Targeted therapy in colorectal cancer: Current status and future challenges

Current Medicinal Chemistry

Volumn 18, Issue 11, 2011, Pages 1599-1612

  Koutras, A K ^a   Starakis, I ^a   Kyriakopoulou, U ^a   Katsaounis, P ^a   Nikolakopoulos, A ^a   Kalofonos, H P ^a  

^a UNIVERSITY HOSPITAL OF PATRAS   (Greece)

Author keywords

Bevacizumab; Cetuximab; Colorectal cancer; Panitumumab; Targeted therapy

Indexed keywords

AFLIBERCEPT; BEVACIZUMAB; BIOLOGICAL MARKER; CAPECITABINE; CEDIRANIB; CETUXIMAB; EPIDERMAL GROWTH FACTOR RECEPTOR; FLUOROURACIL; FOLINIC ACID; GEFITINIB; IRINOTECAN; MOTESANIB; OXALIPLATIN; PANITUMUMAB; SORAFENIB; SUNITINIB; TIVOZANIB; VASCULOTROPIN; VATALANIB;

ANTINEOPLASTIC ACTIVITY; ARTICLE; BLEEDING; CANCER PATIENT; CARDIOMYOPATHY; CLINICAL PRACTICE; COLORECTAL CANCER; CONGESTIVE HEART FAILURE; DIARRHEA; DIGESTIVE SYSTEM PERFORATION; DISEASE FREE SURVIVAL; DRUG DOSE ESCALATION; DRUG EFFICACY; DRUG HYPERSENSITIVITY; DRUG SAFETY; DRUG TOLERABILITY; DRUG WITHDRAWAL; FOLLICULITIS; HUMAN; HYPERTENSION; HYPOMAGNESEMIA; LOADING DRUG DOSE; NONHUMAN; OVERALL SURVIVAL; POSTERIOR REVERSIBLE ENCEPHALOPATHY SYNDROME; PROGRESSION FREE SURVIVAL; PROTEINURIA; RASH; SKIN TOXICITY; THROMBOEMBOLISM; TREATMENT INDICATION; TREATMENT RESPONSE; WOUND HEALING IMPAIRMENT;

ANTINEOPLASTIC AGENTS; COLORECTAL NEOPLASMS; FORECASTING; HUMANS; MOLECULAR TARGETED THERAPY; NEOPLASM METASTASIS; RECEPTOR, EPIDERMAL GROWTH FACTOR; VASCULAR ENDOTHELIAL GROWTH FACTOR A;

EID: 79955677946     PISSN: 09298673     EISSN: None     Source Type: Journal    
DOI: 10.2174/092986711795471338     Document Type: Article

References (143)

