What Is Certolizumab?

This product can specifically bind to EGF receptors expressed on the surface of normal cells and various cancer cells, and competitively block the binding of EGF and other ligands, such as transforming growth factor (TGF-). This product is an IgG1 monoclonal antibody against the EGF receptor. After the two specifically bind, they inhibit the intracellular signal transduction pathway by inhibiting the tyrosine kinase (TK) binding to the EGF receptor, thereby inhibiting The proliferation of cancer cells induces apoptosis of cancer cells and reduces the production of matrix metalloproteinases and vascular endothelial growth factor.

Chinese name: Cetuximab
Foreign name: ERBITUX

Molecular structure name: Cetuximab
Chinese dosage form: injection

About Cetuximab

English product name: ERBITUX

Country of origin English medicine name: Cetuximab

Chinese reference product translation: Erbitux

Molecular Structure Name: Cetuximab

Packaging specifications and sales price: 100mg / 50ml / bottle (with filter)

Chinese dosage form: injection

100mg / 20ml / bottle (without filter)

Unit of valuation: bottle

Country of origin: Germany

Manufacturer: Mercerion Pharmaceuticals, Germany

Indication: Colorectal cancer

Expanded indications: nasopharyngeal cancer, lung cancer

Cetuximab

Cetuximab pharmacokinetic parameters

The pharmacokinetics of this product in a single-dose treatment or in combination with chemotherapy and radiation therapy are non-linear. When the dose was increased from 20 mg / m2 to 400 mg / m2, the increase in area under the curve (AUC) of the drug time exceeded the increase in dose. When the dose was increased from 20mg / m2 to 200mg / m2, the clearance (Cl) decreased from 0.08L / (m2.h) to 0.02L / (m2.h). When the dose was> 200mg / m2, Cl remained unchanged. Apparent volume of distribution (Vd) has nothing to do with the dose, it is close to 2 ~ 3L / m2.

After 400 mg / m2 instillation of this product for 2 hours, the average maximum blood concentration (Cmax) is 184 g / ml (92-327 g / ml), and the average elimination half-life (t1 / 2) is 97 hours (41-213 hours). After dripping at 250 mg / m2 for 1 hour, the average Cmax was 140 g / ml (120-170 g / ml). At the recommended dose (initial 400mg / m2, next week 250mg / m2) to the third week, the product reached steady-state blood drug concentration, with peak and valley fluctuation ranges of 168-235 and 41-85 g / ml, respectively. The average t1 / 2 is 114 hours (75 to 188 hours).

Clinical evaluation of cetuximab

A multi-center randomized phase II clinical controlled study evaluated the efficacy of this product in the treatment of metastatic colorectal cancer. Of the 329 subjects with overexpressed EGF receptor, 206 were male, with an average age of 59 (26-84 years). Of these, 58% were colon cancer patients and 40% were rectal cancer patients, of which 63% were ineffective with oxaliplatin. Patients in the study were randomly divided into 2 groups, 218 patients in combination with irinotecan and 111 patients in single use of this product. The initial dose of this product is 400 mg a week and then 250 mg a week. The treatment endpoint is disease progression or intolerable adverse reactions. Irinotecan is used at a dose of 350 mg / m2 every 3 weeks, 180 mg / m2 every 2 weeks, or 125 mg / m2 4 times in the 6th week. The results showed that the effective rates of the combined treatment group and the monotherapy group were 22.9% and 10.8%, respectively. The average duration of efficacy was 5.7 and 4.2 months in the combination treatment group and the monotherapy group, respectively. Compared with the monotherapy group, the patients in the combination treatment group significantly delayed the disease progression.

