Clinical trial design and end points for epidermal growth factor receptor-targeted therapies: Implications for drug development and practice

Clinical Cancer Research

Volumn 9, Issue 5, 2003, Pages 1579-1589

  Arteaga, Carlos L ^a,d   Baselga, Jose ^b,c  

^a VANDERBILT INGRAM CANCER CENTER   (United States)

^b HOSPITAL UNIVERSITARI VALL D HEBRON   (Spain)

^c UNIVERSITAT AUTÒNOMA DE BARCELONA   (Spain)

^d VANDERBILT UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

4 (3 BROMOANILINO) 6,7 DIMETHOXYQUINAZOLINE; 6 (4 HYDROXYPHENYL) 4 (ALPHA METHYLBENZYLAMINO) 7H PYRROLO[2,3 D]PYRIMIDINE; ADENOSINE TRIPHOSPHATASE INHIBITOR; CANERTINIB; CETUXIMAB; CISPLATIN; CYCLIN DEPENDENT KINASE INHIBITOR; CYTOTOXIC AGENT; EPIDERMAL GROWTH FACTOR RECEPTOR; EPIDERMAL GROWTH FACTOR RECEPTOR ANTIBODY; EPIDERMAL GROWTH FACTOR RECEPTOR KINASE; ERLOTINIB; FULVESTRANT; GEFITINIB; H R3; IMC 225; LAPATINIB; MATUZUMAB; MDX 447; MONOCLONAL ANTIBODY 806; PELITINIB; PROTEIN TYROSINE KINASE INHIBITOR; TAMOXIFEN; TRASTUZUMAB; UNCLASSIFIED DRUG;

ANTINEOPLASTIC ACTIVITY; BLADDER CANCER; BREAST CANCER; BREAST METASTASIS; CANCER CHEMOTHERAPY; CLINICAL TRIAL; COLON CANCER; COMPETITIVE INHIBITION; CYTOTOXICITY; DIMERIZATION; DOWN REGULATION; DRUG ACTIVITY; DRUG BIOAVAILABILITY; DRUG CLEARANCE; DRUG HALF LIFE; DRUG INDICATION; DRUG INDUCED DISEASE; DRUG RECEPTOR BINDING; DRUG SAFETY; DRUG TARGETING; GASTROINTESTINAL TOXICITY; GENE AMPLIFICATION; GENE FUNCTION; GENE TARGETING; HEAD CANCER; HUMAN; LUNG CANCER; LUNG NON SMALL CELL CANCER; MAXIMUM TOLERATED DOSE; NECK CANCER; NONHUMAN; ONCOGENE NEU; PATIENT SELECTION; PHARMACODYNAMICS; PRIORITY JOURNAL; PROTEIN BINDING; PROTEIN DOMAIN; SHORT SURVEY; SIDE EFFECT; SQUAMOUS CELL CARCINOMA;

ANTINEOPLASTIC AGENTS; CLINICAL TRIALS; DISEASE MANAGEMENT; DRUG DELIVERY SYSTEMS; HUMANS; NEOPLASMS; RECEPTOR, EPIDERMAL GROWTH FACTOR; RESEARCH DESIGN; TREATMENT OUTCOME;

EID: 0038666476     PISSN: 10780432     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Short Survey

References (111)

1. Mendelsohn, J., and Baselga, J. The EGF receptor family as targets for cancer therapy. Oncogene, 19: 6550-6565, 2000.
2. Fan, Z., Masui, H., Altas, I., and Mendelsohn, J. Blockade of epidermal growth factor receptor function by bivalent and monovalent fragments of 225 anti-epidermal growth factor receptor monoclonal antibodies. Cancer Res., 53: 4322-4328, 1993.
3. Fan, Z., Lu, Y., Wu, X., and Mendelsohn, J. Antibody-induced epidermal growth factor receptor dimerization mediates inhibition of autocrine proliferation of A431 squamous carcinoma cells. J. Biol. Chem., 269: 27595-27602, 1994.
4. Rodeck, U., Herlyn, M., Herlyn, D., Molthoff, C., Atkinson, B., Varello, M., Steplewski, Z., and Koprowski, H. Tumor growth modulation by a monoclonal antibody to the epidermal growth factor receptor: immunologically mediated and effector cell-independent effects. Cancer Res., 47: 3692-3696, 1987.
5. Modjtahedi, H., Eccles, S., Sandle, J., Box, G., Titley, J., and Dean, C. Differentiation or immune destruction: two pathways for therapy of squamous cell carcinomas with antibodies to the epidermal growth factor receptor. Cancer Res., 54: 1695-1701, 1994.
6. Bier, H., Hoffmann, T., Haas, I., and van Lierop, A. 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. Cancer Immunol. Immunother., 46: 167-173, 1998.
7. Clynes, R. A., Towers, T. L., Presta, L. G., and Ravetch, J. V. Inhibitory Fc receptors modulate in vivo cytotoxicity against tumor targets. Nat. Med., 6: 443-446, 2000.
8. Toledo, L. M., Lydon, N. B., and Elbaum, D. The structure-based design of ATP-site directed protein kinase inhibitors. Curr. Med. Chem., 6: 775-805, 1999.