1. Weitz, J.; Koch, M.; Debus, J.; Höhler, T.; Galle, P.R.; Büchler, M.W. Colorectal cancer. Lancet, 2005, 365, 153-165. (Pubitemid 40091806)
2. Yarden, Y.; Sliwkowski, M.X. Untangling the ErbB signalling network. Nat. Rev. Mol. Cell. Biol., 2001, 2, 127-137. (Pubitemid 33674041)
3. Scaltriti, M.; Baselga, J. The epidermal growth factor receptor pathway: a model for targeted therapy. Clin. Cancer. Res., 2006, 12, 5268-5272. (Pubitemid 44497237)
4. Koutras, A.; Evans, T.R. The epidermal growth factor receptor family in breast cancer. Onco. Targets Ther., 2008, 1, 5-19.
5. Klapper, L.N.; Kirschbaum, M.H.; Sela, M.; Yarden, Y. Biochemical and clinical implications of the ErbB/HER signaling network of growth factor receptors. Adv. Cancer Res., 2000, 77, 25-79. (Pubitemid 29439302)
6. Goldstein, N.S.; Armin, M. Epidermal growth factor receptor immunohistochemical reactivity in patients with American Joint Committee on Cancer Stage IV colon adenocarcinoma: Implications for a standardized scoring system. Cancer, 2001, 92, 1331-1346.
7. Spano, J.P.; Lagorce, C.; Atlan, D.; Milano, G.; Domont, J.; Benamouzig, R.; Attar, A.; Benichou, J.; Martin, A.; Morere, J.F.; Raphael, M.; Penault- Llorca, F.; Breau, J.L.; Fagard, R.; Khayat, D.; Wind, P. Impact of EGFR expression on colorectal cancer patient prognosis and survival. Ann. Oncol., 2005, 16, 102-108. (Pubitemid 40124486)
8. Zlobec, I.; Vuong, T.; Hayashi, S.; Haegert, D.; Tornillo, L.; Terracciano, L.; Lugli, A.; Jass, J. A simple and reproducible scoring system for EGFR in colorectal cancer: Application to prognosis and prediction of response to preoperative brachytherapy. Br. J. Cancer, 2007, 96, 793-800. (Pubitemid 46376624)
9. Viloria-Petit, A.M.; Kerbel, R.S. Acquired resistance to EGFR inhibitors: Mechanisms and prevention strategies. Int. J. Radiat. Oncol. Biol. Phys., 2004, 58, 914-926. (Pubitemid 38221151)
10. De Roock, W.; Piessevaux, H.; De Schutter, J.; Janssens, M.; De Hertogh, G.; Personeni, N.; Biesmans, B.; Van Laethem, J.L.; Peeters, M.; Humblet, Y.; Van Cutsem, E.; Tejpar, S. KRAS wild-type state predicts survival and is associated to early radiological response in metastatic colorectal cancer treated with cetuximab. Ann. Oncol., 2008, 19, 508-515. (Pubitemid 351325672)
11. Di Fiore, F.; Blanchard, F.; Charbonnier, F.; Le Pessot, F.; Lamy, A.; Galais, M.P.; Bastit, L.; Killian, A.; Sesboüé, R.; Tuech, J.J.; Queuniet, A.M.; Paillot, B.; Sabourin, J.C.; Michot, F.; Michel, P.; Frebourg, T. Clinical relevance of KRAS mutation detection in metastatic colorectal cancer treated by Cetuximab plus chemotherapy. Br. J. Cancer., 2007, 96, 1166-1169. (Pubitemid 46625066)
12. Lièvre, A.; Bachet, J.B.; Boige, V.; Cayre, A.; Le Corre, D.; Buc, E.; Ychou, M.; Bouché, O.; Landi, B.; Louvet, C.; André, T.; Bibeau, F.; Diebold, M.D.; Rougier, P.; Ducreux, M.; Tomasic, G.; Emile, J.F.; Penault-Llorca, F.; Laurent-Puig, P. KRAS mutations as an independent prognostic factor in patients with advanced colorectal cancer treated with cetuximab. J. Clin. Oncol., 2008, 26, 374-379. (Pubitemid 351171687)
13. Garm Spindler, K.L.; Pallisgaard, N.; Rasmussen, A.A.; Lindebjerg, J.; Andersen, R.F.; Crüger, D.; Jakobsen, A. The importance of KRAS mutations and EGF61A>G polymorphism to the effect of cetuximab and irinotecan in metastatic colorectal cancer. Ann Oncol., 2009, 20, 879-884.
14. Loupakis, F.; Pollina, L.; Stasi, I.; Ruzzo, A.; Scartozzi, M.; Santini, D.; Masi, G.; Graziano, F.; Cremolini, C.; Rulli, E.; Canestrari, E.; Funel, N.; Schiavon, G.; Petrini, I.; Magnani, M.; Tonini, G.; Campani, D.; Floriani, I.; Cascinu, S.; Falcone, A. PTEN expression and KRAS mutations on primary tumors and metastases in the prediction of benefit from cetuximab plus irinotecan for patients with metastatic colorectal cancer. J. Clin. Oncol., 2009, 27, 2622-2629.
