Cetuximab shows activity in colorectal cancer patients with tumors that do not express the epidermal growth factor receptor by immunohistochemistry

被引:888
作者
Chung, KY
Shia, J
Kemeny, NE
Shah, M
Schwartz, GK
Tse, A
Hamilton, A
Pan, D
Schrag, D
Schwartz, L
Klimstra, DS
Fridman, D
Kelsen, DP
Saltz, LB
机构
[1] Mem Sloan Kettering Canc Ctr, Gastrointestinal Oncol Serv, New York, NY 10021 USA
[2] Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10021 USA
[3] Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10021 USA
[4] Mem Sloan Kettering Canc Ctr, Dept Diagnost Imaging, New York, NY 10021 USA
关键词
D O I
10.1200/JCO.2005.08.037
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Purpose To establish evidence of activity, or lack thereof, of cetuximab-based therapy in patients with refractory colorectal cancer with tumors that do not demonstrate epidermal growth factor receptor (EGFR) expression by immunohistochemistry (IHC). Patients and Methods Pharmacy computer records were reviewed to identify all patients who received cetuximab at Memorial Sloan-Kettering Cancer Center in a nonstudy setting during the first 3 months of cetuximab's commercial availability. Medical records of these patients were then reviewed to identify colorectal cancer patients who had experienced failure with a prior irinotecan-based regimen and who had a pathology report indicating an EGFR-negative tumor by IHC. Pathology slides from these patients were reviewed by a reference pathologist to confirm EGFR negativity, and computed tomography scans during cetuximab-based therapy were reviewed by a reference radiologist. Response rates were reported using WHO criteria. Results Sixteen chemotherapy-refractory, EGFR-negative colorectal cancer patients who received cetuximab in a nonstudy setting were identified. Fourteen of these patients received cetuximab plus irinotecan, and two received cetuximab monotherapy. In the 16 patients, four major objective responses were seen (response rate, 25%; 95% CI, 4% to 46%). Conclusion Colorectal cancer patients with EGFR-negative tumors have the potential to respond to cetuximab-based therapies. EGFR analysis by current IHC techniques does not seem to have predictive value, and selection or exclusion of patients for cetuximab therapy on the basis of currently available EGFR IHC does not seem warranted. (c) 2005 by American Society of Clinical Oncology.
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页码:1803 / 1810
页数:8
相关论文
共 26 条
[1]  
[Anonymous], P AM SOC CLIN ONCOL
[2]   Immunohistochemical detection of EGFR in paraffin-embedded tumor tissues:: Variation in staining intensity due to choice of fixative and storage time of tissue sections [J].
Atkins, D ;
Reiffen, KA ;
Tegtmeier, CL ;
Winther, H ;
Bonato, MS ;
Störkel, S .
JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY, 2004, 52 (07) :893-901
[3]   HIGH-AFFINITY EPIDERMAL GROWTH-FACTOR BINDING IS SPECIFICALLY REDUCED BY A MONOCLONAL-ANTIBODY, AND APPEARS NECESSARY FOR EARLY RESPONSES [J].
BELLOT, F ;
MOOLENAAR, W ;
KRIS, R ;
MIRAKHUR, B ;
VERLAAN, I ;
ULLRICH, A ;
SCHLESSINGER, J ;
FELDER, S .
JOURNAL OF CELL BIOLOGY, 1990, 110 (02) :491-502
[4]   Anti-(epidermal growth factor) receptor monoclonal antibodies for the induction of antibody-dependent cell-mediated cytotoxicity against squamous cell carcinoma lines of the head and neck [J].
Bier, H ;
Hoffmann, T ;
Haas, I ;
van Lierop, A .
CANCER IMMUNOLOGY IMMUNOTHERAPY, 1998, 46 (03) :167-173
[5]  
CARPENTER G, 1990, J BIOL CHEM, V265, P7709
[6]  
Ciardiello F, 2001, CLIN CANCER RES, V7, P2958
[7]   Cetuximab monotherapy and cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer [J].
Cunningham, D ;
Humblet, Y ;
Siena, S ;
Khayat, D ;
Bleiberg, H ;
Santoro, A ;
Bets, D ;
Mueser, M ;
Harstrick, A ;
Verslype, C ;
Chau, I ;
Van Cutsem, E .
NEW ENGLAND JOURNAL OF MEDICINE, 2004, 351 (04) :337-345
[8]   A431-CELL VARIANTS LACKING THE BLOOD GROUP-A ANTIGEN DISPLAY INCREASED HIGH-AFFINITY EPIDERMAL GROWTH FACTOR-RECEPTOR NUMBER, PROTEIN-TYROSINE KINASE-ACTIVITY, AND RECEPTOR TURNOVER [J].
DEFIZE, LHK ;
ARNDTJOVIN, DJ ;
JOVIN, TM ;
BOONSTRA, J ;
MEISENHELDER, J ;
HUNTER, T ;
DEHEY, HT ;
DELAAT, SW .
JOURNAL OF CELL BIOLOGY, 1988, 107 (03) :939-949
[9]   SIGNAL TRANSDUCTION BY EPIDERMAL GROWTH-FACTOR OCCURS THROUGH THE SUBCLASS OF HIGH-AFFINITY RECEPTORS [J].
DEFIZE, LHK ;
BOONSTRA, J ;
MEISENHELDER, J ;
KRUIJER, W ;
TERTOOLEN, LGJ ;
TILLY, BC ;
HUNTER, T ;
HENEGOUWEN, PMPV ;
MOOLENAAR, WH ;
DELAAT, SW .
JOURNAL OF CELL BIOLOGY, 1989, 109 (05) :2495-2507
[10]  
FAN Z, 1993, CANCER RES, V53, P4322