9. Al-Abeidi, F., and Lain K. S. Development of inhibitors for protein tyrosine kinases. Oncogene, 19: 5690-5701, 2000.
10. Arteaga, C. L., Ramsey, T. T., Shawver, L. K., and Guyer, C. A. Unliganded epidermal growth factor receptor dimerization induced by direct interaction of quinazolines with the ATP binding site. J. Biol. Chem., 272: 23247-23254, 1997.
11. Lichtner, R. B., Menrad, A., Sommer, A., Klar, U., and Schneider, M. R. Signaling-inactive epidermal growth factor receptor/ligand complexes in intact carcinoma cells by quinazoline tyrosine kinase inhibitors. Cancer Res., 61: 5790-5795, 2001.
12. Yarden, Y., and Sliwkowski, M. X. Untangling the ErbB signalling network. Nat. Rev. Mol. Cell. Biol., 2: 127-137, 2001.
13. Olayioye, M. A., Neve, R. M., Lane, H. A., and Hynes, N. E. The ErbB signaling network: receptor heterodimerization in development and cancer. EMBO J., 19: 3159-3167, 2000.
14. Fry, D. W. Site-directed irreversible inhibitors of the erbB family of receptor tyrosine kinases as novel chemotherapeutic agents for cancer. Anticancer Drug Des., 15: 3-16, 2000.
15. Baselga, J., Pfister, D., Cooper, M. R., Cohen, R., Burtness, B., Bos, M., D'Andrea, G., Seidman, A., Norton, L., Gunnett, K., Falcey, J., Anderson, V., Waksal, H., and Mendelsohn, J. Phase I studies of anti-epidermal growth factor receptor chimeric antibody C225 alone and in combination with cisplatin. J. Clin. Oncol., 18: 904-914, 2000.
16. Hidalgo, M., Siu, L. L., Nemunaitis, J., Rizzo, J., Hammond, L. A., Takimoto, C., Eckhardt, S. G., Tolcher, A., Britten, C. D., Denis, L., Ferrante, K., Von Hoff, D. D., Silberman, S., and Rowinsky, E. K. Phase I and pharmacologic study of OSI-774, an epidermal growth factor receptor tyrosine kinase inhibitor, in patients with advanced solid malignancies. J. Clin. Oncol., 19: 3267-3279, 2001.
17. Ranson, M., Hammond, L. A., Ferry, D., Kris, M., Tullo, A., Murray, P. I., Miller, V., Averbuch, S., Ochs, J., Morris, C., Feyereislova, A., Swaisland, H., and Rowinsky, E. K. 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. J. Clin. Oncol., 20: 2240-2250, 2002.
18. Baselga, J., Rischin, D., Ranson, M., Calvert, H., Raymond, E., Kieback, D. G., Kaye, S. B., Gianni, L., Harris, A., Bjork, T., Averbuch, S. D., Feyereislova, A., Swaisland, H., Rojo, F., and Albanell, J. Phase I safety, pharmacokinetic, and pharmacodynamic trial of ZD1839, a selective oral epidermal growth factor receptor tyrosine kinase inhibitor, in patients with five selected solid tumor types. J. Clin. Oncol., 20: 4292-4302, 2002.
19. Schwartz, G., Dutcher, J. P., Vogelzang, N. J., Gollob, J., Thompson, J., Bukowski, R. M., Figlin, R. A., Lohner, M., Roskos, L., Hwang, C. C., Foon, K., Schwab, G., and Rowinsky, E. Phase 2 clinical trial evaluating the safety and effectiveness of ABX-EGF in renal cell cancer (RCC). Proc. Am. Soc. Clin. Oncol., 21: 24, 2002.
20. Saltz, L., Meropol, N. J., Loehrer, P. J., Waksal, H., Needle, M. N., and Mayer, R. J. Single agent IMC-C225 (Erbitux) has activity in CPT-11-refractory colorectal cancer (CRC) that expresses the epidermal growth factor receptor (EGFR). Proc. Am. Soc. Clin. Oncol., 21: 127, 2002.
21. Martinez-Lacaci, I., Kannan, S., De Santis, M., Bianco, C., Kim, N., Wallace-Jones, B., Ebert, A. D., Wechselberger, C., and Salomon, D. S. RAS transformation causes sustained activation of epidermal growth factor receptor and elevation of mitogen-activated protein kinase in human mammary epithelial cells. Int. J. Cancer, 88: 44-52, 2000.
22. Bos, M., Mendelsohn, J., Kim, Y. M., Albanell, J., Fry, D. W., and Baselga, J. PD153035, a tyrosine kinase inhibitor, prevents epidermal growth factor receptor activation and inhibits growth of cancer cells in a receptor number-dependent manner. Clin. Cancer Res., 3: 2099-2106, 1997.
23. Salomon, D. S., Brandt, R., Ciardiello, F., and Normanno, N. Epidermal growth factor-related peptides and their receptors in human malignancies. Crit. Rev. Oncol. Hematol., 19: 183-232, 1995.
24. Rusch, V., Baselga, J., Cordon-Cardo, C., Orazem, J., Zaman, M., Hoda, S., McIntosh, J., Kurie, J., and Dmitrovsky, E. Differential expression of the epidermal growth factor receptor and its ligands in primary non-small cell lung cancers and adjacent benign lung. Cancer Res., 53: 2379-2385, 1993.
25. Grandis, J. R., Melhem, M. F., Gooding, W. E., Day, R., Holst, V. A., Wagener, M. M., Drenning, S. D., and Tweardy, D. J. Levels of TGF-alpha and EGFR protein in head and neck squamous cell carcinoma and patient survival. J. Natl. Cancer Inst. (Bethesda), 90: 824-832, 1998.