15. Goldstein, N.I.; Prewett, M. Biological efficacy of a chimeric antibody to the epidermal growth factor receptor in a human tumor xenograft model. Clin. Cancer Res., 1995, 1, 1311-1318.
16. Humblet, Y. Cetuximab: an IgG1 monoclonal antibody for the treatment of epidermal growth factor receptor-expressing tumors. Expert Opin. Pharmacother., 2004, 5, 1621-1633. (Pubitemid 39029042)
17. Wu, X.; Fan, Z.; Masui, H.; Rosen, N.; 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. Invest., 1995, 95, 1897-1905.
18. Peng, D.; Fan, Z.; Lu, Y.; DeBlasio, T.; Scher, H.; Mendelsohn, J. Antiepidermal growth factor receptor monoclonal antibody 225 upregulates p27KIP1 and induces G1 arrest in prostatic cancer cell line DU145. Cancer Res., 1996, 56, 3666-3669. (Pubitemid 26272010)
19. Perrotte, P.; Matsumoto, T.; Inoue, K.; Kuniyasu, H.; Eve, B.Y.; Hicklin, D.J.; Radinsky, R.; Dinney, C.P. Anti-epidermal growth factor receptor antibody C225 inhibits angiogenesis in human transitional cell carcinoma growing orthotopically in nude mice. Clin. Cancer Res., 1999, 5, 257-265. (Pubitemid 29085177)
20. Liu, B.; Fang, M.; Lu, Y.; Mendelsohn, J.; Fan, Z. Fibroblast growth factor and insulin-like growth factor differentially modulate the apoptosis and G1 arrest induced by anti-epidermal growth factor receptor monoclonal antibody. Oncogene, 2001, 20, 1913-1922. (Pubitemid 32458701)
21. Ciardiello, F.; Bianco, R.; Damiano, V.; De Lorenzo, S.; Pepe, S.; De Placido, S.; Fan, Z.; Mendelsohn, J.; Bianco, A.R.; Tortora, G. Antitumor activity of sequential treatment with topotecan and anti-epidermal growth factor receptor monoclonal antibody C225. Clin. Cancer Res., 1999, 5, 909-916. (Pubitemid 29180844)
22. 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.; Mendelsohn, J. Phase I studies of anti- epidermal growth factor receptor chimeric antibody C225 alone and in combinationwith cisplatin. J. Clin. Oncol., 2000, 18, 904.
23. Robert, F.; Ezekiel, M.P.; Spencer, S.A.; Meredith, R.F.; Bonner, J.A.; Khazaeli, M.B.; Saleh, M.N.; Carey, D.; LoBuglio, A.F.; Wheeler, R.H.; Cooper, M.R.; Waksal, H.W. Phase I study of anti-epidermal growth factor receptor antibody cetuximab in combinationwith radiation therapy in patients with advanced head and neck cancer. J. Clin. Oncol., 2001, 19, 3234-3243. (Pubitemid 32591441)
24. Reynolds, N.A.; Wagstaff, A.J. Cetuximab in the treatment of metastatic colorectal cancer. Drugs, 2004, 64, 109-118. (Pubitemid 38125631)
25. ImClone Systems Inc, Bristol-Myers Squibb. Erbitux (cetuximab) package insert. New York, NY, and Princeton, NJ; 2006.
26. Lobo, E.D.; Hansen, R.J.; Balthasar, J.P. Antibody pharmacokinetics and pharmacodynamics. J. Pharm. Sci., 2004, 93, 2645-2668. (Pubitemid 39506617)
27. Ettlinger, D.E.; Mitterhauser, M.; Wadsak, W.; Ostermann, E.; Farkouh, A.; Schueller, J.; Czejka, M. In vivo disposition of irinotecan (cpt-11) and its metabolites in combination with the monoclonal antibody cetuximab. Anticancer Res., 2006, 26, 1337-1342.
28. Tabernero, J.; Cervantes, A.; Martinelli, E.; Vega-Villegas, E.; Rojo, F.; Pérez-Fidalgo, A.; Casado, E.; Ciardiello, F.; Zubel, A.; Baselga, J. In: Optimal dose of cetuximab (C) given every 2 weeks (q2w): A phase I pharmacokinetic (PK) and pharmacodynamic (PD) study of weekly (q1w) and q2w schedules in patients (pts) with metastatic colorectal cancer (mCRC), Proceedings of the 2006 American Society of Clinical Oncology Annual Meeting, Atlanta, Georgia, June 2-6, 2006; Journal of Clinical Oncology: 2006; Abstr 3085.
29. Liang, K.; Ang, K.K.; Milas, L.; Hunter, N.; Fan, Z. The epidermal growth factor receptor mediates radioresistance. Int. J. Radiat. Oncol. Biol. Phys., 2003, 57, 246-254. (Pubitemid 36959763)
