Phase I Study of Anti–Epidermal Growth Factor Receptor Antibody Cetuximab in Combination With Radiation Therapy in Patients With Advanced Head and Neck Cancer

Abstract

Cetuximab can be safely administered with RT. The recommended dose for phase II/III studies is a loading dose of 400 to 500 mg/m(2) and a maintenance weekly dose of 250 mg/m(2).

Phase 1 study of cetuximab in combination with 5‐fluorouracil, cisplatin, and radiotherapy in patients with locally advanced anal canal carcinoma

“…5 Cetuximab (Erbitux; Merck KgaA, Darmstadt, Germany) is an immunoglobulin G1 monoclonal antibody that specifically targets EGFR, competitively inhibiting ligand binding and ligand-dependent downstream signaling. 6 Phase 1 clinical trials demonstrated the safety of cetuximab combined with CP 7 and cetuximab combined with radiation therapy 8 in SCCs other than anal carcinoma. Also, in phase 3 clinical trials, adding cetuximab to first-line chemotherapy or RT improves outcomes in various types of cancers.…”

“…METHODS: Cetuximab was administered on days 1,8,15, 29, 36, 43, and 50 (400 mg/m 2 initial dose, then 250 mg/m 2 /week) concurrent with total dose radiation of 55 to 59 Gy, both starting on day 1. Escalating doses of 5-FU (96-hour infusion) and CP (2-hour infusion), both on days 1 and 29, were administered according to the following design: starting dose level (0) 5-FU/CP 5 800/60 mg/m 2 /day and up to dose level (12) 5-FU/CP 5 1000/80 mg/m 2 /day.…”

Prognostic significance of EGFR and Her-2 in oral cavity cancer in betel quid prevalent area

“…Overexpression of EGFR and Her-2 have been reported to be associated with higher grades or reduced survival in a variety of cancers, including breast, colorectal, and head and neck cancers (for a review, see Klijn et al, 1992;Salomon et al, 1995). Several molecular therapeutic agents against EGFR or Her-2, such as Cetuximab and Herceptin, have been studied in clinical trials (Colomer et al, 2001;Robert et al, 2002). Although several studies have found overexpression of EGFR and Her-2 in head and neck cancers, the clinical relevance of the finding varies.…”

Cetuximab, a chimeric human mouse anti-epidermal growth factor receptor monoclonal antibody, in the treatment of human colorectal cancer

“…Cetuximab has a mean volume of distribution of 45.2-61.9 ml/kg, approximately equivalent to plasma volume, at intravenous doses of 20-100 mg/m 2 given at weekly intervals for 4-12 weeks, as demonstrated in two phase I studies (Folprecht et al, 2005). The major route of cetuximab clearance is through binding of the antibody to EGFR in many tissues, including the liver and the skin, which subsequently internalizes the antibody-receptor complex and removes it from circulation (Baselga et al, 2000;Robert et al, 2001;Folprecht et al, 2005). Cetuximab clearance decreases with increasing dose, indicating saturation of the metabolic pathway and nonlinear pharmacokinetics at lower doses.…”