26. Fontanini, G., De Laurentiis, M., Vignati, S., Chine, S., Lucchi, M., Silvestri, V., Mussi, A., De Placido, S., Tortora, G., Bianco, A. R., Gullick, W., Angeletti, C. A., Bevilacqua, G., and Ciardiello, F. Evaluation of epidermal growth factor-related growth factors and receptors and of neoangiogenesis in completely resected stage I-IIIA non-smallcell lung cancer: amphiregulin and microvessel count are independent prognostic indicators of survival. Clin. Cancer Res., 4: 241-249, 1998.
27. Divgi, C. R., Welt, S., Kris, M., Real, F. X., Yeh, S. D., Gralla, R., Merchant, B., Schweighart, S., Unger, M., Larson, S. M., et al. Phase I and imaging trial of indium 111-labeled anti-epidermal growth factor receptor monoclonal antibody 225 in patients with squamous cell lung carcinoma. J. Natl. Cancer Inst. (Bethesda), 83: 97-104, 1991.
28. Sirotnak, F. M., Zakowski, M. F., Miller, V. A., Scher, H. I., and Kris, M. G. Efficacy of cytotoxic agents against human tumor xenografts is markedly enhanced by coadministration of ZD1839 (Iressa), an inhibitor of EGFR tyrosine kinase. Clin. Cancer Res., 6: 4885-4892, 2000.
29. Ciardiello, F., Caputo, R., Bianco, R., Damiano, V., Pomatico, G., De Placido, S., Bianco, A. R., and Tortora, G. Antitumor effect and potentiation of cytotoxic drugs activity in human cancer cells by ZD1839 (Iressa), an epidermal growth factor receptor-selective tyrosine kinase inhibitor. Clin. Cancer Res., 6: 2053-2063, 2000.
30. Saltz, L., Rubin, M., Hochster, H., Tchekmeydian, N. S., Waksal, H., Needle, M., and LoBuglio, A. Cetuximab (IMC-225) plus irinotecan (CPT-11) is active in CPT-11-refractory colorectal cancer that expresses epidermal growth factor receptors. Proc. Am. Soc. Clin. Oncol., 20: 3, 2001.
31. Moasser, M. M., Basso, A., Averbuch, S. D., and Rosen, N. The tyrosine kinase inhibitor ZD1839 ("Iressa") inhibits HER2-driven signaling and suppresses the growth of HER2-overexpressing tumor cells. Cancer Res., 61: 7184-7188, 2001.
32. Moulder, S. L., Yakes, F. M., Muthuswamy, S. K., Bianco, R., Simpson, J. F., and Arteaga, C. L. Epidermal growth factor receptor (HER1) tyrosine kinase inhibitor (Iressa) inhibits HER2/neu (erbB2)overexpressing breast cancer cells in vitro and in vivo. Cancer Res., 61: 8887-8895, 2001.
33. Rusch, V., Klimstra, D., Linkov, I., and Dmitrovsky, E. Aberrant expression of p53 or the epidermal growth factor receptor is frequent in early bronchial neoplasia and coexpression precedes squamous cell carcinoma development. Cancer Res., 55: 1365-1372, 1995.
34. Kurie, J. M., Shin, H. J., Lee, J. S., Morice, R. C., Ro, J. Y., Lippman, S. M., Hittelman, W. N., Yu, R., Lee, J. J., and Hong, W. K. Increased epidermal growth factor receptor expression in metaplastic bronchial epithelium. Clin. Cancer Res., 2: 1787-1793, 1996.
35. van de Vijver, M. J., Peterse, J. L., Mooi, W. J., Wisman, P., Lomans, J., Dalesio, O., and Nusse, R. Neu-protein overexpression in breast cancer. Association with comedo-type ductal carcinoma in situ and limited prognostic value in stage II breast cancer. N. Engl. J. Med., 319: 1239-1245, 1988.
36. Lenferink, A. E., Simpson, J. F., Shawver, L. K., Coffey, R. J., Forbes, J. T., and Arteaga, C. L. Blockade of the epidermal growth factor receptor tyrosine kinase suppresses tumorigenesis in MMTV/Neu + MMTV/TGF-α bigenic mice. Proc. Natl. Acad. Sci. USA, 97: 9609-9614, 2000.
37. Roberts, R. B., Min, L., Washington, M. K., Olsen, S. J., Settle, S. H., Coffey, R. J., and Threadgill, D. W. Importance of epidermal growth factor receptor signaling in establishment of adenomas and maintenance of carcinomas during intestinal tumorigenesis. Proc. Natl. Acad. Sci. USA, 99: 1521-1526, 2002.
38. Chan, K. C., Knox, W. F., Gee, J. M., Morris, J., Nicholson, R. I., Potten, C. S., and Bundred, N. J. Effect of epidermal growth factor receptor tyrosine kinase inhibition on epithelial proliferation in normal and premalignant breast. Cancer Res., 62: 122-128, 2002.
39. Wu, X., Fan, Z., Masui, H., Rosen, N., and Mendelsohn, J. Apoptosis induced by an anti-epidermal growth factor receptor monoclonal antibody in a human colorectal carcinoma cell line and its delay by insulin. J Clin. Investig., 95: 1897-1905, 1995.
