P M Harari

Figure 2

Simplified schematic illustration of the EGFR pathway highlighting potential downstream cellular and tissue effects of EGFR signaling inhibition. The action site for EGFR inhibitors is depicted for mAbs and TKIs. Adapted with permission from Harari & Huang (2001).

References

↵

Aaronson SA 1991 Growth factors and cancer. Science 254 1146–1153.

↵

Abbruzzese JL, Rosenberg A, Xiong Q, LoBuglio A, Schmidt W, Wolff R, Needle M & Waksal H 2001 Phase II study of antiepidermal growth factor receptor (EGFR) antibody cetuximab (IMC-C225) in combination with gemcitabine in patients with advanced pancreatic cancer. Proceedings of the American Society of Clinical Oncology 20 130a. Abstract 518.

↵

Akita RW & Sliwkowski MX 2003 Preclinical studies with Erlotinib (Tarceva). Seminars in Oncology 30 15–24.

↵

Albanell J, Rojo F & Baselga J 2001 Pharmacodynamic studies with the epidermal growth factor receptor tyrosine kinase inhibitor ZD1839. Seminars in Oncology 28 56–66.

↵

Alroy I & Yarden Y 1997 The ErbB signaling network in embryogenesis and oncogenesis:signal diversification through combinatorial ligand–receptor interactions. FEBS Letters 410 83–86.

↵

Arteaga CL 2002 Epidermal growth factor receptor dependence in human tumors: more than just expression? Oncologist 7 (Suppl 4) 31–39.

↵

Arteaga CL & Baselga J 2003 Clinical trial design and end points for epidermal growth factor receptor-targeted therapies: implications for drug development and practice. Clinical Cancer Research 9 1579–1589.

↵

Arteaga CL & Johnson DH 2001 Tyrosine kinase inhibitors-ZD1839 (Iressa). Current Opinion in Oncology 13 491–498.

↵

AstraZeneca Pharmaceuticals LP 2003 Iressa (gefitinib) product label.

↵

Barnes CJ, Bagheri-Yarmand R, Mandal M, Yang Z, Clayman GL, Hong WK & Kumar R 2003 Suppression of epidermal growth factor receptor, mitogen-activated protein kinase, and Pak1 pathways and invasiveness of human cutaneous squamous cancer cells by the tyrosine kinase inhibitor ZD1839 (Iressa). Molecular Cancer Therapeutics 2 345–351.

↵

Baselga J 2001 The EGFR as a target for anticancer therapy — focus on cetuximab. European Journal of Cancer 37 (Suppl 4) S16–S22.

↵

Baselga J & Averbuch SD 2000 ZD1839 (‘Iressa ’) as an anticancer agent. Drugs 60 (Suppl 1) 33–40.

↵

Baselga J, Pfister D, Cooper MR, Cohen R, Burtness B, Bos M, D ’Andrea G, Seidman A, Norton L, Gunnett K, Falcey J, Anderson V, Waksal H & Mendelsohn J 2000 Phase I studies of anti-epidermal growth factor receptor chimeric antibody C225 alone and in combination with cisplatin. Journal of Clinical Oncology 18 904–914.

↵

Baselga J, Trigo JM, Bourhis J, Tortochaux J, Cortes-Funes H, Hitt R, Gascon P, Muesser M, Harstrick A & Eckardt A 2002 Cetuximab (C225) plus cisplatin/carboplatin is active in patients (pts) with recurrent/metastatic squamous cell carcinoma of the head and neck (SCCHN) progressing on a same dose and schedule platinum-based regimen. Proceedings of the American Society of Clinical Oncology 21 226a. Abstract 900.

↵

Baselga J, Albanell J, Ruiz A, Lluch A, Gascon P, Gonzalez S, Guillen V, Sauleda S, Averbuch S & Rojo F 2003 Phase II and tumor pharmacodynamic study of gefitinib (ZD1839) in patients with advanced breast cancer. Proceedings of the American Society of Clinical Oncology 22 7 Abstract 24.

↵

Bishop PC, Myers T, Robey R, Fry DW, Liu ET, Blagosklonny MV & Bates SE 2002 Differential sensitivity of cancer cells to inhibitors of the epidermal growth factor receptor family. Oncogene 21 119–127.

↵

Bonner JA, Giralt J, Harari PM, Cohen R, Jones C, Sur RK, Rabin D, Azarnia N, Needle MN & Ang KK 2004 Cetuximab prolongs survival in patients with locoregionally advanced squamous cell carcinoma of head and neck:a phase III study of high dose radiation therapy with or without cetuximab. Proceedings of the American Society of Clinical Oncology 23 Abstract 5507.

↵

Burtness BA, Li Y, Flood W, Mattar BI & Forastiere AA 2002 Phase III trial comparing cisplatin (C) + placebo (P) to C + anti-epidermal growth factor antibody (EGF-R) C225 in patients (PTS) with metastatic/recurrent head and neck cancer (HNC). Proceedings of the American Society of Clinical Oncology 21 901 Abstract.

↵

Busam KJ, Capodieci P, Motzer R, Kiehn T, Phelan D & Halpern AC 2001 Cutaneous side-effects in cancer patients treated with the antiepidermal growth factor receptor antibody C225. British Journal of Dermatology 144 1169–1176.

↵

Carpenter G 2000 The EGF receptor:a nexus for trafficking and signaling. Bioessays 22 697–707.

↵

Carpenter G & Cohen S 1990 Epidermal growth factor. Journal of Biological Chemistry 265 7709–7712.

↵

Cella D 2003 Impact of ZD1839 on non-small cell lung cancer-related symptoms as measured by the functional assessment of cancer therapy-lung scale. Seminars in Oncology 30 39–48.

↵

Chan ATC, Hsu MM, Goh BC, Hui EP, Liu TW, Millward M, Chang AY, Ma BB, Hong RL, Lin X et al. 2003 A phase II study of cetuximab (C225) in combination with carboplatin in patients with recurrent or metastatic nasopharyngeal carcinoma who failed on platinum-based chemotherapy. Proceedings of the American Society of Clinical Oncology 22 497 Abstract 2000.

↵

Cho CD, Fisher GA, Halsey J, Jambalos CN, Advani RH, Wakelee H, Lum BL & Sikic BI 2003 A phase II study of gefitinib in combination with FOLFOX-4 (IFOX) in patients with unresectable or metastatic colorectal cancer. Proceedings of the American Society of Clinical Oncology 22 265 Abstract 1062.

↵

Ciardiello F 2000 Epidermal growth factor receptor tyrosine kinase inhibitors as anticancer agents. Drugs 60 (Suppl 1) 25–32.

↵

Ciardiello F, Caputo R, Bianco R, Damiano V, Pomatico G, De Placido S, Bianco AR & Tortora G 2000 Antitumor effect and potentiation of cytotoxic drugs activity in human cancer cells by ZD-1839 (Iressa), an epidermal growth factor receptor-selective tyrosine kinase inhibitor. Clinical Cancer Research 6 2053–2063.

↵

Cohen EE, Rosen F, Dekker A, Bajda C, Stenson K, Shulman KL, Lamont E, Kozloff M & Vokes EE 2002 Phase II study of ZD1839 (Iressa) in recurrent of metastatic squamous cell carcinoma of the head and neck (SCCHN). Proceedings of the American Society of Clinical Oncology 21 225a Abstract 899.

↵

Cohen EE, Rosen F, Stadler WM, Recant W, Stenson K, Huo D & Vokes EE 2003a Phase II trial of ZD1839 in recurrent or metastatic squamous cell carcinoma of the head and neck. Journal of Clinical Oncology 21 1980–1987.

↵

Cohen EE, Stenson K, Gustin DM, Lamont E, Mauer AM, Blair E, Stadler WM, Dekker A, Mallon W & Vokes EE 2003b A phase II study of 250 mg gefitinib (ZD1839) monotherapy in recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN). Proceedings of the American Society of Clinical Oncology 22 502 Abstract 2021.

↵

Cohen RB 2003 Epidermal growth factor receptor as a therapeutic target in colorectal cancer. Clinical Colorectal Cancer 2 246–251.

↵

Cunningham D, Humblet Y, Siena S, Khayat D, Bleiberg H, Santoro A, Bets D, Mueser M, Harstrick A & Van Cutsem E 2003 Cetuximab (C225) alone or in combination with irinotecan (CPT-11) in patients with epidermal growth factor receptor (EGFR)-positive, irinotecan-refractory metastatic colorectal cancer. Proceedings of the American Society of Clinical Oncology 22 252 Abstract 1012.

↵

Dancey JE & Freidlin B 2003 Targeting epidermal growth factor receptor —are we missing the mark? Lancet 362 62–64.

↵

Davis CG, Gallo ML & Corvalan JR 1999 Transgenic mice as a source of fully human antibodies for the treatment of cancer. Cancer Metastasis Reviews 18 421–425.

↵

Dawson NA, Guo C, Zak R, Dorsey B, Smoot J, Wong J & Hussain A 2003 A phase II trial of ZD1839 in stage IV and recurrent renal cell carcinoma. Proceedings of the American Society of Clinical Oncology 22 404 Abstract 1623.

↵

Di Gennaro E, Barbarino M, Bruzzese F, De Lorenzo S, Caraglia M, Abbruzzese A, Avallone A, Comella P, Caponigro F, Pepe S et al. 2003 Critical role of both p27KIP1 and p21CIP1/WAF1 in the antiproliferative effect of ZD1839 (‘Iressa ’), an epidermal growth factor receptor tyrosine kinase inhibitor, in head and neck squamous carcinoma cells. Journal of Cellular Physiology 195 139–150.

↵

Douillard J-Y, Giaccone G, Horai T, Noda K, Vansteenkiste JF, Takata I, Gatzemeier U, Fukuoka M, Macleod A, Feyereislova A et al. 2002 Improvement in disease-related symptoms and quality of life in patients with advanced non-small-cell lung cancer (NSCLC) treated with ZD1839 (‘Iressa ’) (IDEAL 1). Proceedings of the American Society of Clinical Oncology 21 299a. Abstract 1195.

↵

Dragovich T, Patnaik A, Rowinsky EK, Karp D, Huberman M, Clinebell T, Hamilton M, Zitelli A, Nadler P & Wood DL 2003 A phase I B trial of gemcitabine and erlotinib HCl in patients with advanced pancreatic adenocarcinoma and other potentially responsive malignancies. Proceedings of the American Society of Clinical Oncology 22 223 Abstract 895.

