Targeted Chemotherapy

The role of different targeted therapies in cancer treatment

  • Monoclonal antibodies (may cause acute allergic reactions)
    • Target specific antigens both endogenous & exogenous
    • Typically use unconjugated MABs  (conjugated MABs have a cytotoxic agent attached)
    • -omab: mouse
    • -ximab:  chimeric
    • -zumab:  humanized
    • -umab:  human
    • Can bind directly to a receptor or growth factor in circulation.  May have either a direct (induction of apoptosis) or indirect (ADCC) induction of cytotoxicity
    • Antiangiogenesis agents  (ex. Bevacizumab)
      • Target VEGF on cancer cells to limit the cancer cell growth
  • small molecule inhibitors
    • Tyrosine kinase inhibitors (aka -nibs) bind to other substances to trigger a series of reactions that block cell signaling & proliferation
  • Oral meds are more known to cause hand-foot syndrome, rash, edema

Mechanism of action & toxicities of various targeted agents

  • Rituximab:  binds to CD20+ antigen on B-lymphocytes (ADCC)
    • Toxicity:
      • infusion-related reactions (especially the 1st infusion)
      • Tumor lysis syndrome (massive amount of lysis occurs resulting in electrolyte abnormalities)
      • Possible anaphylactic reactions (pretreat w/ APAP & benadryl
  • Ibritumomab tiuxetan:  binds to CD20+ antigen on B cells.  Tiuxetan binds to In-111 & Y-90 resulting in cellular damage
    • Toxicities: thrombocytopenia, neutropenia
  • Tositumomab:  binds to CD20+ cells (linked to I-131)
    • Toxicities:  give a thyroid-protective agent such as K-iodide drops at lease once a day prior to giving it.  Also need to pre-medicate w/ APAP & bendadryl
      • Other SE:  prolonged pancytopenia, prego category X, secondary malignancies
  • Ofatumumab:  binds to CD20+ antigen on B cells causing B cell lysis
    • Toxicities:  severe infusion reactions, prolonged thrombocytopenia & neutropenia, reactivation of Hep B, intestinal obstruction, severe infections
  • Alemtuzumab:  binds to CD52+ on malignant lymphocytes
    • IV infusion 3x/week for 12 weeks
    • Premedicate w/ APAP & benadryl for infusion related reactions.  May use HCT for severe events
    • Toxicities:  prolonged immunosuppression
      • Use bactrim & valtrex for HSV & PCP prophylaxis
      • Use ganciclover for CMV reactivation
  • Bevacizumab:  antiangiogenesis agent that binds to VEGF in circulation (VEGF ligand binding antibody)
    • Toxicities are all associated w/ what happens when you inhibit angiogenesis:  GI perforation, delayed wouund healing, HTN, bleeding, etc
  • Cetuximab (think martha stewart):  binds to EGFR thus preventing EGFR from binding to cancer cell & doing signal transduction
    • Toxicity:  acneiform skin rash (starts w/in 1st week–more severe the rash, the better the prognosis), infusion-related reactions, N/V, mucositis
  • Panitumumab:  binds to EGFR similar to cetuximab
  • Trastuzumab:  binds to HER-2/NEU (oncogene overexpressed in 25% of breast cancer)
    • Dose limiting SE:  CV
    • Other toxicities:  infusion reactions, rash, myelosuppression
  • Bortexomib:  proteosome inhibitor (inhibitor of NF-kB)
    • Toxicities:  thrombocytopenia
    • Neuropathies
  • Gefitinib & relotinib:  tyrosine kinase inhibitors that inhibit the phosphorylation of EGFR (think rash)
    • Toxicities:  diarrhea, rash, interstitial lung disease, CYP3A4 inhibition (increased INR)
  • Imatinib mesylate:  inhibits BCR-ABL tyrosine kinase (stops proliferation)
    • Toxicities:  CYP3A4 inhibitor, myelosuppression, n/v, edema, myalgias
  • Dastinib & nilotinib:  BCR-ABL tyrosine kinase inhibitors
    • Toxicities:  same as imatinib but you you also can’t use w/ PPIs or H2RA, black box warning for QT prolongation
  • Lapatinib:  inhibits HER2/Neu phosphorylation
    • Toxicities: hand-foot syndrome, GI, interstitial lung disease, LVEF decreases, QT prolongation, CYP3A4
  • Subitinib malate:  inhibits numerous TKs including VEGF, & platelet derived GF (used for renal cell carcinoma)
    • Toxicities:  GI, skin discoloration, CYP3A4, hypothyroidism
  • Sorafenib:   inhibits numerous TKs including VEGF, & platelet derived GF (used for renal cell carcinoma)
    • Toxicities:  hand-foot syndrome, GI, CYP3A4
  • Pazopanib:  binds to numerous TKs (renal cell)
    • Toxicities:  hepatotoxicity, prolonged QT, hemorrhagic events, HTN, hypothyroidism, GI perforations
  • Temsirolimus & everolimus:  small molecule inhibitors of mTOR (stops angiogenesis & the cell cycle)
    • Toxicities:  hypersensitivity reactions, hyperglycemia, infections, interstitial lung disease, hyperlipidemia, bowel perforations, prego category D, wound healing issues, hemorrhages, 3A4 interactions

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