Function and Use of Trastuzumab

The humanized monoclonal antibody trastuzumab uses HER2 / neu as a molecular target to exert its therapeutic effect. At present, the results of multiple randomized controlled large-scale clinical trials have confirmed that the prognosis of HER2-positive breast cancer patients combined with trastuzumab in adjuvant chemotherapy is significantly improved compared with chemotherapy alone. At the same time, trastuzumab has also shown good efficacy in neoadjuvant therapy. As the first targeted drug in the field of breast cancer treatment, the emergence of trastuzumab and its clinical application is undoubtedly of epoch-making significance, which marks the more precise treatment of tumors. Although trastuzumab still has some controversies in the formulation of the joint plan, the timing of treatment and the selection of the applicable population, these problems will be solved with the deepening of research. At the same time, with the development of new targeted drugs such as lapatinib and bevacizumab (avastin), there will be more targeted drugs, which will bring more prognosis for breast cancer patients hope.

Indications

1. Metastatic breast cancer: This product is suitable for HER2 overexpressing metastatic breast cancer: as a single drug treatment of metastatic breast cancer that has received one or more chemotherapy regimens; in combination with paclitaxel or docetaxel, use In patients with metastatic breast cancer who did not receive chemotherapy.

1. Adjuvant breast cancer treatment: This single drug is suitable for adjuvant treatment of HER2 overexpressing breast cancer after surgery, adjuvant chemotherapy containing anthracycline antibiotics, and radiotherapy (if applicable).

1. Metastatic gastric cancer: This product combined with capecitabine or 5-fluorouracil and cisplatin is suitable for patients with metastatic gastric adenocarcinoma or gastroesophageal junction adenocarcinoma that has not previously received HER2 overexpression for treatment of metastatic disease. Trastuzumab can only be used in patients with HER2 overexpressing metastatic gastric cancer. HER2 overexpression is defined as the results of IHC3 + or IHC2 + / FISH + obtained using validated detection methods.

Dosage

1. Metastatic breast cancer: initial loading dose, it is recommended that the initial loading dose of this product is 4mg / kg. Intravenous infusion for more than 90 minutes; maintenance dose: the recommended weekly dose of this product is 2mg / kg. If the patient is well tolerated during the first infusion, the subsequent infusion can be changed to 30 minutes. Maintain treatment until the disease progresses. 3-week dosing regimen The initial loading dose is 8 mg / kg, followed by 6 mg / kg every three weeks. And the repeated infusion of 6mg / kg every three weeks is about 90 minutes. If the patient is well tolerated during the first infusion, the subsequent infusion can be changed to 30 minutes. Maintain treatment until disease progression.

1. Adjuvant breast cancer treatment Start trastuzumabafter completing all chemotherapy. The dosing regimen of trastuzumab is: 8 mg / kg initial loading dose followed by a maintenance dose of 6 mg / kg every 3 weeks and intravenous infusion for about 90 minutes. A total of 17 doses (a course of 52 weeks) were used.

1. Metastatic gastric cancer It is recommended to use a dosing schedule once every three weeks, with an initial loading dose of 8 mg / kg, followed by 6 mg / kg once every three weeks. The initial infusion time is approximately 90 minutes. If the patient is well tolerated during the first infusion, the subsequent infusion can be changed to 30 minutes. Maintain treatment until the disease progresses.

Pharmacological action and mechanism

Drozitumab is a recombinant DNA-derived humanized monoclonal antibody that specifically acts on the extracellular site of human epidermal growth factor receptor-2 (HER2). This antibody contains a human IgG1 framework, and the complementarity determining region is derived from the mouse anti-p185HER2 antibody, which is capable of binding to HER2. The HER2 proto-oncogene or C-erbB2 encodes a single receptor-like transmembrane protein with a molecular weight of 185 kDa, which is structurally related to the epidermal growth factor receptor. Overexpression of HER2 is observed in 25% -30% of patients with primary breast cancer. The result of HER2 gene amplification is the increased expression of HER2 protein on the surface of these tumor cells, leading to activation of the HER2 receptor. Trastuzumab has been shown to inhibit the proliferation of HER2 overexpressing tumor cells in vitro and in animal experiments. In addition, trastuzumab is a potential mediator of antibody-dependent cell-mediated cytotoxicity (ADCC). In in vitro studies, trastuzumab-mediated ADCC has been shown to be produced more preferentially in HER2 overexpressing cancer cells than HER2 non-overexpressing cancer cells.