↵

Drucker BJ, Schwartz L, Marion S & Motzer R 2002 Phase II trial of ZD1839 (Iressa), an EGF receptor inhibitor, in patients with advanced renal cell carcinoma. Proceedings of the American Society of Clinical Oncology 21 181a Abstract 720.

↵

Earp HSIII, Calvo BF & Sartor CI 2003 The EGF receptor family–multiple roles in proliferation, differentiation, and neoplasia with an emphasis on HER4. Transactions of the American Clinical and Climatological Association 114 315–333.

↵

Ennis BW, Lippman ME & Dickson RB 1991 The EGF receptor system as a target for antitumor therapy. Cancer Investigation 9 553–562.

↵

Fan Z, Shang BY, Lu Y, Chou JL & Mendelsohn J 1997 Reciprocal changes in p27(Kip1) and p21(Cip1) in growth inhibition mediated by blockade or overstimulation of epidermal growth factor receptors. Clinical Cancer Research 3 1943–1948.

↵

Figlin RA, Belldegrun AS, Crawford J, Lohner M, Roskos L, Yang X-D, Foon KA, Schwab G & Weiner L 2002 ABX-EGF, a fully human anti-epidermal growth factor receptor monoclonal antibody in patients with advanced cancer:phase I clinical results. Proceedings of the American Society of Clinical Oncology 21 10a Abstract 35.

Finkler N, Gordon A, Crozier M, Edwards R, Figueroa JGA, Hainsworth J, Irwin D, Silberman S, Allen L, Ferrante K et al. 2001 Phase 2 evaluation of OSI-774, a potent oral antagonist of the EGFR-TK in patients with advanced ovarian carcinoma. Proceedings of the American Society of Clinical Oncology 20 208a Abstract 831.

↵

Fountzilas G, Pectasides D, Skarlos CV, Kalofonos HP, Papadimitriou C, Linardou H, Saridaki Z, Briasoulis E, Kosmidis P, Razis E et al. 2003 Paclitaxel, carboplatin and gefitinib (‘Iressa ’, ZD1839) as first-line chemotherapy in patients with advanced breast cancer:a phase II study. Poster presented at:26th San Antonio Breast Cancer Symposium. Poster 357.

↵

Fukuoka M, Yano S, Giaccone G, Tamura T, Nakagawa K, Douillard JY, Nishiwaki Y, Vansteenkiste J, Kudoh S, Rischin D et al. 2003 Multi-institutional randomized phase ii trial of gefitinib for previously treated patients with advanced non-small-cell lung cancer. Journal of Clinical Oncology 21 2237–2246.

↵

Gatzemeier U, Rosell R, Ramlau G, Robinet G, Szczesna A, Quoix E, Font A, Jimenez E, Mueser M & Harstrick A 2003 Cetuximab (C225) in combination with cisplatin/vinorelbine vs cisplatin/vinorelbine alone in the first-line treatment of patients with epidermal growth factor receptor (EGFR)- positive advanced non-small cell lung cancer (NSCLC). Proceedings of the American Society of Clinical Oncology 22 642 Abstract 2582.

↵

Gatzemeier U, Pluzanska A, Szczesna A, Kaukel E, Roubec J, Brennscheidt U, De Rosa F, Mueller B & von Pawel J 2004 Results of a phase III trial of erlotinib (OSI-774) combined with cisplatin and gemcitabine (GC) chemotherapy in advanced non-small cell lung cancer (NSCLC). Proceedings of the American Society of Clinical Oncology 23 617 Abstract 7010.

↵

Giaccone G, Johnson DH, Manegold C, Scagliotti GV, Rosell R, Wolf M, Rennie P, Ochs J, Averbuch S & Fandi A 2002 A phase III clinical trial of ZD1839 (‘Iressa ’) in combination with gemcitabine and cisplatin in chemotherapy-naïve patients with advanced non-small-cell lung cancer (INTACT 1). Annals of Oncology 13 2. Abstract 40.

↵

Giaccone G, Johnson D, Scagliotti GV, Manegold C, Rosell R, Rennie P, Wolf M, Averbuch S, Grous J & Fandi A 2003 Results of a multivariate analysis of prognostic factors of overall survival of patients with advanced non-small cell lung cancer treated with gefitinib (ZD1839) in combination with platinum-based chemotherapy in two large phase III trials (INTACT 1 and 2). Proceedings of the American Society of Clinical Oncology 22 627 Abstract 2522.

↵

Goldstein NI, Prewett M, Zuklys K, Rockwell P & Mendelsohn J 1995 Biological efficacy of a chimeric antibody to the epidermal growth factor receptor in a human tumor xenograft model. Clinical Cancer Research 1 1311–1318.

↵

Grant S, Qiao L & Dent P 2002 Roles of ERBB family receptor tyrosine kinases, and downstream signaling pathways, in the control of cell growth and survival. Frontiers in Bioscience 7 d376–d389.

↵

Grunwald V & Hidalgo M 2003a Developing inhibitors of the epidermal growth factor receptor for cancer treatment. Journal of the National Cancer Institute 95 851–867.

Grunwald V & Hidalgo M 2003b Development of the epidermal growth factor receptor inhibitor OSI-774. Seminars in Oncology 30 23–31.

↵

Harari PM & Huang S-M 2001 Radiation response modification following molecular inhibition of epidermal growth factor receptor signaling. Seminars in Radiation Oncology 11 281–289.

↵

Harari PM, Huang S-M, Herbst R & Quon H 2003 Molecular targeting of the epidermal growth factor receptor in head and neck cancer. In Head and Neck Cancer:a Multidisciplinary Approach , pp 1001–1016. Eds Harrison LB, Sessions RB & Hong WK. Philadelphia, PA, USA:Lippincott, Williams and Wilkins.

↵

Herbst RS 2002 Targeted therapy in non-small-cell lung cancer. Oncology 16 19–24.

↵

Herbst RS 2003a Dose-comparative monotherapy trials of ZD1839 in previously treated non-small cell lung cancer patients. Seminars in Oncology 30 30–38.

↵

Herbst RS 2003b Erlotinib (Tarceva):an update on the clinical trial program. Seminars in Oncology 30 34–46.

↵

Herbst RS & Hong WK 2002 IMC-C225, an anti-epidermal growth factor receptor monoclonal antibody for treatment of head and neck cancer. Seminars in Oncology 29 18–30.

↵

Herbst RS & Shin DM 2002 Monoclonal antibodies to target epidermal growth factor receptor-positive tumors:a new paradigm for cancer therapy. Cancer 94 1593–1611.

↵

Herbst RS, Giaccone G, Schiller J, Miller V, Natale R, Rennie P, Ochs J, Fandi A, Grous J & Johnson D 2003 Subset analyses of INTACT results for gefitinib (ZD1839) when combined with platinum-based chemotherapy for advanced non-small cell lung cancer. Proceedings of the American Society of Clinical Oncology 22 627 Abstract 2523.

↵

Herbst RS, Prager D, Hermann R, Miller V, Fehrenbacher L, Hoffman P, Johnson B, Sandler AB, Mass R & Johnson DH 2004 TRIBUTE —A phase III trial of erlotinib HCI (OSI-774) combined with carboplatin and paclitaxel (CP) chemotherapy in advanced non-small cell lung cancer (NSCLC). Proceedings of the American Society of Clinical Oncology 23 617 Abstract 7011.

↵

Hidalgo M, Siu LL, Nemunaitis J, Rizzo J, Hammond LA, Takimoto C, Eckhardt SG, Tolcher A, Britten CD, Denis L et al. 2001 Phase I and pharmacologic study of OSI-774, an epidermal growth factor receptor tyrosine kinase inhibitor, in patients with advanced solid malignancies. Journal of Clinical Oncology 19 3267–3279.

↵

Hirata A, Ogawa S, Kometani T, Kuwano T, Naito S, Kuwano M & Ono M 2002 ZD1839 (Iressa) induces antiangiogenic effects through inhibition of epidermal growth factor receptor tyrosine kinase. Cancer Research 62 2554–2560.

↵

Huang SM & Harari PM 1999 Epidermal growth factor receptor inhibition in cancer therapy: biology, rationale and preliminary clinical results. Investigational New Drugs 17 259–269.

↵

Huang SM, Bock JM & Harari PM 1999 Epidermal growth factor receptor blockade with C225 modulates proliferation, apoptosis, and radiosensitivity in squamous cell carcinomas of the head and neck. Cancer Research 59 1935–1940.

↵

Iwata KK, Provoncha K & Gibson N 2002 Inhibition of mutant EGFRvIII transformed cells by tyrosine kinase inhibitor OSI-774 (Tarceva). Proceedings of the American Society of Clinical Oncology 21 21a Abstract 79.

↵

Johnson DH, Herbst R, Giaccone G, Schiller J, Natale RB, Miller V, Wolf M, Helton A, Averbuch S & Grous J 2002 ZD1839 (‘Iressa ’) in combination with paclitaxel & carboplatin in chemotherapy-naive patients with advanced non-small-cell lung cancer (NSCLC):results from a phase III clinical trial (INTACT 2). Annals of Oncology 13 127. Abstract 4680.

Jungbluth AA, Stockert E, Huang HJS, Collins VP, Coplan K, Iversen K, Kolb D, Johns TJ, Scott AM, Gullick WJ et al. 2003 A monoclonal antibody recognizing human cancers with amplification/overexpression of the human epidermal growth factor receptor. PNAS 100 639–644.

↵

Karashima T, Sweeney P, Slaton JW, Kim SJ, Kedar D, Izawa JI, Fan Z, Pettaway C, Hicklin DJ, Shuin T et al. 2002 Inhibition of angiogenesis by the antiepidermal growth factor receptor antibody ImClone C225 in androgen-independent prostate cancer growing orthotopically in nude mice. Clinical Cancer Research 8 1253–1264.

Karp DD, Silbrman SL, Csudae R, Wirth F, Gaynes L, Posner M, Bubley G, Koon H, Bergman M, Huang M et al. 1999 Phase I dose escalation study of epidermal growth factor receptor (EGFR) tyrosine kinase (TK) inhibitor CP-358, 774 in patients with advanced solid tumors. Proceedings of the American Society of Clinical Oncology 18 388a Abstract 1499.