40. Wakeling, A. E., Guy, S. P., Woodburn, J. R., Ashton, S. E., Curry, B. J., Barker, A. J., and Gibson, K. H. ZD1839 (Iressa): an orally active inhibitor of epidermal growth factor signaling with potential for cancer therapy. Cancer Res., 62: 5749-5754, 2002.
41. Baselga, J., Tripathy, D., Mendelsohn, J., Baughman, S., Benz, C. C., Dantis, L., Sklarin, N. T., Seidman, A. D., Hudis, C. A., Moore, J., Rosen, P. P., Twaddell, T., Henderson, I. C., and Norton, L. Phase II study of weekly intravenous recombinant humanized anti-p185HER2 monoclonal antibody in patients with HER2/neu-overexpressing metastatic breast cancer. J. Clin. Oncol., 14: 737-744, 1996.
42. Cobleigh, M. A., Vogel, C. L., Tripathy, D., Robert, N. J., Scholl, S., Fehrenbacher, L., Wolter, J. M., Paton, V., Shak, S., Lieberman, G., and Slamon, D. J. Multinational study of the efficacy and safety of humanized anti-HER2 monoclonal antibody in women who have HER2overexpressing metastatic breast cancer that has progressed after chemotherapy for metastatic disease. J. Clin. Oncol., 17: 2639-2648, 1999.
43. Vogel, C. L., Cobleigh, M. A., Tripathy, D., Gutheil, J. C., Harris, L. N., Fehrenbacher, L., Slamon, D. J., Murphy, M., Novotny, W. F., Burchmore, M., Shak, S., Stewart, S. J., and Press, M. Efficacy and safety of trastuzumab as a single agent in first-line treatment of HER2overexpressing metastatic breast cancer. J. Clin. Oncol., 20: 719-726, 2002.
44. Fukuoka, M., Yano, S., Giaccone, G., Tamura, T., Nakagawa, K., Douillard, J-Y., Nishiwaki, Y., Vansteenkiste, J., Kudoh, S., Rischin, D., Eek, R., Horai, T., Noda, K., Takata, I., Smit, E., Averbuch, S., MacLeod, A., Feyereislova, A., Dong, R-P., and Baselga, J. A multiinstitutional randomized Phase II trial of gefitinib for previously treated patients with advanced non-small-cell lung cancer (the IDEAL I trial). J. Clin. Oncol., 21: in press, 2003.
45. Kris, M. G., et al. A Phase II trial of ZD1839 ('Iressa') in advanced non-small-cell lung cancer (NSCLC) patients who have failed platinumand docetaxel-based regimens. J. Clin. Oncol., 21: in press. 2003.
46. Perez-Soler, R., Chachoua, A., Huberman, M., Karp, D., Rigas, J., Hammond, L., Rowinsky, E., Preston, G., Ferrante, K. J., Allen, L. F., Nadler, P. I., and Bonomi, P. A Phase II trial of the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor OSI-774. after platinum-based chemotherapy, in patients (pts) with advanced, EGFR-expressing, non-small cell lung cancer (NSCLC). Proc. Am. Soc. Clin. Oncol., 20: 310a, 2001.
47. Slamon, D. J., Leyland-Jones, B., Shak, S., Fuchs, H., Paton, V., Bajamonde, A., Fleming, T., Eiermann, W., Wolter, J., Pegram, M., Baselga, J., and Norton, L. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N. Engl. J. Med., 344: 783-792, 2001.
48. Giaccone, g., Johnson, D. H., Manegold, C., Scagliotti, G. V., Rosell, R., Wolf, M., Rennie, P., Ochs, J., Averbuch, S., and Fandi, A. A. Phase III clinical trial of ZD1839 ('Iressa') in combination with gemcitabine and cisplatin in chemotherapy-naive patients with advances non-small-cell lung cancer (INTACT 1). Ann. Oncol., 13 (Suppl. 5): 2, 2002.
49. Johnson, D. H., Herbst, R., Giaconne, G., Schiller, J., Natale, R. B., Miller, V., Wolf, M., Helton, A., Averbuch, S., and Grous, J. Z. D.1839 ("Iressa") in combination with paclitaxel and carboplatin in chemotherapy-naive patients with advanced non-small-cell lung cancer (NSCLC): results from a Phase III clinical trial (INTACT 2). Ann. Oncol., 13 (Suppl. 5): 127, 2002.
50. Burtness, B., Li, Y., Flood, W., Mattar, B. I., and Forastiere, A. A. Phase III trial comparing cisplatin (C) + placebo to C + anti-epidermal growth factor receptor (EGF-R) antibody C225 in patients (pts) with metastatic/recurrent head and neck cancer (HNC). Proc. Am. Soc. Clin. Oncol., 21: 226, 2002.
51. Kelly, H. C., Laight, A., Morris, C. Q., Woodburn, J. R., and Richmond, G. H. P. Phase I data of ZD 1839 - an oral epidermal growth factor receptor tyrosine kinase inhibitor. Ann. Oncol., 2: 109, 1998.
52. Sato, J. D., Kawamoto, T., Le, A. D., Mendelsohn, J., Polikoff, J., and Sato, G. H. Biological effects in vitro of monoclonal antibodies to human epidermal growth factor receptors. Mol. Biol. Med., 1: 511-529, 1983.
