Catalogo Articoli (Spogli Riviste)

OPAC HELP

Titolo:
Epidermal growth factor receptor-targeted therapy with C225 and cisplatin in patients with head and neck cancer
Autore:
Shin, DM; Donato, NJ; Perez-Soler, R; Shin, HJC; Wu, JY; Zhang, P; Lawhorn, K; Khuri, FR; Glisson, BS; Myers, J; Clayman, G; Pfister, D; Falcey, J; Waksal, H; Mendelsohn, J; Hong, WK;
Indirizzi:
Univ Texas, MD Anderson Canc Ctr, Dept Thorac Head & Neck Med Oncol, Houston, TX 77030 USA Univ Texas Houston TX USA 77030 d & Neck Med Oncol, Houston, TX 77030 USA Univ Texas, MD Anderson Canc Ctr, Dept Bioimmunotherapy, Houston, TX 77030USA Univ Texas Houston TX USA 77030 pt Bioimmunotherapy, Houston, TX 77030USA Univ Texas, MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA Univ Texas Houston TX USA 77030 c Ctr, Dept Pathol, Houston, TX 77030 USA Univ Texas, MD Anderson Canc Ctr, Dept Head & Neck Surg, Houston, TX 77030USA Univ Texas Houston TX USA 77030 pt Head & Neck Surg, Houston, TX 77030USA Univ Texas, MD Anderson Canc Ctr, Dept Expt Therapeut, Houston, TX 77030 USA Univ Texas Houston TX USA 77030 ept Expt Therapeut, Houston, TX 77030 USA Mem Sloan Kettering Canc Ctr, Dept Med Oncol, New York, NY 10021 USA Mem Sloan Kettering Canc Ctr New York NY USA 10021 New York, NY 10021 USA ImClone Syst Inc, Somerville, NJ 08876 USA ImClone Syst Inc Somerville NJUSA 08876 st Inc, Somerville, NJ 08876 USA
Titolo Testata:
CLINICAL CANCER RESEARCH
fascicolo: 5, volume: 7, anno: 2001,
pagine: 1204 - 1213
SICI:
1078-0432(200105)7:5<1204:EGFRTW>2.0.ZU;2-#
Fonte:
ISI
Lingua:
ENG
Soggetto:
SQUAMOUS CARCINOMA-CELLS; HUMAN-TUMOR CELLS; MONOCLONAL-ANTIBODIES; CHIMERIC ANTIBODY; LUNG-CANCER; PHASE-I; PROTEIN; ALPHA; COMBINATION; SENSITIVITY;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Citazioni:
34
Recensione:
Indirizzi per estratti:
Indirizzo: Shin, DM Univ Pittsburgh, Inst Canc, Div Hematol Oncol, Dept Med, 200 Lothrop St,N-755 UPMC Montefiore, Pittsburgh, PA 15213 USA Univ Pittsburgh 200 Lothrop St,N-755 UPMC Montefiore Pittsburgh PA USA 15213
Citazione:
D.M. Shin et al., "Epidermal growth factor receptor-targeted therapy with C225 and cisplatin in patients with head and neck cancer", CLIN CANC R, 7(5), 2001, pp. 1204-1213

Abstract

C225, a human-mouse chimerized monoclonal antibody directed against the epidermal growth factor receptor (EGFr), has a synergistic effect with cisplatin in xenograft models, To determine the tumor EGFr saturation dose with C225 and the fate of infused C225, we conducted a Phase Ib study,with C225 in combination with cisplatin in patients with recurrent squamous cell carcinoma of the head and neck. Using tumor samples, we assessed tumor EGFr saturation by antibody using immunohistochemistry studies, the EGFr tyrosine kinase assay, and detection of the EGFr/C225 complex formation by immunoblot. Potential candidates were screened for EGFr expression in their tumors, and 12 patients who had high levels of EGFr expression and tumors easily accessible for repeated biopsies (pretherapy, 24 h after first C225 infusion, 24 h before third C225 infusion) were entered at three different dose levelsof C225 with a fixed dose of cisplatin, The median value of tumor EGFr saturation increased to 95% at the higher dose levels. EGFr tyrosine kinase activity was significantly reduced after C225 infusion, and EGFr/C225 complexes were also detected at higher doses of C225. The Loading dose of C225 at 400 mg/m(2) with a maintenance dose at 250 mg/m(2) achieved a high percentage of saturation of EGFr in tumor tissue, and these doses were recommended for Phases II or Hi clinical trials, Sir: (67%) of nine evaluable patients achieved major responses, including two (22%) complete responses. Mild to moderate degrees of allergic reaction and folliculitis-like skin reactions were demonstrated. We conclude that infused C225 binds and significantly saturates tumor EGFr, which may render a high degree of antitumor activity, and provides a novel mechanism for targeting cancer therapy for patients who have EGFr expression in their tumors.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 13/07/20 alle ore 18:02:11