↵

Kelly K, Hanna N, Rosenberg A, Bunn PA & Needle MN 2003 A multicenter phase I/II study of cetuximab in combination with paclitaxel and carboplatin in untreated patients with stage IV non-small cell lung cancer. Proceedings of the American Society of Clinical Oncology 22 644 Abstract 2592.

↵

Kies MS, Arquette MA, Nabell L, Quin D, Shin D, Needle MN, Waksal H, Hong WK & Herbst RS 2002 Final report of the efficacy and safety of the anti-epidermal growth factor antibody Erbitux (IMC-C225), in combination with cisplatin in patients with recurrent squamous cell carcinoma of the head and neck (SCCHN) refractory to cisplatin containing chemotherapy. Proceedings of the American Society of Clinical Oncology 21 232a Abstract 925.

↵

Kim ES, Khuri FR & Herbst RS 2001 Epidermal growth factor receptor biology (IMC-C225). Current Opinion in Oncology 13 506–513.

↵

Kim ES, Mauer AM, Fossella FV, Jamison TA, Kies MS, Pisters KM, Glisson BS, Blumenschein GRJ, Zinner RG, Tran HT et al. 2002 A phase II study of erbitux (IMC-C225), an epidermal growth factor receptor (EGFR) blocking antibody, in combination with docetaxel in chemotherapy refractory/resistant patients with advanced non-small cell lung cancer (NSCLC). Proceedings of the American Society of Clinical Oncology 21 293a Abstract 1168.

↵

Kris MG, Natale RB, Herbst RS, Lynch TJJ, Prager D, Belani CP, Schiller JH, Kelly K, Spiridonidis C, Albain KS et al. 2002 A phase II trial of ZD1839 (‘Iressa ’) in advanced non-small cell lung cancer (NSCLC) patients who had failed platinum-and docetaxel-based regimens (IDEAL 2). Proceedings of the American Society of Clinical Oncology 21 292a. Abstract 1166.

↵

Kris MG, Natale RB, Herbst RS, Lynch TJ Jr, Prager D, Belani CP, Schiller JH, Kelly K, Spiridonidis H, Sandler A et al. 2003 Efficacy of gefitinib, an inhibitor of the epidermal growth factor receptor tyrosine kinase, in symptomatic patients with non-small cell lung cancer:a randomized trial. Journal of the American Medical Association 290 2149–2158.

↵

Lynch DH & Yang XD 2002 Therapeutic potential of ABX-EGF:a fully human anti-epidermal growth factor receptor monoclonal antibody for cancer treatment. Seminars in Oncology 29 47–50.

↵

Lynch TJ, Bell DW, Sordella R, Gurubhagavatula S, Okimoto RA, Brannigan BW, Harris PL, Haserlat SM, Supko JG, Haluska FG et al. 2004 Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. New England Journal of Medicine 350 2129–2139.

↵

Magne N, Fischel JL, Dubreuil A, Formento P, Poupon MF, Laurent-Puig P & Milano G 2002 Influence of epidermal growth factor receptor (EGFR), p53 and intrinsic MAP kinase pathway status of tumour cells on the antiproliferative effect of ZD1839 (‘Iressa ’). British Journal of Cancer 86 1518–1523.

↵

Mendelsohn J 2001 The epidermal growth factor receptor as a target for cancer therapy. Endocrine-Related Cancer 8 3–9.

↵

Mendelsohn J & Baselga J 2003 Status of epidermal growth factor receptor antagonists in the biology and treatment of cancer. Journal of Clinical Oncology 21 2787–2799.

↵

Meropol MJ, Berlin J, Hecht JR, Croghan GA, Patnaik A, Weiner LM, Sweed MF, Wiens BL, Caron D & Visonneau S 2003 Multicenter study of ABX-EFR monotherapy in patients with metastatic colorectal cancer. Proceedings of the American Society of Clinical Oncology 22 256 Abstract 1026.

↵

Miller VA, Patel J, Shah N, Kris MG, Tyson L, Pizzo B, Zakowski M, Memoli N, Sandler A & Johnson DH 2003 The epidermal growth factor receptor tyrosine kinase inhibitor erlotinib (OSI-774) shows promising activity in patients with bronchioloalveolar cell carcinoma (BAC):preliminary results of a phase II trial. Proceedings of the American Society of Clinical Oncology 22 619 Abstract 2491.

↵

Mishima K, Johns TG, Luwor RB, Scott AM, Stockert E, Jungbluth AA, Ji XD, Suvarna P, Voland JR, Old LJ et al. 2001 Growth suppression of intracranial xenografted glioblastomas overexpressing mutant epidermal growth factor receptors by systemic administration of monoclonal antibody (mAb) 806, a novel monoclonal antibody directed to the receptor. Cancer Research 61 5349–5354.

↵

Moulder SL, Yakes FM, Muthuswamy SK, Bianco R, Simpson JF & Arteaga CL 2001 Epidermal growth factor receptor (HER1) tyrosine kinase inhibitor ZD1839 (Iressa) inhibits HER2/neu (erbB2)-overexpressing breast cancer cells in vitro and in vivo. Cancer Research 61 8887–8895.

↵

Moyer JD, Barbacci EG, Iwata KK, Arnold L, Boman B, Cunningham A, DiOrio C, Doty J, Morin MJ, Moyer MP et al. 1997 Induction of apoptosis and cell cycle arrest by CP-358, 774, an inhibitor of epidermal growth factor receptor tyrosine kinase. Cancer Research 57 4838–4848.

↵

Naramura M, Gillies SD, Mendelsohn J, Reisfeld RA & Mueller BM 1993 Therapeutic potential of chimeric and murine anti-(epidermal growth factor receptor) antibodies in a metastasis model for human melanoma. Cancer Immunology and Immunotherapy 37 343–349.

↵

Needle MN 2002 Safety experience with IMC-C225, an anti-epidermal growth factor receptor antibody. Seminars in Oncology 29 55–60.

↵

Nicholson RI, Gee JM & Harper ME 2001 EGFR and cancer prognosis. European Journal of Cancer 37 (Suppl 4) S9–S15.

↵

Paez JG, Janne PA, Lee JC, Tracy S, Greulich H, Gabriel S, Herman P, Kaye FJ, Lindeman N, Boggon TJ et al. 2004 EGFR mutations in lung cancer:correlation with clinical response to gefitinib therapy. Science 304 1497–1500.

Perez-Soler R, Chachoua A, Huberman M, Karp D, Rigas J, Hammond L, Rowinsky E, Preston D, Ferrante KJ, Allen LF et al. 2001 A phase II trial of the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor OSI-774, following platinum-based chemotherapy, in patients (pts) with advanced, EGFR-expressing, non-small cell lung cancer (NSCLC). Proceedings of the American Society of Clinical Oncology 21 309a Abstract 1235.

↵

Perrotte P, Matsumoto T, Inoue K, Kuniyasu H, Eve BY, Hicklin DJ, Radinsky R & Dinney CP 1999 Anti-epidermal growth factor receptor antibody C225 inhibits angiogenesis in human transitional cell carcinoma growing orthotopically in nude mice. Clinical Cancer Research 5 257–265.

↵

Pollack VA, Savage DM, Baker DA, Tsaparikos KE, Sloan DE, Moyer JD, Barbacci EG, Pustilnik LR, Smolarek TA, Davis JA et al. 1999 Inhibition of epidermal growth factor receptor-associated tyrosine phosphorylation in human carcinomas with CP-358, 774:dynamics of receptor inhibition in situ and antitumor effects in athymic mice. Journal of Pharmacology and Experimental Therapeutics 291 739–748.

↵

Prados M, Chang S, Burton A, Kapadia A, Rabbitt J, Page M, Federoff A, Kelly S & Fyfe G 2003 Phase I study of OSI-774 alone or with temozolomide in patients with malignant glioma. Proceedings of the American Society of Clinical Oncology 22 99 Abstract 394.

↵

Prewett M, Rockwell P, Rockwell RF, Giorgio NA, Mendelsohn J, Scher HI & Goldstein NI 1996 The biologic effects of C225, a chimeric monoclonal antibody to the EGFR, on human prostate carcinoma. Journal of Immunotherapy with Emphasis on Tumor Immunology 19 419–427.

↵

Prewett M, Rothman M, Waksal H, Feldman M, Bander NH & Hicklin DJ 1998 Mouse-human chimeric anti-epidermal growth factor receptor antibody C225 inhibits the growth of human renal cell carcinoma xenografts in nude mice. Clinical Cancer Research 4 2957–2966.

↵

Prewett M, Overholser J, Hooper A & Waksal HH 1999 Growth inhibition of human pancreatic carcinoma in vitro and in vivo by chimeric anti-EGF receptor monoclonal antibody C225. Proceedings of the American Association for Cancer Research 40 730 Abstract 4818.

↵

Qu CK 2002 Role of the SHP-2 tyrosine phosphatase in cytokine-induced signaling and cellular response. Biochimica et Biophysica Acta 1592 297–301.

↵

Ranson M, Hammond LA, Ferry D, Kris M, Tullo A, Murray PI, Miller V, Averbuch S, Ochs J, Morris C et al. 2002 ZD1839, a selective oral epidermal growth factor receptor-tyrosine kinase inhibitor, is well tolerated and active in patients with solid, malignant tumors:results of a phase I trial. Journal of Clinical Oncology 20 2240–2250.

↵

Robert F, Ezekiel MP, Spencer SA, Meredith RF, Bonner JA, Khazaeli MB, Saleh MN, Carey D, LoBuglio AF, Wheeler RH et al. 2001 Phase I study of anti-epidermal growth factor receptor antibody cetuximab in combination with radiation therapy in patients with advanced head and neck cancer. Journal of Clinical Oncology 19 3234–3243.

↵

Robert F, Blumenschein G, Dicke K, Tseng J, Saleh MN & Needle M 2003 Phase IB/IIA study of anti-epidermal growth factor receptor antibody, cetuximab, in combination with gemcitabine/carboplatin in patients with advanced stage IV non-small cell lung cancer. Proceedings of the American Society of Clinical Oncology 22 643 Abstract 2587.