53. Kawamoto, T., Mendelsohn, J., Le, A., Sato, G. H., Lazar, C. S., and Gill, G. N. Relation of epidermal growth factor receptor concentration to growth of human epidermoid carcinoma A431 cells. J. Biol. Chem., 259: 7761-7766, 1984.
54. Albanell, J., Rojo, F., Averbuch, S., Feyereislova, A., Mascaro, J. M., Herbst, R., LoRusso, P., Rischin, D., Sauleda, S., Gee, J., Nicholson, R. I., and Baselga, J. Pharmacodynamic studies of the epidermal growth factor receptor inhibitor ZD1839 in skin from cancer patients: histopathologic and molecular consequences of receptor inhibition. J. Clin. Oncol., 20: 110-124, 2002.
55. Klijn, J. G., Berns, P. M., Schmitz, P. I., and Foekens, J. A. The clinical significance of epidermal growth factor receptor (EGF-R) in human breast cancer: a review on 5232 patients. Endocr. Rev., 13: 3-17, 1992.
56. Sharma, A. K., Horgan, K., Douglas-Jones, A., McClelland, R., Gee, J., and Nicholson, R. Dual immunocytochemical analysis of oestrogen and epidermal growth factor receptors in human breast cancer. Br. J. Cancer, 69: 1032-1037, 1994.
57. Ellis, P. A., Saccani-Jotti, G., Clarke, R., Johnston, S. R., Anderson, E., Howell, A., A'Hern, R., Salter, J., Detre, S., Nicholson, R., Robertson, J., Smith, I. E., and Dowsett, M. Induction of apoptosis by tamoxifen and ICI 182780 in primary breast cancer. Int. J. Cancer. 72: 608-613, 1997.
58. Chang, J., Powles, T. J., Allred, D. C., Ashley, S. E., Makris, A., Gregory, R. K., Osborne, C. K., and Dowsett, M. Prediction of clinical outcome from primary tamoxifen by expression of biologic markers in breast cancer patients. Clin. Cancer Res., 6: 616-621, 2000.
59. Robertson, J. F., Nicholson, R. I., Bundred, N. J., Anderson, E., Rayter, Z., Dowsett, M., Fox, J. N., Gee, J. M., Webster, A., Wakeling, A. E., Morris, C., and Dixon, M. Comparison of the short-term biological effects of 7α-[9-(4,4,5,5,5-pentafluoropentylsulfinyl)-nonyl]estra1,3,5, (10)-triene-3,17β-diol (Faslodex) versus tamoxifen in postmenopausal women with primary breast cancer. Cancer Res., 61: 6739-6746, 2001.
60. Rubin, M., Shin, D., Pasmantier, M., Falcey, J. W., Paulter, V. J., Fetzer, K. M., Waksal, H. W., Mendelsohn, J., and Hong, W. K. Monoclonal antibody (MoAb) IMC-225, an anti-epidermal growth factor receptor (EGFR) for patients with EGFR-positive tumors refractory to or in relapse from previous therapeutic regimens. Proc. Am. Soc. Clin. Oncol., 19: 474a, 2000.
61. Prewett, M. C., Hooper, A. T., Bassi, R., Ellis, L. M., Waksal, H. W., and Hicklin, D. J. Enhanced antitumor activity of anti-epidermal growth factor receptor monoclonal antibody IMC-C225 in combination with irinotecan (CPT-11) against human colorectal tumor xenografts. Clin. Cancer Res., 8: 994-1003, 2002.
62. Baselga, J. M., Trigo, J., Bourhis, J., Tortochaux, J., Cortes-Funes, H., Hitt, R., Gascon, P., Muesser, M., Harstrick, A., and Eckardt, A. Cetuximab (C225) plus cisplatin/carboplatin is active in patients with recurrent/metastatic squamous cell carcinoma of the head and neck (SCCHN) progressing on a same dose and schedule platinum-based regimen. Proc. Am. Soc. Clin. Oncol., 21: 226, 2002.
63. Albanell, J., Codony-Servat, J., Rojo, F., Del Campo, J. M., Sauleda, S., Anido, J., Raspall, G., Giralt, J., Rosello, J., Nicholson, R. I., Mendelsohn, J., and Baselga, J. Activated extracellular signalregulated kinases: association with epidermal growth factor receptor/ transforming growth factor α expression in head and neck squamous carcinoma and inhibition by anti-epidermal growth factor receptor treatments. Cancer Res., 61: 6500-6510, 2001.
64. Stoll, S. W., Benedict, M., Mitra, R., Hiniker, A., Elder, J. T., and Nunez, G. EGF receptor signaling inhibits keratinocyte apoptosis: evidence for mediation by Bcl-XL. Oncogene, 16: 1493-1499, 1998.
65. Jost, M., Kari, C., and Rodeck, U. The EGF receptor - an essential regulator of multiple epidermal functions. Eur. J. Dermatol., 10: 505-510, 2000.
66. Hidalgo, M., Malik, S., Rowinsky, E., Miller, A., Duffey, D., de'Grafenreid, L., Siu, L., Simmons, C., Kreisberg, J., and Brattain, M. Inhibition of the epidermal growth factor receptor (EGFR) by OSI-774, a specific EGFR inhibitor in malignant and normal tissues of cancer patients. Proc. Am. Soc. Clin. Oncol. 20: 71a, 2001.
