
ADE
-HTN, *thromboembolism, proteinuria/nephrotic syndrome, infusion rx, non-GI fistula
Black box
-GI perforations, wound dehiscence, hemorrhage

Question 5

Cetuximab, Panitumumab

Answer 5

GI cancer
-EGFR Inhibitors
-Anti-Epidermal Growth Factor Mabs
MOA
-Mab binds to EGFR and competitively inhibits the binding of EGF
-Prevents phosphorylation and activation of receptor kinases
-Inhibition of cell growth, metastasis, and signal transduction
ADE
-*Dermatologic Toxicity (rash), *Magnesium wasting, diarrhea, interstitial lung disease, infusion rx, cardiopulmonary arrest

Question 6

*Erlotinib (Tarceva),

Answer 6

GI cancer
-Tyrosine Kinase Inhibitor
-take on empty stomach
MOA
-Prohibit phosphorylation of intracellular tyrosine kinase residues by blocking ATP binding sites
ADE
-common-rash, diarrhea, fatigue, dyspepsia/anorexia, dyspnea, nausea/vomit, cough, stomatitis
-major-interstitial lung disease, renal failure, hepatotoxicity, GI perforation, hemolytic anemia