Trastuzumab

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Tastuzumab, better known as Herceptin, (3bdy)

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Better Known as: Herceptin

  • Marketed By: Genentech
  • Major Indication: Breast Cancer
  • Drug Class: Human Epidermal Growth Factor Receptor 2 (HER2) Inhibitor
  • Date of FDA Approval (Discontinued): 1998 (2015)
  • 2008 Sales: $4.75 Billion
  • Importance: It is a very effective treatment against HER2-positive metastatic breast cancer compared to other cancer therapies. Controversial due to its cost of nearly $100,000 per year. Is often pointed to as an example of the benefits of personalized medicine in which a patent's genetic profile is used to optimize their medication regimen.
  • The following is a list of Pharmacokinetic Parameters. See: Pharmaceutical Drugs for more information

Mechanism of Action

Human Epidermal Growth Factor Receptor 2 (HER2) is overexpressed in approximately 30% of breast cancers. Upon receiving a mitogenic signal, HER2, located in the cell membrane, dimerizes and transfers signals to receptors within the cell. This activates different pathways including the PI3K pathway and MAPK pathway, promoting cellular survival and replication. Trastuzumab is a humanized monoclonal antibody that binds to the domain IV of the extracellular segment of the HER2 receptor. It has been suggested that Trastuzumab binding disrupts receptor dimerization, preventing the errant signal from being transfered. This ultimately causes cells to arrest druing the G1 phase of the cell cycle, halting cellular proliferation. [1]

Pharmacokinetics

EGFR Inhibitor Pharmacokinetics[2][3]
Parameter Trastuzumab
Tmax (hr) 1.7
Cmax (ng/ml) 203000
Bioavailability (%) 54
T1/2 (days) 27
AUC (ug/ml/hr) 45036
Clearance (L/h) .009
Dosage (mg) 250
Metabolism Unknown

References

  1. ↑ Menard S, Pupa SM, Campiglio M, Tagliabue E. Biologic and therapeutic role of HER2 in cancer. Oncogene. 2003 Sep 29;22(42):6570-8. PMID:14528282 doi:10.1038/sj.onc.1206779
  2. ↑ Leyland-Jones B, Gelmon K, Ayoub JP, Arnold A, Verma S, Dias R, Ghahramani P. Pharmacokinetics, safety, and efficacy of trastuzumab administered every three weeks in combination with paclitaxel. J Clin Oncol. 2003 Nov 1;21(21):3965-71. Epub 2003 Sep 24. PMID:14507946 doi:10.1200/JCO.2003.12.109
  3. ↑ B. Leyland-Jones, et al. Pharmacologic insights into the future of trastuzumab. Annals of Oncology 12 (Suppl. I): S43-S47, 2001.


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