Trastuzumab

• CAS Number: 180288-69-1

Trastuzumab (trade name Herceptin ®, manufacturer Roche) is a humanized monoclonal antibody that is used as a drug for certain forms of breast cancer and gastrointestinal cancer.

Trastuzumab binds to the epidermal growth factor receptor HER2/neu ( human epidermal growth factor receptor) on the cell surface of cancer cells, so that their growth is inhibited.

History

Trastuzumab was approved in 1998 in the U.S. and 2000 in the European Union for patients with metastatic breast cancer with overexpression of HER2/neu. Such an increased formation of HER2/neu occurs in about one in four breast cancer patient. The development of trastuzumab was also among other Dennis J. Slamon and Ullrich, active at this time as basic researchers in the biotech company Genentech, heavily involved. Several studies have shown that trastuzumab with HER2-positive breast cancer who have no metastases also exist in adjuvant administration, ie in women, significantly reduces the risk of relapse. Since May 2006, the use for this indication in Europe is approved.

In January 2010, the approval for the treatment of metastatic HER2 -positive gastric cancer was expanded, with trastuzumab administered in combination with capecitabine or 5- fluorouracil and cisplatin. The survival benefit with trastuzumab therapy, however, consisted only in a few weeks. Given the cost of the drug use in stomach cancer is viewed critically.

Slamons life and his efforts to explore the HER2/neu-Rezeptors and to the possibility of treatment with Herceptin have been filmed in the TV movie Living proof with Harry Connick Jr. in the lead role in 2008.

Therapy

Prior to the initiation of trastuzumab treatment of HER2 status is determined from a tissue sample in the laboratory. The detection of HER2 overexpression is mandatory. The therapy is usually in combination with other medicines.

Mechanism of action

Trastuzumab binds to the outer side of the cell growth factor receptor HER2. This leads to inhibition of tumor cell proliferation due to apoptosis or by antibody-dependent destruction of the tumor cells by the immune system. Mechanisms as will be discussed in particular four mechanisms: the recruitment of immune cells, inhibition of intracellular signal transduction, inhibition of proteolytic cleavage of HER2, and anti-angiogenic effect.

Addition to this desired effect on breast cancer cells reversible damage to the heart muscle can occur in less than 4 % of the cases, the mechanism is still unclear. Therefore, the cardiac function in patients eligible for trastuzumab therapy in question, both before start of treatment and during the treatment is constantly checked. The treatment of patients with heart failure must be carefully considered.

Administration

Trastuzumab is administered usually once a week as an infusion over 30 to 90 minutes. Since 2006, trastuzumab has also been approved for three weekly therapy. The duration of therapy in adjuvant dose is twelve months; in patients with metastatic disease, the therapy is continued at least until the recurrence of the tumor.

Trastuzumab emtansine

Since November 2013, the antibody -drug conjugate trastuzumab emtansine is (trade name Kadcyla ®) approved for treatment of patients with unresectable, locally advanced or metastatic breast cancer that is HER2 - positive, ie overexpressed the human epidermal growth factor receptor 2. The Institute for Quality and Efficiency in Health Care ( IQWiG) confirmed that an antibody -drug conjugate in April 2014 following Judgment: Evidence for substantial additional benefits.