Another multicenter, single-group, open-label clinical study evaluated the efficacy of 138 patients with metastatic colorectal cancer who overexpressed the EGF receptor in combination with irinotecan. All patients had previously received irinotecan treatment, of which 74 patients still had overexpression of EGF receptor after treatment. This time, I returned to a technical training class to restore 400mg, followed by 250mg a week until the disease developed intolerable adverse reactions. Irinotecan is used at a dose of 350 mg / m2 every 3 weeks, 180 mg / m2 every 2 weeks, or 125 mg / m2 4 times every 6 weeks. The total effective rate was 15%, and the average effect duration was 6.5 months, while the ineffective group was 12%, and the average effect duration was 6.7 months.

Another multi-center single-group open clinical study evaluated the efficacy of 57 patients with metastatic colorectal cancer overexpressing EGF receptor alone with this product. All patients have previously received irinotecan treatment, of which 28 patients EGF receptor was still overexpressed after receiving irinotecan. After treatment with this product, the total effective rate was 9%, of which the effective rate in the irinotecan-ineffective group was 14%, and the average time to disease progression was 1.4 and 1.3 months, respectively. The average duration of treatment in both groups was 4.2 months.

[Indications]

This product is used alone or in combination with irinotecan for the treatment of metastatic rectal cancer with epidermal growth factor (EGF) receptor overexpression and resistance to irinotecan-based chemotherapy.

Cetuximab adverse reactions

This product is well tolerated and most of the adverse reactions can be tolerated. The most common are acne-like rash, fatigue, diarrhea, nausea, vomiting, abdominal pain, fever and constipation. Other adverse reactions include decreased white blood cell count and difficulty breathing. Skin toxicity (acne-like rash, dry skin, lacerations, infections, etc.) mostly disappears naturally. A few patients may develop severe allergic reactions, infusion reactions, sepsis, pulmonary interstitial disease, renal failure, pulmonary embolism, and dehydration. Among patients receiving monotherapy of this product and combination treatment of this product with irinotecan, 5% and 10% of patients withdrew due to adverse reactions, respectively.

Cetuximab precautions

An allergy test should be performed before using this product. Intravenous injection of 20 mg of this product and observation for more than 10 minutes. Patients with positive results should be used with caution, but negative results cannot completely rule out severe allergic reactions.

This product can often cause skin toxic reactions of varying degrees. In such patients, care should be taken to avoid light during medication. No dose adjustment is required for mild to moderate skin toxic reactions, and those with severe skin toxic reactions should be reduced as appropriate.

The study found that the drug clearance rate of women was 25% lower than that of men, but the efficacy and safety were similar, and there was no need to adjust the dose according to gender. Because this product can penetrate the placental barrier, it may damage the fetus or affect the fertility of women. Therefore, pregnant women and women of childbearing age who have not taken contraceptive measures should be used with caution. Because this product can be secreted through milk, it should be used with caution in lactating women. Until the safety of this product for children has not been confirmed, children are disabled.

The incidence of severe infusion reactions was 3%, and the fatality rate was less than 0.1%. Ninety percent of them occur on first use and are characterized by sudden airway obstruction, urticaria, and hypotension. Because some infusion reactions occur in the subsequent medication stage, the medication should be administered under the supervision of a doctor. When a mild to moderate infusion reaction occurs, you can slow down the infusion rate or take antihistamines. If serious infusion reactions occur, stop the infusion immediately. Intravenous epinephrine, glucocorticoids, antihistamines and bronchodilator And oxygen therapy. Some patients should not use this product again. In addition, if acute symptoms of pulmonary symptoms occur during the use of this product, they should be discontinued immediately to find out the cause. If it is indeed a pulmonary interstitial disease, it should be disabled and treated accordingly.

Cetuximab dosage usage

The recommended starting dose is 400mg / m2, the infusion time is 120 minutes, and the drip rate should be controlled within 5ml / min. The maintenance dose is 250mg / m2 per week, and the infusion time is not less than 60 minutes. Early administration of H1 receptor blockers has a certain effect on preventing infusion reactions. Do not shake or dilute before use.

[Specifications] 100mg per 50ml

[Storage] It can be stored for more than 12 hours at 2 8 , and more than 8 hours at 20 25 .