↵

Robertson JFR, Gutteridge E, Cheung KL, Owers R, Koehler M, Hamilton L, Gee J, Nicholson RI 2003 Gefitinib (‘Iressa ’, ZD1839) is active in acquired tamoxifen (TAM)-resistant oestrogen receptor (ER)-positive and ER-negative breast cancer:results from a phase II study. Proceedings of the American Society of Clinical Oncology 22 7 Abstract 23.

↵

Rosenberg AH, Loehrer PJ, Needle MN, Waksal H, Hollywood E, Ramos L & Saltz LB 2002 Erbitux (IMC-C225) plus weekly irinotecan (CPT-11), fluorouracil (5FU) and leucovorin (LV) in colorectal cancer (CRC) that expresses the epidermal growth factor receptor (EGFR). Proceedings of the American Society of Clinical Oncology 21 135a Abstract 536.

↵

Roskos L, Lohner M, Osborn K, Pasumarthi R, Lu H, Funelas C, Raie N, Yang X-D, Weiner L, Figlin RA et al. 2002 Low pharmacokinetic variability facilitates optimal dosing of ABX-EGF in cancer patients. Proceedings of the American Society of Clinical Oncology 21 91a Abstract 362.

↵

Salomon DS, Brandt R, Ciardiello F & Normanno N 1995 Epidermal growth factor-related peptides and their receptors in human malignancies. Critical Reviews in Oncology/Hematology 19 183–232.

↵

Saltz L, Rubin M, Hochster H, Tchekmeydian NS, Waksal H, Needle M & LoBuglio A 2001 Cetuximab (IMC-C225) plus irinotecan (CPT-11) is active in CPT-11-refractory colorectal cancer (CRC) that expresses epidermal growth factor receptor (EGFR). Proceedings of the American Society of Clinical Oncology 20 3a Abstract 7.

Saltz L, Meropol NJ, Loehrer PJ, Waksal H, Needle MN & Mayer RJ 2002 Single agent IMC-C225 (Erbitux(tm)) has activity in CPT-11-refractory colorectal cancer (CRC) that expresses the epidermal growth factor receptor (EGFR). Proceedings of the American Society of Clinical Oncology 21 127a Abstract 504.

↵

Saltz L, Kies M, Abbruzzese JL, Azarnia N & Needle M 2003 The presence and intensity of the cetuximab-induced acne-like rash predicts increased survival in studies across multiple malignancies. Proceedings of the American Society of Clinical Oncology 22 204 Abstract 817.

↵

Saul H 2003 27th ESMO Congress, Nice, 18–22 October 2002. Iressa disappoints in NSCLC. European Journal of Cancer 39 1.

↵

Schoffski P, Lutz MP, Folprecht G, Beutel G, Seufferlein T, Marschner JP, Harstrick A & Kohne CH 2002 Cetuximab (C225) plus irinotecan (CPT-11) plus infusional 5FU-folinic acid (FA) is safe and active in metastatic colorectal cancer (MCRC), that expresses epidermal growth factor receptor (EGFR). Proceedings of the American Society of Clinical Oncology 21 159a Abstract 633.

↵

Schultz J 2003 Apparent adverse drug reactions prompt concern about Iressa. Journal of the National Cancer Institute 95 577–579.

↵

Schwartz G, Dutcher J, Vogelzang N, Gollob J, Thompson J, Bukowski RM, Figlin RA, Lohner M, Roskos L, Hwang CC et al. 2002 Phase 2 clinical trial evaluating the safety and effectiveness of ABX-EGF in renal cell cancer (RCC). Proceedings of the American Society of Clinical Oncology 21 Abstract 91.

↵

Shepherd FA, Pereira J, Ciuleanu TE, Tan EH, Hirsh V, Thongprasert S, Bezjak A, Tu D, Santabarbara P & Seymour L 2004 A randomized placebo-controlled trial of erlotinib in patients with advanced non-small cell lung cancer (NSCLC) following failure of 1st line or 2nd line chemotherapy. A National Cancer Institute of Canada Clinical Trials Group (NCIC CTG) trial. Proceedings of the American Society of Clinical Oncology 23 . Abstract 7022.

↵

Shin DM, Donato NJ, Perez-Soler R, Shin HJ, Wu JY, Zhang P, Lawhorn K, Khuri FR, Glisson BS, Myers J et al. 2001 Epidermal growth factor receptor-targeted therapy with C225 and cisplatin in patients with head and neck cancer. Clinical Cancer Research 7 1204–1213.

↵

Sirotnak FM 2003 Studies with ZD1839 in preclinical models. Seminars in Oncology 30 12–20.

↵

Sirotnak FM, Zakowski MF, Miller VA, Scher HI & Kris MG 2000 Efficacy of cytotoxic agents against human tumor xenografts is markedly enhanced by coadministration of ZD1839 (Iressa), an inhibitor of EGFR tyrosine kinase. Clinical Cancer Research 6 4885–4892.

↵

Sorkina T, Huang F, Beguinot L & Sorkin A 2002 Effect of tyrosine kinase inhibitors on clathrin-coated pit recruitment and internalization of epidermal growth factor receptor. Journal of Biological Chemistry 277 27433–27441.

↵

Soulieres D, Senzer NN, Vokes EE, Hidalgo M, Agarwala SS & Siu LL 2004 Multicenter phase II study of erlotinib, an oral epidermal growth factor receptor tyrosine kinase inhibitor, in patients with recurrent or metastatic squamous cell cancer of the head and neck. Journal of Clinical Oncology 22 77–85.

↵

Toyoda H, Komurasaki T, Uchida D & Morimoto S 1997 Distribution of mRNA for human epiregulin, a differentially expressed member of the epidermal growth factor family. Biochemical Journal 326 69–75.

↵

Van Laethem J-L, Raoul J-L, Mitry E, Brezault C, Husseini F, Cals L, Vedovato JC, Mueser MM & Rougier P 2003 Cetuximab (C225) in combination with bi-weekly irinotecan (CPT-11), infusional 5-fluorouracil (5-FU), and folinic acid (FA) in patients with metastatic colorectal cancer (CRC) expressing the epidermal growth factor receptor (EGFR). Preliminary safety and efficacy results. Proceedings of the American Society of Clinical Oncology 22 264 Abstract 1058.

↵

Vega-Villegas E, Awada R, Mesia L Geoffrois L, Borel C, Humblet Y, Lopez-Poussa A, Hitt R, Amellal N & Bourhis J 2003 A phase I study of cetuximab in combination with cisplatin or carboplatin and 5-FU in patients with recurrent or metastatic squamous cell carcinoma of the head and neck. Proceedings of the American Association for Cancer Research 22 502 Abstract 2020.

↵

Viens P, L ’Homme C, Extra JM, Gladieff L, Kalla S & Fabbro M 2003 A phase II trial to evaluate efficacy and safety of gefitinib (ZD1836) in patients with loco-regionally advanced or metastatic squamous cell carcinoma of the cervix. Proceedings of the American Society of Clinical Oncology 22 456 Abstract 1833.

↵

Viloria-Petit AM, Rak J, Hung MC, Rockwell P, Goldstein N, Fendly B & Kerbel RS 1997 Neutralizing antibodies against epidermal growth factor and ErbB-2/neu receptor tyrosine kinases down-regulate vascular endothelial growth factor production by tumor cells in vitro and in vivo:angiogenic implications for signal transduction therapy of solid tumors. American Journal of Pathology 151 1523–1530.

Wang P, Fredlin P, Davis CG & Yang X-D 2002 Therapeutic potential of ABX-EGF, a fully human anti-EGF receptor monoclonal antibody for the treatment of renal cell carcinoma. Proceedings of the American Society of Clinical Oncology 21 191a Abstract 761.

↵

Wang P, Fredlin P, Davis CG & Yang X-D 2003 Human anti-EGF receptor monoclonal antibody ABX-EGF:a potential monotherapy for the treatment of prostate cancer. Proceedings of the American Society of Clinical Oncology 22. Abstract 4525.

↵

Watanabe T, Shintani A, Nakata M, Shing Y, Folkman J, Igarashi K & Sasada R 1994 Recombinant human betacellulin. Molecular structure, biological activities, and receptor interaction. Journal of Biological Chemistry 269 9966–9973.

↵

Wells A 1999 EGF receptor. International Journal of Biochemistry and Cell Biology 31 637–643.

↵

Wiley HS 2003 Trafficking of the ErbB receptors and its influence on signaling. Experimental Cell Research 284 78–88.

↵

Woodburn JR 1999 The epidermal growth factor receptor and its inhibition in cancer therapy. Pharmacology and Therapeutics 82 241–250.

↵

Woodburn JR, Kendrew J, Fennell M & Wakeling AE 2000 ZD1839 (‘IRESSA ’) A selective epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI):inhibition of c-fos mRNA, an intermediate marker of EGFR activation, correlates with tumor growth inhibition. Proceedings of the American Association for Cancer Research 41 402 Abstract 2552.

↵

Yang XD, Jia XC, Corvalan JR, Wang P, Davis CG & Jakobovits A 1999 Eradication of established tumors by a fully human monoclonal antibody to the epidermal growth factor receptor without concomitant chemotherapy. Cancer Research 59 1236–1243.

↵

Yang XD, Jia XC, Corvalan JR, Wang P & Davis CG 2001 Development of ABX-EGF, a fully human anti-EGF receptor monoclonal antibody, for cancer therapy. Critical Reviews in Oncology/Hematology 38 17–23.

↵

Yarden Y 2001 The EGFR family and its ligands in human cancer:signalling mechanisms and therapeutic opportunities. European Journal of Cancer 37 (Suppl 4) S3–S8.

↵

Yarden Y & Sliwkowski MX 2001 Untangling the ErbB signalling network. Nature Reviews. Molecular Cell Biology 2 127–137.

[1] ↵

Aaronson SA 1991 Growth factors and cancer. Science 254 1146–1153.

[2] ↵

Abbruzzese JL, Rosenberg A, Xiong Q, LoBuglio A, Schmidt W, Wolff R, Needle M & Waksal H 2001 Phase II study of antiepidermal growth factor receptor (EGFR) antibody cetuximab (IMC-C225) in combination with gemcitabine in patients with advanced pancreatic cancer. Proceedings of the American Society of Clinical Oncology 20 130a. Abstract 518.