67. Hoekstra, R., Dumez, H., Eskens, F., Sizer, K., Cohen, P., Ravera, C., Verweij, J., and Van Oosterom, A. A Phase I and pharmacological study of intermittent dosing of PKII66, a novel epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, administered orally to patients with advanced cancer. Clin. Cancer Res., 7 (Suppl.): 3771s, 2001.
68. Zinner, R. G., Nemunaitis, J. J., Donato, N. J., Shin, H. C., Myers, J. N., Zhang, P. S., Zentgraft, R. E., Lee, J. J., Khuri, F. R., Glisson, B. S., et al. A Phase I clinical and biomarker study of the novel pan-erbB tyrosine kinase inhibitor, CI-1033, in patients with solid tumors. Clin. Cancer Res., 7 (Suppl.): 3767s, 2001.
69. Aboud-Pirak, E., Hurwitz, E., Pirak, M. E., Bellot, F., Schlessinger, J., and Sela, M. Efficacy of antibodies to epidermal growth factor receptor against KB carcinoma in vitro and in nude mice. J. Natl. Cancer Inst. (Bethesda), 80: 1605-1611, 1988.
70. Fan, Z., Baselga, J., Masui, H., and Mendelsohn, J. Antitumor effect of anti-epidermal growth factor receptor monoclonal antibodies plus cis-diamminedichloroplatinum on well-established A431 cell xenografts. Cancer Res., 53: 4637-4642, 1993.
71. Baselga, J., Norton, L., Masui, H., Pandiella, A., Coplan, K., Miller, W. H., Jr., and Mendelsohn, J. Antitumor effects of doxorubicin in combination with anti-epidermal growth factor receptor monoclonal antibodies. J. Natl. Cancer Inst. (Bethesda), 85: 1327-1333, 1993.
72. Huang, S. M., and Harari, P. M. Modulation of radiation response after epidermal growth factor receptor blockade in squamous cell carcinomas: inhibition of damage repair, cell cycle kinetics, and tumor angiogenesis. Clin. Cancer Res., 6: 2166-2174, 2000.
73. Simak, A., and Coombes, C. Endocrine-responsive breast cancer and strategies for combating resistance. Nat. Rev. Cancer, 22: 101-112, 2002.
74. Kurokawa, H., and Arteaga, C. L. Inhibition of erbB receptor (HER) tyrosine kinases as a strategy to abrogate antiestrogen resistance in human breast cancer. Clin. Cancer Res., 7 (Suppl.): 4436s-4442s, 2001.
75. Kurokawa, H., Lenferink, A. E., Simpson, J. F., Pisacane, P. I., Sliwkowski, M. X., Forbes, J. T., and Arteaga, C. L. Inhibition of HER2/neu (erbB-2) and mitogen-activated protein kinases enhances tamoxifen action against HER2-overexpressing, tamoxifen-resistant breast cancer cells. Cancer Res., 60: 5887-5894, 2000.
76. Witters, L. M., Kumar, R., Chinchilli, V. M., and Lipton, A. Enhanced anti-proliferative activity of the combination of tamoxifen plus HER-2-neu antibody. Breast Cancer Res. Treat., 42: 1-5, 1997.
77. Kunisue, H., Kurebayashi, J., Otsuki, T., Tang, C. K., Kurosumi, M., Yamamoto, S., Tanaka, K., Doihara, H., Shimizu, N., and Sonoo, H. Anti-HER2 antibody enhances the growth inhibitory effect of antioestrogen on breast cancer cells expressing both oestrogen receptors and HER2. Br. J. Cancer, 82: 46-51, 2000.
78. McClelland, R. A., Barrow, D., Madden, T. A., Dutkowski, C. M., Pamment, J., Knowlden, J. M., Gee, J. M., and Nicholson, R. I. Enhanced epidermal growth factor receptor signaling in MCF7 breast cancer cells after long-term culture in the presence of the pure antiestrogen ICI 182, 780 (Faslodex). Endocrinology, 142: 2776-2788, 2001.
79. Nicholson, R. I., Hutcheson, I. R., Harper, M. E., Knowlden, J. M., Barrow, D., McClelland, R. A., Jones, H. E., Wakeling, A. E., and Gee, J. M. Modulation of epidermal growth factor receptor in endocrineresistant, oestrogen receptor-positive breast cancer. Endocr.-Relat. Cancer, 8: 175-182, 2001.
80. Karunagaran, D., Tzahar, E., Beerli, R. R., Chen, X., Graus-Porta, D., Ratzkin, B. J., Seger, R., Hynes, N. E., and Yarden, Y. ErbB-2 is a common auxiliary subunit of NDF and EGF receptors: implications for breast cancer. EMBO J., 15: 254-264, 1996.
81. Muller, W. J., Arteaga, C. L., Muthuswamy, S. K., Siegel, P. M., Webster, M. A., Cardiff, R. D., Meise, K. S., Li, F., Halter, S. A., and Coffey, R. J. Synergistic interaction of the Neu proto-oncogene product and transforming growth factor α in the mammary epithelium of transgenic mice. Mol. Cell. Biol., 16: 5726-5736, 1996.
82. Tateishi, M., Ishida, T., Kohdono, S., Hamatake, M., Fukuyama, Y., and Sugimachi, K. Prognostic influence of the co-expression of epidermal growth factor receptor and c-erbB-2 protein in human lung adenocarcinoma. Surg. Oncol., 3: 109-113, 1994.