[3] ↵

Akita RW & Sliwkowski MX 2003 Preclinical studies with Erlotinib (Tarceva). Seminars in Oncology 30 15–24.

[4] ↵

Albanell J, Rojo F & Baselga J 2001 Pharmacodynamic studies with the epidermal growth factor receptor tyrosine kinase inhibitor ZD1839. Seminars in Oncology 28 56–66.

[5] ↵

Alroy I & Yarden Y 1997 The ErbB signaling network in embryogenesis and oncogenesis:signal diversification through combinatorial ligand–receptor interactions. FEBS Letters 410 83–86.

[6] ↵

Arteaga CL 2002 Epidermal growth factor receptor dependence in human tumors: more than just expression? Oncologist 7 (Suppl 4) 31–39.

[7] ↵

Arteaga CL & Baselga J 2003 Clinical trial design and end points for epidermal growth factor receptor-targeted therapies: implications for drug development and practice. Clinical Cancer Research 9 1579–1589.

[8] ↵

Arteaga CL & Johnson DH 2001 Tyrosine kinase inhibitors-ZD1839 (Iressa). Current Opinion in Oncology 13 491–498.

[9] ↵

AstraZeneca Pharmaceuticals LP 2003 Iressa (gefitinib) product label.

[10] ↵

Barnes CJ, Bagheri-Yarmand R, Mandal M, Yang Z, Clayman GL, Hong WK & Kumar R 2003 Suppression of epidermal growth factor receptor, mitogen-activated protein kinase, and Pak1 pathways and invasiveness of human cutaneous squamous cancer cells by the tyrosine kinase inhibitor ZD1839 (Iressa). Molecular Cancer Therapeutics 2 345–351.

[11] ↵

Baselga J 2001 The EGFR as a target for anticancer therapy — focus on cetuximab. European Journal of Cancer 37 (Suppl 4) S16–S22.

[12] ↵

Baselga J & Averbuch SD 2000 ZD1839 (‘Iressa ’) as an anticancer agent. Drugs 60 (Suppl 1) 33–40.

[13] ↵

Baselga J, Pfister D, Cooper MR, Cohen R, Burtness B, Bos M, D ’Andrea G, Seidman A, Norton L, Gunnett K, Falcey J, Anderson V, Waksal H & Mendelsohn J 2000 Phase I studies of anti-epidermal growth factor receptor chimeric antibody C225 alone and in combination with cisplatin. Journal of Clinical Oncology 18 904–914.

[14] ↵

Baselga J, Trigo JM, Bourhis J, Tortochaux J, Cortes-Funes H, Hitt R, Gascon P, Muesser M, Harstrick A & Eckardt A 2002 Cetuximab (C225) plus cisplatin/carboplatin is active in patients (pts) with recurrent/metastatic squamous cell carcinoma of the head and neck (SCCHN) progressing on a same dose and schedule platinum-based regimen. Proceedings of the American Society of Clinical Oncology 21 226a. Abstract 900.

[15] ↵

Baselga J, Albanell J, Ruiz A, Lluch A, Gascon P, Gonzalez S, Guillen V, Sauleda S, Averbuch S & Rojo F 2003 Phase II and tumor pharmacodynamic study of gefitinib (ZD1839) in patients with advanced breast cancer. Proceedings of the American Society of Clinical Oncology 22 7 Abstract 24.

[16] ↵

Bishop PC, Myers T, Robey R, Fry DW, Liu ET, Blagosklonny MV & Bates SE 2002 Differential sensitivity of cancer cells to inhibitors of the epidermal growth factor receptor family. Oncogene 21 119–127.

[17] ↵

Bonner JA, Giralt J, Harari PM, Cohen R, Jones C, Sur RK, Rabin D, Azarnia N, Needle MN & Ang KK 2004 Cetuximab prolongs survival in patients with locoregionally advanced squamous cell carcinoma of head and neck:a phase III study of high dose radiation therapy with or without cetuximab. Proceedings of the American Society of Clinical Oncology 23 Abstract 5507.

[18] ↵

Burtness BA, Li Y, Flood W, Mattar BI & Forastiere AA 2002 Phase III trial comparing cisplatin (C) + placebo (P) to C + anti-epidermal growth factor antibody (EGF-R) C225 in patients (PTS) with metastatic/recurrent head and neck cancer (HNC). Proceedings of the American Society of Clinical Oncology 21 901 Abstract.

[19] ↵

Busam KJ, Capodieci P, Motzer R, Kiehn T, Phelan D & Halpern AC 2001 Cutaneous side-effects in cancer patients treated with the antiepidermal growth factor receptor antibody C225. British Journal of Dermatology 144 1169–1176.

[20] ↵

Carpenter G 2000 The EGF receptor:a nexus for trafficking and signaling. Bioessays 22 697–707.

[21] ↵

Carpenter G & Cohen S 1990 Epidermal growth factor. Journal of Biological Chemistry 265 7709–7712.

[22] ↵

Cella D 2003 Impact of ZD1839 on non-small cell lung cancer-related symptoms as measured by the functional assessment of cancer therapy-lung scale. Seminars in Oncology 30 39–48.

[23] ↵

Chan ATC, Hsu MM, Goh BC, Hui EP, Liu TW, Millward M, Chang AY, Ma BB, Hong RL, Lin X et al. 2003 A phase II study of cetuximab (C225) in combination with carboplatin in patients with recurrent or metastatic nasopharyngeal carcinoma who failed on platinum-based chemotherapy. Proceedings of the American Society of Clinical Oncology 22 497 Abstract 2000.

[24] ↵

Cho CD, Fisher GA, Halsey J, Jambalos CN, Advani RH, Wakelee H, Lum BL & Sikic BI 2003 A phase II study of gefitinib in combination with FOLFOX-4 (IFOX) in patients with unresectable or metastatic colorectal cancer. Proceedings of the American Society of Clinical Oncology 22 265 Abstract 1062.

[25] ↵

Ciardiello F 2000 Epidermal growth factor receptor tyrosine kinase inhibitors as anticancer agents. Drugs 60 (Suppl 1) 25–32.

[26] ↵

Ciardiello F, Caputo R, Bianco R, Damiano V, Pomatico G, De Placido S, Bianco AR & Tortora G 2000 Antitumor effect and potentiation of cytotoxic drugs activity in human cancer cells by ZD-1839 (Iressa), an epidermal growth factor receptor-selective tyrosine kinase inhibitor. Clinical Cancer Research 6 2053–2063.

[27] ↵

Cohen EE, Rosen F, Dekker A, Bajda C, Stenson K, Shulman KL, Lamont E, Kozloff M & Vokes EE 2002 Phase II study of ZD1839 (Iressa) in recurrent of metastatic squamous cell carcinoma of the head and neck (SCCHN). Proceedings of the American Society of Clinical Oncology 21 225a Abstract 899.

[28] ↵

Cohen EE, Rosen F, Stadler WM, Recant W, Stenson K, Huo D & Vokes EE 2003a Phase II trial of ZD1839 in recurrent or metastatic squamous cell carcinoma of the head and neck. Journal of Clinical Oncology 21 1980–1987.

[29] ↵

Cohen EE, Stenson K, Gustin DM, Lamont E, Mauer AM, Blair E, Stadler WM, Dekker A, Mallon W & Vokes EE 2003b A phase II study of 250 mg gefitinib (ZD1839) monotherapy in recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN). Proceedings of the American Society of Clinical Oncology 22 502 Abstract 2021.

[30] ↵

Cohen RB 2003 Epidermal growth factor receptor as a therapeutic target in colorectal cancer. Clinical Colorectal Cancer 2 246–251.

[31] ↵

Cunningham D, Humblet Y, Siena S, Khayat D, Bleiberg H, Santoro A, Bets D, Mueser M, Harstrick A & Van Cutsem E 2003 Cetuximab (C225) alone or in combination with irinotecan (CPT-11) in patients with epidermal growth factor receptor (EGFR)-positive, irinotecan-refractory metastatic colorectal cancer. Proceedings of the American Society of Clinical Oncology 22 252 Abstract 1012.

[32] ↵

Dancey JE & Freidlin B 2003 Targeting epidermal growth factor receptor —are we missing the mark? Lancet 362 62–64.

[33] ↵

Davis CG, Gallo ML & Corvalan JR 1999 Transgenic mice as a source of fully human antibodies for the treatment of cancer. Cancer Metastasis Reviews 18 421–425.

[34] ↵

Dawson NA, Guo C, Zak R, Dorsey B, Smoot J, Wong J & Hussain A 2003 A phase II trial of ZD1839 in stage IV and recurrent renal cell carcinoma. Proceedings of the American Society of Clinical Oncology 22 404 Abstract 1623.

[35] ↵

Di Gennaro E, Barbarino M, Bruzzese F, De Lorenzo S, Caraglia M, Abbruzzese A, Avallone A, Comella P, Caponigro F, Pepe S et al. 2003 Critical role of both p27KIP1 and p21CIP1/WAF1 in the antiproliferative effect of ZD1839 (‘Iressa ’), an epidermal growth factor receptor tyrosine kinase inhibitor, in head and neck squamous carcinoma cells. Journal of Cellular Physiology 195 139–150.

[36] ↵

Douillard J-Y, Giaccone G, Horai T, Noda K, Vansteenkiste JF, Takata I, Gatzemeier U, Fukuoka M, Macleod A, Feyereislova A et al. 2002 Improvement in disease-related symptoms and quality of life in patients with advanced non-small-cell lung cancer (NSCLC) treated with ZD1839 (‘Iressa ’) (IDEAL 1). Proceedings of the American Society of Clinical Oncology 21 299a. Abstract 1195.

[37] ↵

Dragovich T, Patnaik A, Rowinsky EK, Karp D, Huberman M, Clinebell T, Hamilton M, Zitelli A, Nadler P & Wood DL 2003 A phase I B trial of gemcitabine and erlotinib HCl in patients with advanced pancreatic adenocarcinoma and other potentially responsive malignancies. Proceedings of the American Society of Clinical Oncology 22 223 Abstract 895.

[38] ↵

Drucker BJ, Schwartz L, Marion S & Motzer R 2002 Phase II trial of ZD1839 (Iressa), an EGF receptor inhibitor, in patients with advanced renal cell carcinoma. Proceedings of the American Society of Clinical Oncology 21 181a Abstract 720.

[39] ↵

Earp HSIII, Calvo BF & Sartor CI 2003 The EGF receptor family–multiple roles in proliferation, differentiation, and neoplasia with an emphasis on HER4. Transactions of the American Clinical and Climatological Association 114 315–333.

[40] ↵

Ennis BW, Lippman ME & Dickson RB 1991 The EGF receptor system as a target for antitumor therapy. Cancer Investigation 9 553–562.

[41] ↵

Fan Z, Shang BY, Lu Y, Chou JL & Mendelsohn J 1997 Reciprocal changes in p27(Kip1) and p21(Cip1) in growth inhibition mediated by blockade or overstimulation of epidermal growth factor receptors. Clinical Cancer Research 3 1943–1948.

[42] ↵

Figlin RA, Belldegrun AS, Crawford J, Lohner M, Roskos L, Yang X-D, Foon KA, Schwab G & Weiner L 2002 ABX-EGF, a fully human anti-epidermal growth factor receptor monoclonal antibody in patients with advanced cancer:phase I clinical results. Proceedings of the American Society of Clinical Oncology 21 10a Abstract 35.

[43] Finkler N, Gordon A, Crozier M, Edwards R, Figueroa JGA, Hainsworth J, Irwin D, Silberman S, Allen L, Ferrante K et al. 2001 Phase 2 evaluation of OSI-774, a potent oral antagonist of the EGFR-TK in patients with advanced ovarian carcinoma. Proceedings of the American Society of Clinical Oncology 20 208a Abstract 831.

[44] ↵

Fountzilas G, Pectasides D, Skarlos CV, Kalofonos HP, Papadimitriou C, Linardou H, Saridaki Z, Briasoulis E, Kosmidis P, Razis E et al. 2003 Paclitaxel, carboplatin and gefitinib (‘Iressa ’, ZD1839) as first-line chemotherapy in patients with advanced breast cancer:a phase II study. Poster presented at:26th San Antonio Breast Cancer Symposium. Poster 357.

[45] ↵

Fukuoka M, Yano S, Giaccone G, Tamura T, Nakagawa K, Douillard JY, Nishiwaki Y, Vansteenkiste J, Kudoh S, Rischin D et al. 2003 Multi-institutional randomized phase ii trial of gefitinib for previously treated patients with advanced non-small-cell lung cancer. Journal of Clinical Oncology 21 2237–2246.

[46] ↵

Gatzemeier U, Rosell R, Ramlau G, Robinet G, Szczesna A, Quoix E, Font A, Jimenez E, Mueser M & Harstrick A 2003 Cetuximab (C225) in combination with cisplatin/vinorelbine vs cisplatin/vinorelbine alone in the first-line treatment of patients with epidermal growth factor receptor (EGFR)- positive advanced non-small cell lung cancer (NSCLC). Proceedings of the American Society of Clinical Oncology 22 642 Abstract 2582.

[47] ↵

Gatzemeier U, Pluzanska A, Szczesna A, Kaukel E, Roubec J, Brennscheidt U, De Rosa F, Mueller B & von Pawel J 2004 Results of a phase III trial of erlotinib (OSI-774) combined with cisplatin and gemcitabine (GC) chemotherapy in advanced non-small cell lung cancer (NSCLC). Proceedings of the American Society of Clinical Oncology 23 617 Abstract 7010.

[48] ↵

Giaccone G, Johnson DH, Manegold C, Scagliotti GV, Rosell R, Wolf M, Rennie P, Ochs J, Averbuch S & Fandi A 2002 A phase III clinical trial of ZD1839 (‘Iressa ’) in combination with gemcitabine and cisplatin in chemotherapy-naïve patients with advanced non-small-cell lung cancer (INTACT 1). Annals of Oncology 13 2. Abstract 40.

[49] ↵

Giaccone G, Johnson D, Scagliotti GV, Manegold C, Rosell R, Rennie P, Wolf M, Averbuch S, Grous J & Fandi A 2003 Results of a multivariate analysis of prognostic factors of overall survival of patients with advanced non-small cell lung cancer treated with gefitinib (ZD1839) in combination with platinum-based chemotherapy in two large phase III trials (INTACT 1 and 2). Proceedings of the American Society of Clinical Oncology 22 627 Abstract 2522.

[50] ↵

Goldstein NI, Prewett M, Zuklys K, Rockwell P & Mendelsohn J 1995 Biological efficacy of a chimeric antibody to the epidermal growth factor receptor in a human tumor xenograft model. Clinical Cancer Research 1 1311–1318.

[51] ↵

Grant S, Qiao L & Dent P 2002 Roles of ERBB family receptor tyrosine kinases, and downstream signaling pathways, in the control of cell growth and survival. Frontiers in Bioscience 7 d376–d389.

[52] ↵

Grunwald V & Hidalgo M 2003a Developing inhibitors of the epidermal growth factor receptor for cancer treatment. Journal of the National Cancer Institute 95 851–867.

[53] Grunwald V & Hidalgo M 2003b Development of the epidermal growth factor receptor inhibitor OSI-774. Seminars in Oncology 30 23–31.

[54] ↵

Harari PM & Huang S-M 2001 Radiation response modification following molecular inhibition of epidermal growth factor receptor signaling. Seminars in Radiation Oncology 11 281–289.

[55] ↵

Harari PM, Huang S-M, Herbst R & Quon H 2003 Molecular targeting of the epidermal growth factor receptor in head and neck cancer. In Head and Neck Cancer:a Multidisciplinary Approach , pp 1001–1016. Eds Harrison LB, Sessions RB & Hong WK. Philadelphia, PA, USA:Lippincott, Williams and Wilkins.

[56] ↵

Herbst RS 2002 Targeted therapy in non-small-cell lung cancer. Oncology 16 19–24.

[57] ↵

Herbst RS 2003a Dose-comparative monotherapy trials of ZD1839 in previously treated non-small cell lung cancer patients. Seminars in Oncology 30 30–38.

[58] ↵

Herbst RS 2003b Erlotinib (Tarceva):an update on the clinical trial program. Seminars in Oncology 30 34–46.

[59] ↵

Herbst RS & Hong WK 2002 IMC-C225, an anti-epidermal growth factor receptor monoclonal antibody for treatment of head and neck cancer. Seminars in Oncology 29 18–30.

[60] ↵

Herbst RS & Shin DM 2002 Monoclonal antibodies to target epidermal growth factor receptor-positive tumors:a new paradigm for cancer therapy. Cancer 94 1593–1611.

[61] ↵

Herbst RS, Giaccone G, Schiller J, Miller V, Natale R, Rennie P, Ochs J, Fandi A, Grous J & Johnson D 2003 Subset analyses of INTACT results for gefitinib (ZD1839) when combined with platinum-based chemotherapy for advanced non-small cell lung cancer. Proceedings of the American Society of Clinical Oncology 22 627 Abstract 2523.

[62] ↵

Herbst RS, Prager D, Hermann R, Miller V, Fehrenbacher L, Hoffman P, Johnson B, Sandler AB, Mass R & Johnson DH 2004 TRIBUTE —A phase III trial of erlotinib HCI (OSI-774) combined with carboplatin and paclitaxel (CP) chemotherapy in advanced non-small cell lung cancer (NSCLC). Proceedings of the American Society of Clinical Oncology 23 617 Abstract 7011.

[63] ↵

Hidalgo M, Siu LL, Nemunaitis J, Rizzo J, Hammond LA, Takimoto C, Eckhardt SG, Tolcher A, Britten CD, Denis L et al. 2001 Phase I and pharmacologic study of OSI-774, an epidermal growth factor receptor tyrosine kinase inhibitor, in patients with advanced solid malignancies. Journal of Clinical Oncology 19 3267–3279.

[64] ↵

Hirata A, Ogawa S, Kometani T, Kuwano T, Naito S, Kuwano M & Ono M 2002 ZD1839 (Iressa) induces antiangiogenic effects through inhibition of epidermal growth factor receptor tyrosine kinase. Cancer Research 62 2554–2560.

[65] ↵

Huang SM & Harari PM 1999 Epidermal growth factor receptor inhibition in cancer therapy: biology, rationale and preliminary clinical results. Investigational New Drugs 17 259–269.

[66] ↵

Huang SM, Bock JM & Harari PM 1999 Epidermal growth factor receptor blockade with C225 modulates proliferation, apoptosis, and radiosensitivity in squamous cell carcinomas of the head and neck. Cancer Research 59 1935–1940.

[67] ↵

Iwata KK, Provoncha K & Gibson N 2002 Inhibition of mutant EGFRvIII transformed cells by tyrosine kinase inhibitor OSI-774 (Tarceva). Proceedings of the American Society of Clinical Oncology 21 21a Abstract 79.

[68] ↵

Johnson DH, Herbst R, Giaccone G, Schiller J, Natale RB, Miller V, Wolf M, Helton A, Averbuch S & Grous J 2002 ZD1839 (‘Iressa ’) in combination with paclitaxel & carboplatin in chemotherapy-naive patients with advanced non-small-cell lung cancer (NSCLC):results from a phase III clinical trial (INTACT 2). Annals of Oncology 13 127. Abstract 4680.

[69] Jungbluth AA, Stockert E, Huang HJS, Collins VP, Coplan K, Iversen K, Kolb D, Johns TJ, Scott AM, Gullick WJ et al. 2003 A monoclonal antibody recognizing human cancers with amplification/overexpression of the human epidermal growth factor receptor. PNAS 100 639–644.

[70] ↵

Karashima T, Sweeney P, Slaton JW, Kim SJ, Kedar D, Izawa JI, Fan Z, Pettaway C, Hicklin DJ, Shuin T et al. 2002 Inhibition of angiogenesis by the antiepidermal growth factor receptor antibody ImClone C225 in androgen-independent prostate cancer growing orthotopically in nude mice. Clinical Cancer Research 8 1253–1264.

[71] Karp DD, Silbrman SL, Csudae R, Wirth F, Gaynes L, Posner M, Bubley G, Koon H, Bergman M, Huang M et al. 1999 Phase I dose escalation study of epidermal growth factor receptor (EGFR) tyrosine kinase (TK) inhibitor CP-358, 774 in patients with advanced solid tumors. Proceedings of the American Society of Clinical Oncology 18 388a Abstract 1499.