83. Xia, W., Lau, Y. K., Zhang, H. Z., Xiao, F. Y., Johnston, D. A., Liu, A. R., Li, L., Katz, R. L., and Hung, M. C. Combination of EGFR, HER-2/neu, and HER-3 is a stronger predictor for the outcome of oral squamous cell carcinoma than any individual family members. Clin. Cancer Res., 5: 4164-4174, 1999.
84. Nicholson, R. I., McClelland, R. A., Finlay, P., Eaton, C. L., Gullick, W. J., Dixon, A. R., Robertson, J. F., Ellis, I. O., and Blamey, R. W. Relationship between EGF-R, c-erbB-2 protein expression and Ki67 immunostaining in breast cancer and hormone sensitivity. Eur. J. Cancer, 7: 1018-1023, 1993.
85. Qian, X., Dougall, W. C., Hellman, M. E., and Greene, M. I. Kinase-deficient neu proteins suppress epidermal growth factor receptor function and abolish cell transformation. Oncogene, 9: 1507-1514, 1994.
86. Graus-Porta, D., Beerli, R. R., and Hynes, N. E. Single-chain antibody-mediated intracellular retention of ErbB-2 impairs Neu differentiation factor and epidermal growth factor signaling. Mol. Cell. Biol., 15: 1182-1191, 1995.
87. Christensen, J. G., Schreck, R. E., Chan, E., Wang, X., Yang, C., Liu, L., Cui, J., Sun, L., Wei, J., Cherrington, J. M., and Mendel, D. B. High levels of HER-2 expression alter the ability of epidermal growth factor receptor (EGFR) family tyrosine kinase inhibitors to inhibit EGFR phosphorylation in vivo. Clin. Cancer Res., 7: 4230-4238, 2001.
88. Lane, H. A., Beuvink, I., Motoyama, A. B., Daly, J. M., Neve, R. M., and Hynes, N. E. ErbB2 potentiates breast tumor proliferation through modulation of p27(Kip1)-Cdk2 complex formation: receptor overexpression does not determine growth dependency. Mol. Cell. Biol., 20: 3210-3223, 2000.
89. Motoyama, A. B., Hynes, N. E., and Lane, H. A. The efficacy of ErbB receptor-targeted anticancer therapeutics is influenced by the availability of epidermal growth factor-related peptides. Cancer Res., 62: 3151-3158, 2002.
90. Ye, D., Mendelsohn, J., and Fan, Z. Augmentation of a humanized anti-HER2 mAb 4D5 induced growth inhibition by a human-mouse chimeric anti-EGF receptor mAb C225. Oncogene, 18: 731-738, 1999.
91. Anderson, N. G., Ahmad, T., Chan, K., Dobson, R., and Bundred, N. J. ZD1839 (Iressa), a novel epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, potently inhibits the growth of EGFR- positive cancer cell lines with or without erbB2 overexpression. Int. J. Cancer, 94: 774-782, 2001.
92. Petit, A. M., Rak, J., Hung, M. C., Rockwell, P., Goldstein, N., Fendly, B., and Kerbel, R. S. 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. Am. J. Pathol., 151: 1523-1530, 1997.
93. Ciardiello, F., Caputo, R., Bianco, R., Damiano, V., Fontanini, G., Cuccato, S., De Placido, S., Bianco, A. R., and Tortora, G. Inhibition of growth factor production and angiogenesis in human cancer cells by ZD1839 (Iressa), a selective epidermal growth factor receptor tyrosine kinase inhibitor. Clin. Cancer Res., 7: 1459-1465, 2001.
94. Viloria-Petit, A., Crombet, T., Jothy, S., Hicklin, D., Bohlen, P., Schlaeppi, J. M., Rak, J., and Kerbel, R. S. Acquired resistance to the antitumor effect of epidermal growth factor receptor-blocking antibodies in vivo: a role for altered tumor angiogenesis. Cancer Res., 61: 5090-5101, 2001.
95. Chakravarti, A., Loeffler, J. S., and Dyson, N. J. Insulin-like growth factor receptor I mediates resistance to anti-epidermal growth factor receptor therapy in primary human glioblastoma cells through continued activation of phosphoinositide 3-kinase signaling. Cancer Res., 62: 200-207, 2002.
96. Lu, Y., Zi, X., Zhao, Y., Mascarenhas, D., and Pollak, M. Insulinlike growth factor-I receptor signaling and resistance to trastuzumab (Herceptin). J. Natl. Cancer Inst. (Bethesda), 93: 1852-1857, 2001.
97. Bianco, R., Shin, I., Ritter, C. A., Yakes, F. M., Basso, A., Rosen, N., Tsurutani, J., Dennis, P. A., Mills, G. B., and Arteaga, C. L. Loss of PTEN/MMAC1/TEP in EGF receptor-expressing tumor cells counteracts the antitumor action of EGFR tyrosine kinase inhibitors. Oncogene, 22: in press, 2003.
98. Moore, M., Winquist, E., Pollak, M., Chi, K., Berry, S., Ernst, S., Douglas, L., Baetz, T., Fisher, B., and Seymour, L. A randomised Phase II study of two doses of ZD1839 in patients (pts) with hormone refractory prostate cancer (HRPC): a NCI Canada Clinical Trials Group Study. Ann. Oncol., 13 (Suppl. 5): 90, 2002.