[72] ↵

Kelly K, Hanna N, Rosenberg A, Bunn PA & Needle MN 2003 A multicenter phase I/II study of cetuximab in combination with paclitaxel and carboplatin in untreated patients with stage IV non-small cell lung cancer. Proceedings of the American Society of Clinical Oncology 22 644 Abstract 2592.

[73] ↵

Kies MS, Arquette MA, Nabell L, Quin D, Shin D, Needle MN, Waksal H, Hong WK & Herbst RS 2002 Final report of the efficacy and safety of the anti-epidermal growth factor antibody Erbitux (IMC-C225), in combination with cisplatin in patients with recurrent squamous cell carcinoma of the head and neck (SCCHN) refractory to cisplatin containing chemotherapy. Proceedings of the American Society of Clinical Oncology 21 232a Abstract 925.

[74] ↵

Kim ES, Khuri FR & Herbst RS 2001 Epidermal growth factor receptor biology (IMC-C225). Current Opinion in Oncology 13 506–513.

[75] ↵

Kim ES, Mauer AM, Fossella FV, Jamison TA, Kies MS, Pisters KM, Glisson BS, Blumenschein GRJ, Zinner RG, Tran HT et al. 2002 A phase II study of erbitux (IMC-C225), an epidermal growth factor receptor (EGFR) blocking antibody, in combination with docetaxel in chemotherapy refractory/resistant patients with advanced non-small cell lung cancer (NSCLC). Proceedings of the American Society of Clinical Oncology 21 293a Abstract 1168.

[76] ↵

Kris MG, Natale RB, Herbst RS, Lynch TJJ, Prager D, Belani CP, Schiller JH, Kelly K, Spiridonidis C, Albain KS et al. 2002 A phase II trial of ZD1839 (‘Iressa ’) in advanced non-small cell lung cancer (NSCLC) patients who had failed platinum-and docetaxel-based regimens (IDEAL 2). Proceedings of the American Society of Clinical Oncology 21 292a. Abstract 1166.

[77] ↵

Kris MG, Natale RB, Herbst RS, Lynch TJ Jr, Prager D, Belani CP, Schiller JH, Kelly K, Spiridonidis H, Sandler A et al. 2003 Efficacy of gefitinib, an inhibitor of the epidermal growth factor receptor tyrosine kinase, in symptomatic patients with non-small cell lung cancer:a randomized trial. Journal of the American Medical Association 290 2149–2158.

[78] ↵

Lynch DH & Yang XD 2002 Therapeutic potential of ABX-EGF:a fully human anti-epidermal growth factor receptor monoclonal antibody for cancer treatment. Seminars in Oncology 29 47–50.

[79] ↵

Lynch TJ, Bell DW, Sordella R, Gurubhagavatula S, Okimoto RA, Brannigan BW, Harris PL, Haserlat SM, Supko JG, Haluska FG et al. 2004 Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. New England Journal of Medicine 350 2129–2139.

[80] ↵

Magne N, Fischel JL, Dubreuil A, Formento P, Poupon MF, Laurent-Puig P & Milano G 2002 Influence of epidermal growth factor receptor (EGFR), p53 and intrinsic MAP kinase pathway status of tumour cells on the antiproliferative effect of ZD1839 (‘Iressa ’). British Journal of Cancer 86 1518–1523.

[81] ↵

Mendelsohn J 2001 The epidermal growth factor receptor as a target for cancer therapy. Endocrine-Related Cancer 8 3–9.

[82] ↵

Mendelsohn J & Baselga J 2003 Status of epidermal growth factor receptor antagonists in the biology and treatment of cancer. Journal of Clinical Oncology 21 2787–2799.

[83] ↵

Meropol MJ, Berlin J, Hecht JR, Croghan GA, Patnaik A, Weiner LM, Sweed MF, Wiens BL, Caron D & Visonneau S 2003 Multicenter study of ABX-EFR monotherapy in patients with metastatic colorectal cancer. Proceedings of the American Society of Clinical Oncology 22 256 Abstract 1026.

[84] ↵

Miller VA, Patel J, Shah N, Kris MG, Tyson L, Pizzo B, Zakowski M, Memoli N, Sandler A & Johnson DH 2003 The epidermal growth factor receptor tyrosine kinase inhibitor erlotinib (OSI-774) shows promising activity in patients with bronchioloalveolar cell carcinoma (BAC):preliminary results of a phase II trial. Proceedings of the American Society of Clinical Oncology 22 619 Abstract 2491.

[85] ↵

Mishima K, Johns TG, Luwor RB, Scott AM, Stockert E, Jungbluth AA, Ji XD, Suvarna P, Voland JR, Old LJ et al. 2001 Growth suppression of intracranial xenografted glioblastomas overexpressing mutant epidermal growth factor receptors by systemic administration of monoclonal antibody (mAb) 806, a novel monoclonal antibody directed to the receptor. Cancer Research 61 5349–5354.

[86] ↵

Moulder SL, Yakes FM, Muthuswamy SK, Bianco R, Simpson JF & Arteaga CL 2001 Epidermal growth factor receptor (HER1) tyrosine kinase inhibitor ZD1839 (Iressa) inhibits HER2/neu (erbB2)-overexpressing breast cancer cells in vitro and in vivo. Cancer Research 61 8887–8895.

[87] ↵

Moyer JD, Barbacci EG, Iwata KK, Arnold L, Boman B, Cunningham A, DiOrio C, Doty J, Morin MJ, Moyer MP et al. 1997 Induction of apoptosis and cell cycle arrest by CP-358, 774, an inhibitor of epidermal growth factor receptor tyrosine kinase. Cancer Research 57 4838–4848.

[88] ↵

Naramura M, Gillies SD, Mendelsohn J, Reisfeld RA & Mueller BM 1993 Therapeutic potential of chimeric and murine anti-(epidermal growth factor receptor) antibodies in a metastasis model for human melanoma. Cancer Immunology and Immunotherapy 37 343–349.

[89] ↵

Needle MN 2002 Safety experience with IMC-C225, an anti-epidermal growth factor receptor antibody. Seminars in Oncology 29 55–60.

[90] ↵

Nicholson RI, Gee JM & Harper ME 2001 EGFR and cancer prognosis. European Journal of Cancer 37 (Suppl 4) S9–S15.

[91] ↵

Paez JG, Janne PA, Lee JC, Tracy S, Greulich H, Gabriel S, Herman P, Kaye FJ, Lindeman N, Boggon TJ et al. 2004 EGFR mutations in lung cancer:correlation with clinical response to gefitinib therapy. Science 304 1497–1500.

[92] Perez-Soler R, Chachoua A, Huberman M, Karp D, Rigas J, Hammond L, Rowinsky E, Preston D, Ferrante KJ, Allen LF et al. 2001 A phase II trial of the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor OSI-774, following platinum-based chemotherapy, in patients (pts) with advanced, EGFR-expressing, non-small cell lung cancer (NSCLC). Proceedings of the American Society of Clinical Oncology 21 309a Abstract 1235.

[93] ↵

Perrotte P, Matsumoto T, Inoue K, Kuniyasu H, Eve BY, Hicklin DJ, Radinsky R & Dinney CP 1999 Anti-epidermal growth factor receptor antibody C225 inhibits angiogenesis in human transitional cell carcinoma growing orthotopically in nude mice. Clinical Cancer Research 5 257–265.

[94] ↵

Pollack VA, Savage DM, Baker DA, Tsaparikos KE, Sloan DE, Moyer JD, Barbacci EG, Pustilnik LR, Smolarek TA, Davis JA et al. 1999 Inhibition of epidermal growth factor receptor-associated tyrosine phosphorylation in human carcinomas with CP-358, 774:dynamics of receptor inhibition in situ and antitumor effects in athymic mice. Journal of Pharmacology and Experimental Therapeutics 291 739–748.

[95] ↵

Prados M, Chang S, Burton A, Kapadia A, Rabbitt J, Page M, Federoff A, Kelly S & Fyfe G 2003 Phase I study of OSI-774 alone or with temozolomide in patients with malignant glioma. Proceedings of the American Society of Clinical Oncology 22 99 Abstract 394.

[96] ↵

Prewett M, Rockwell P, Rockwell RF, Giorgio NA, Mendelsohn J, Scher HI & Goldstein NI 1996 The biologic effects of C225, a chimeric monoclonal antibody to the EGFR, on human prostate carcinoma. Journal of Immunotherapy with Emphasis on Tumor Immunology 19 419–427.

[97] ↵

Prewett M, Rothman M, Waksal H, Feldman M, Bander NH & Hicklin DJ 1998 Mouse-human chimeric anti-epidermal growth factor receptor antibody C225 inhibits the growth of human renal cell carcinoma xenografts in nude mice. Clinical Cancer Research 4 2957–2966.

[98] ↵

Prewett M, Overholser J, Hooper A & Waksal HH 1999 Growth inhibition of human pancreatic carcinoma in vitro and in vivo by chimeric anti-EGF receptor monoclonal antibody C225. Proceedings of the American Association for Cancer Research 40 730 Abstract 4818.

[99] ↵

Qu CK 2002 Role of the SHP-2 tyrosine phosphatase in cytokine-induced signaling and cellular response. Biochimica et Biophysica Acta 1592 297–301.

[100] ↵

Ranson M, Hammond LA, Ferry D, Kris M, Tullo A, Murray PI, Miller V, Averbuch S, Ochs J, Morris C et al. 2002 ZD1839, a selective oral epidermal growth factor receptor-tyrosine kinase inhibitor, is well tolerated and active in patients with solid, malignant tumors:results of a phase I trial. Journal of Clinical Oncology 20 2240–2250.

[101] ↵

Robert F, Ezekiel MP, Spencer SA, Meredith RF, Bonner JA, Khazaeli MB, Saleh MN, Carey D, LoBuglio AF, Wheeler RH et al. 2001 Phase I study of anti-epidermal growth factor receptor antibody cetuximab in combination with radiation therapy in patients with advanced head and neck cancer. Journal of Clinical Oncology 19 3234–3243.

[102] ↵

Robert F, Blumenschein G, Dicke K, Tseng J, Saleh MN & Needle M 2003 Phase IB/IIA study of anti-epidermal growth factor receptor antibody, cetuximab, in combination with gemcitabine/carboplatin in patients with advanced stage IV non-small cell lung cancer. Proceedings of the American Society of Clinical Oncology 22 643 Abstract 2587.