99. Seymour, L., Goss, G., Stewart, D., Hirte, H., Miller, W., Major, P., Batist, G., Matthews, S., Lorimer, I., and Douglass, L. A translational research study of ZD1839 at a dose of 750 mg in patients with pretreated advanced or metastatic colorectal cancer: NCIC CTG IND. 122. Ann. Oncol., 2002: 73, 2002.
100. Cohen, E. E., Hidalgo, M., Erlichman, C., Rowinsky, E. K., Koepp-Norris, J., Jensen, K., Boni, J., Korth-Bradley, J., Quinn, S., and Zacharchuk, C. Phase II study of ZD1839 (Iressa) in recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN). Proc. Am. Soc. Clin. Oncol., 21: 225a, 2002.
101. Townsley, C., Tabernero, J., Rojo, F., Jimenez, E., Montaner, I., Santome, L., Guix, M., Rosen, O., Kovar, A., Viaplana, I., and Baselga, J. Phase II study of OSI-774 in patients with metastatic colorectal cancer. Eur. J. Cancer, 38 (Suppl. 7): 69, 2002.
102. Senzer, N. N., Soulieres, D., Siu, L., Agarwala, S., Vokes, E., Hidalgo, M., Silberman, S., Allen, L., Ferrante, K., Fisher, D., Marsolais, C., and Nadler, P. Phase 2 evaluation of OSI-774, a potent oral antagonist of the EGFR-TK in patients with advanced squamous cell carcinoma of the head and neck. Proc. Am. Soc. Clin. Oncol., 20: 2a, 2001.
103. Finkler, N., Gordon, A., Crozier, M., Edwards, R., Figueroa, J., Garcia, A., Hainsworth, J., Irwin, D., Silberman, S., Allen, L., Ferrante, K., Fisher, D., and Nadler, P. Phase 2 evaluation of OSI-774, a potent oral antagonist of the EGFR-TK in patients with advanced ovarian carcinoma. Proc. Am. Soc. Clin. Oncol., 20: 208a, 2001.
104. Hidalgo, M., Wong, W. K., Arquette, M., Nabell, L., Needle, M. N., Waksal, H. W., and Herbst, R. S. Phase I trial of EKB-569, an irreversible inhibitor of the epidermal growth factor receptor (EGFR), in patients with advanced solid tumors. Proc. Am. Soc. Clin. Oncol. 21: 17a, 2002.
105. Hong, W. K., Kim, E. S., Mauer, A. M., Fossella, F. V., Jamison, T. A., Kies, M. S., Pisters, K. M., Glisson, B. S., Blumenschein, G. R., Zinner, R. G., Tran, H. T., Windt, P., Liu, D., Khuri, F., Dicke, K., Needle, M., Vokes, E. E., Hong, W. K., and Herbst, R. S. Efficacy and safety of the anti-epidermal growth factor antibody IMC-C225 in combination with cisplatin in patients with recurrent squamous cell carcinoma of the head and neck refractory to cisplatin containing chemotherapy. Proc. Am. Soc. Clin. Oncol., 20: 224a, 2001.
106. Kim, E. S., Mauer, A. M., Fossella, F. V., Jamison, T. A., Kies, M. S., Pisters, K. M., Glisson, B. S., Blumenschein, G. R., Zinner, R. G., Tran, H. T., Windt, P., Liu, D., Khuri, F., Dicke, K., Needle, M., Vokes, E. E., Hong, W. K., and Herbst, R. S. 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). Proc. Am. Soc. Clin. Oncol., 21: 293a, 2002.
107. Abbruzzese, J. L., Rosenberg, A., Xiong, Q., LoBuglio, A., Schmidt, W., Wolff, R., Needle, M., and Waksal, H. Phase II study of anti-epidermal growth factor receptor (EGFr) antibody cetuximab (IMC-C225) in combination with gemcitabine in patients with advanced pancreatic cancer. Proc. Am. Soc. Clin. Oncol., 20: 518, 2001.
108. Curnow, R. T. Clinical experience with CD64-directed immunotherapy. An overview. Cancer Immunol. Immunother., 45: 210-215, 1997.
109. Bier, H., Hoffmann, T., Hauser, U., Wink, M., Ochler, M., Kovar, A., Muser, M., and Knecht, R. Clinical trial with escalating doses of the antiepidermal growth factor receptor humanized monoclonal antibody EMD 72 000 in patients with advanced squamous cell carcinoma of the larynx and hypopharynx. Cancer Chemother. Pharmacol., 47: 519-524, 2001.
110. Townsley, C., Major, P., Siu, L. L., Dancey, J., Vincent, M., Pond, G., and MacLean, M. A Phase I pharmacokinetic (PK) and serial tumor and skin pharmacodynamic (PD) study of weekly, every 2 weeks or every 3 weeks 1-hour (h) infusion EMD72000, an humanized monoclonal anti-epidermal growth factor receptor (EGFR) antibody, in patients (p) with advanced tumors known to overexpress the EGFR. Eur. J. Cancer, 38 (Suppl. 7): 69, 2002.
111. Luwor, R. B., Johns, T. G., Murone, C., Huang, H. J., Cavenee, W. K., Ritter, G., Old, L. J., Burgess, A. W., and Scott, A. M. Monoclonal antibody 806 inhibits the growth of tumor xenografts expressing either the de2-7 or amplified epidermal growth factor receptor (EGFR) but not wild-type EGFR. Cancer Res., 61: 5355-5361, 2001.