[103] ↵

Robertson JFR, Gutteridge E, Cheung KL, Owers R, Koehler M, Hamilton L, Gee J, Nicholson RI 2003 Gefitinib (‘Iressa ’, ZD1839) is active in acquired tamoxifen (TAM)-resistant oestrogen receptor (ER)-positive and ER-negative breast cancer:results from a phase II study. Proceedings of the American Society of Clinical Oncology 22 7 Abstract 23.

[104] ↵

Rosenberg AH, Loehrer PJ, Needle MN, Waksal H, Hollywood E, Ramos L & Saltz LB 2002 Erbitux (IMC-C225) plus weekly irinotecan (CPT-11), fluorouracil (5FU) and leucovorin (LV) in colorectal cancer (CRC) that expresses the epidermal growth factor receptor (EGFR). Proceedings of the American Society of Clinical Oncology 21 135a Abstract 536.

[105] ↵

Roskos L, Lohner M, Osborn K, Pasumarthi R, Lu H, Funelas C, Raie N, Yang X-D, Weiner L, Figlin RA et al. 2002 Low pharmacokinetic variability facilitates optimal dosing of ABX-EGF in cancer patients. Proceedings of the American Society of Clinical Oncology 21 91a Abstract 362.

[106] ↵

Salomon DS, Brandt R, Ciardiello F & Normanno N 1995 Epidermal growth factor-related peptides and their receptors in human malignancies. Critical Reviews in Oncology/Hematology 19 183–232.

[107] ↵

Saltz L, Rubin M, Hochster H, Tchekmeydian NS, Waksal H, Needle M & LoBuglio A 2001 Cetuximab (IMC-C225) plus irinotecan (CPT-11) is active in CPT-11-refractory colorectal cancer (CRC) that expresses epidermal growth factor receptor (EGFR). Proceedings of the American Society of Clinical Oncology 20 3a Abstract 7.

[108] Saltz L, Meropol NJ, Loehrer PJ, Waksal H, Needle MN & Mayer RJ 2002 Single agent IMC-C225 (Erbitux(tm)) has activity in CPT-11-refractory colorectal cancer (CRC) that expresses the epidermal growth factor receptor (EGFR). Proceedings of the American Society of Clinical Oncology 21 127a Abstract 504.

[109] ↵

Saltz L, Kies M, Abbruzzese JL, Azarnia N & Needle M 2003 The presence and intensity of the cetuximab-induced acne-like rash predicts increased survival in studies across multiple malignancies. Proceedings of the American Society of Clinical Oncology 22 204 Abstract 817.

[110] ↵

Saul H 2003 27th ESMO Congress, Nice, 18–22 October 2002. Iressa disappoints in NSCLC. European Journal of Cancer 39 1.

[111] ↵

Schoffski P, Lutz MP, Folprecht G, Beutel G, Seufferlein T, Marschner JP, Harstrick A & Kohne CH 2002 Cetuximab (C225) plus irinotecan (CPT-11) plus infusional 5FU-folinic acid (FA) is safe and active in metastatic colorectal cancer (MCRC), that expresses epidermal growth factor receptor (EGFR). Proceedings of the American Society of Clinical Oncology 21 159a Abstract 633.

[112] ↵

Schultz J 2003 Apparent adverse drug reactions prompt concern about Iressa. Journal of the National Cancer Institute 95 577–579.

[113] ↵

Schwartz G, Dutcher J, Vogelzang N, Gollob J, Thompson J, Bukowski RM, Figlin RA, Lohner M, Roskos L, Hwang CC et al. 2002 Phase 2 clinical trial evaluating the safety and effectiveness of ABX-EGF in renal cell cancer (RCC). Proceedings of the American Society of Clinical Oncology 21 Abstract 91.

[114] ↵

Shepherd FA, Pereira J, Ciuleanu TE, Tan EH, Hirsh V, Thongprasert S, Bezjak A, Tu D, Santabarbara P & Seymour L 2004 A randomized placebo-controlled trial of erlotinib in patients with advanced non-small cell lung cancer (NSCLC) following failure of 1st line or 2nd line chemotherapy. A National Cancer Institute of Canada Clinical Trials Group (NCIC CTG) trial. Proceedings of the American Society of Clinical Oncology 23 . Abstract 7022.

[115] ↵

Shin DM, Donato NJ, Perez-Soler R, Shin HJ, Wu JY, Zhang P, Lawhorn K, Khuri FR, Glisson BS, Myers J et al. 2001 Epidermal growth factor receptor-targeted therapy with C225 and cisplatin in patients with head and neck cancer. Clinical Cancer Research 7 1204–1213.

[116] ↵

Sirotnak FM 2003 Studies with ZD1839 in preclinical models. Seminars in Oncology 30 12–20.

[117] ↵

Sirotnak FM, Zakowski MF, Miller VA, Scher HI & Kris MG 2000 Efficacy of cytotoxic agents against human tumor xenografts is markedly enhanced by coadministration of ZD1839 (Iressa), an inhibitor of EGFR tyrosine kinase. Clinical Cancer Research 6 4885–4892.

[118] ↵

Sorkina T, Huang F, Beguinot L & Sorkin A 2002 Effect of tyrosine kinase inhibitors on clathrin-coated pit recruitment and internalization of epidermal growth factor receptor. Journal of Biological Chemistry 277 27433–27441.

[119] ↵

Soulieres D, Senzer NN, Vokes EE, Hidalgo M, Agarwala SS & Siu LL 2004 Multicenter phase II study of erlotinib, an oral epidermal growth factor receptor tyrosine kinase inhibitor, in patients with recurrent or metastatic squamous cell cancer of the head and neck. Journal of Clinical Oncology 22 77–85.

[120] ↵

Toyoda H, Komurasaki T, Uchida D & Morimoto S 1997 Distribution of mRNA for human epiregulin, a differentially expressed member of the epidermal growth factor family. Biochemical Journal 326 69–75.

[121] ↵

Van Laethem J-L, Raoul J-L, Mitry E, Brezault C, Husseini F, Cals L, Vedovato JC, Mueser MM & Rougier P 2003 Cetuximab (C225) in combination with bi-weekly irinotecan (CPT-11), infusional 5-fluorouracil (5-FU), and folinic acid (FA) in patients with metastatic colorectal cancer (CRC) expressing the epidermal growth factor receptor (EGFR). Preliminary safety and efficacy results. Proceedings of the American Society of Clinical Oncology 22 264 Abstract 1058.

[122] ↵

Vega-Villegas E, Awada R, Mesia L Geoffrois L, Borel C, Humblet Y, Lopez-Poussa A, Hitt R, Amellal N & Bourhis J 2003 A phase I study of cetuximab in combination with cisplatin or carboplatin and 5-FU in patients with recurrent or metastatic squamous cell carcinoma of the head and neck. Proceedings of the American Association for Cancer Research 22 502 Abstract 2020.

[123] ↵

Viens P, L ’Homme C, Extra JM, Gladieff L, Kalla S & Fabbro M 2003 A phase II trial to evaluate efficacy and safety of gefitinib (ZD1836) in patients with loco-regionally advanced or metastatic squamous cell carcinoma of the cervix. Proceedings of the American Society of Clinical Oncology 22 456 Abstract 1833.

[124] ↵

Viloria-Petit AM, Rak J, Hung MC, Rockwell P, Goldstein N, Fendly B & Kerbel RS 1997 Neutralizing antibodies against epidermal growth factor and ErbB-2/neu receptor tyrosine kinases down-regulate vascular endothelial growth factor production by tumor cells in vitro and in vivo:angiogenic implications for signal transduction therapy of solid tumors. American Journal of Pathology 151 1523–1530.

[125] Wang P, Fredlin P, Davis CG & Yang X-D 2002 Therapeutic potential of ABX-EGF, a fully human anti-EGF receptor monoclonal antibody for the treatment of renal cell carcinoma. Proceedings of the American Society of Clinical Oncology 21 191a Abstract 761.

[126] ↵

Wang P, Fredlin P, Davis CG & Yang X-D 2003 Human anti-EGF receptor monoclonal antibody ABX-EGF:a potential monotherapy for the treatment of prostate cancer. Proceedings of the American Society of Clinical Oncology 22. Abstract 4525.

[127] ↵

Watanabe T, Shintani A, Nakata M, Shing Y, Folkman J, Igarashi K & Sasada R 1994 Recombinant human betacellulin. Molecular structure, biological activities, and receptor interaction. Journal of Biological Chemistry 269 9966–9973.

[128] ↵

Wells A 1999 EGF receptor. International Journal of Biochemistry and Cell Biology 31 637–643.

[129] ↵

Wiley HS 2003 Trafficking of the ErbB receptors and its influence on signaling. Experimental Cell Research 284 78–88.

[130] ↵

Woodburn JR 1999 The epidermal growth factor receptor and its inhibition in cancer therapy. Pharmacology and Therapeutics 82 241–250.

[131] ↵

Woodburn JR, Kendrew J, Fennell M & Wakeling AE 2000 ZD1839 (‘IRESSA ’) A selective epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI):inhibition of c-fos mRNA, an intermediate marker of EGFR activation, correlates with tumor growth inhibition. Proceedings of the American Association for Cancer Research 41 402 Abstract 2552.

[132] ↵

Yang XD, Jia XC, Corvalan JR, Wang P, Davis CG & Jakobovits A 1999 Eradication of established tumors by a fully human monoclonal antibody to the epidermal growth factor receptor without concomitant chemotherapy. Cancer Research 59 1236–1243.

[133] ↵

Yang XD, Jia XC, Corvalan JR, Wang P & Davis CG 2001 Development of ABX-EGF, a fully human anti-EGF receptor monoclonal antibody, for cancer therapy. Critical Reviews in Oncology/Hematology 38 17–23.

[134] ↵

Yarden Y 2001 The EGFR family and its ligands in human cancer:signalling mechanisms and therapeutic opportunities. European Journal of Cancer 37 (Suppl 4) S3–S8.

[135] ↵

Yarden Y & Sliwkowski MX 2001 Untangling the ErbB signalling network. Nature Reviews. Molecular Cell Biology 2 127–137.

Endocrine-Related Cancer

References

This Article

New Articles: issue in progress

Most

Viewed

Cited