30. Dittmann, K.; Mayer, C.; Rodemann, H.P. Inhibition of radiation-induced EGFR nuclear import by C225 (cetuximab) suppresses DNA-PK activity. Radiother. Oncol., 2005, 76(2), 157-161. (Pubitemid 41725442)
31. Schmidt-Ullrich, R.K.; Mikkelsen, R.B.; Dent, P.; Todd, D.G.; Valerie, K.; Kavanagh, B.D.; Contessa, J.N.; Rorrer, W.K.; Chen, P.B. Radiation-induced proliferation of the human A431 squamous carcinoma cells is dependent on EGFR tyrosine phosphorylation. Oncogene, 1997, 15(10), 1191-1197. (Pubitemid 27429622)
32. Dent. P.; Reardon, D.; Park, J.S.; Bowers, G.; Logsdon, C.; Valerie, K.; Schmidt-Ullrich, R. Radiation-induced Release of Transforming Growth Factor - Activates the Epidermal Growth Factor Receptor and Mitogenactivated Protein Kinase Pathway in Carcinoma Cells, Leading to Increased Proliferation and Protection from Radiation-induced Cell Death. Mol. Biol. Cell., 1999, 10(8), 2493-2506.
33. Gorski, D.H.; Beckett, M.A.; Jaskowiak, N.T.; Calvin, D.P.; Mauceri, H.J.; Salloum, R.M.; Seetharam, S.; Koons, A.; Hari, D.M.; Kufe, D.W.; Weichselbaum, R.R. Blockage of the vascular endothelial growth factor stress response increases the antitumor effects of ionizing radiation. Cancer Res., 1999, 59(14), 3374-3378. (Pubitemid 29334495)
34. Hess, C.; Vuong, V.; Hegyi, I.; Riesterer, O.; Wood, J.; Fabbro, D.; Glanzmann, C.; Bodis. S.; Pruschy, M. Effect of VEGF receptor inhibitor PTK787/ZK222584 [correction of ZK222548] combined with ionizing radiation on endothelial cells and tumour growth. Br. J. Cancer, 2001, 85(12), 2010-2016. (Pubitemid 34775341)
35. Zips, D.; Eicheler, W.; Geyer, P.; Hessel, F.; Dörfler, A.; Thames, H.D.; Haberey, M.; Baumann, M. Enhanced susceptibility of irradiated tumor vessels to vascular endothelial growth factor receptor tyrosine kinase inhibition. Cancer Res., 2005, 65(12), 5374-5379. (Pubitemid 40827351)
36. Pueyo, G.; Mesia, R.; Figueras, A.; Lozano, A.; Baro, M.; Vazquez, S.; Capella, G.; Balart, J. Cetuximab may inhibit tumor growth and angiogenesis induced by ionizing radiation: a preclinical rationale for maintenance treatment after radiotherapy. Oncologist, 2010, 15(9), 976-986.
37. Benhar, M.; Engelberg, D.; Levitzki, A. Cisplatin-induced activation of the EGF receptor. Oncogene, 2002, 21, 8723-8731. (Pubitemid 36132393)
38. Van Schaeybroeck, S.; Karaiskou-McCaul, A.; Kelly, D.; Longley, D.; Galligan, L.; Van Cutsem, E.; Johnston, P. Epidermal growth factor receptor activity determines response of colorectal cancer cells to gefitinib alone and in combination with chemotherapy. Clin. Cancer Res., 2005, 11, 7480-7489. (Pubitemid 41507709)
39. Sumitomo, M.; Asano, T.; Asakuma, J.; Asano, T.; Horiguchi, A.; Hayakawa, M. ZD1839 modulates paclitaxel response in renal cancer by blocking paclitaxel-induced activation of the epidermal growth factor receptor-extracellular signal-regulated kinase pathway. Clin. Cancer Res., 2004, 10, 794-801. (Pubitemid 38174018)
40. Prewett, M.C.; Hooper, A.T.; Bassi, R.; Ellis, L.M.; Waksal, H.W.; 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., 2002, 8, 994-1003. (Pubitemid 34517632)
41. Saltz, L.B.; Meropol, N.J.; Loehrer, P.J. Sr.; Needle, M.N.; Kopit, J.; Mayer, R.J. Phase II trial of cetuximab in patients with refractory colorectal cancer that expresses the epidermal growth factor receptor. J. Clin. Oncol., 2004, 22, 1201-1208. (Pubitemid 41079832)
42. Cunningham, D.; Humblet, Y.; Siena, S.; Khayat, D.; Bleiberg, H.; Santoro, A.; Bets, D.; Mueser, M.; Harstrick, A.; Verslype, C.; Chau, I.; Van Cutsem, E. Cetuximab monotherapy and cetuximab plus irinotecan in irinotecanrefractory metastatic colorectal cancer. N. Engl. J. Med., 2004, 351, 337-345. (Pubitemid 38944402)
43. Lenz, H.J.; Mayer, R.J.; Gold, P.J.; Mirtsching, B.; Stella, P.J.; Cohn, A.L.; Pippas, A.W.; Azarnia, N.; Needle, M.N.; Van Cutsem, E. In: Activity of cetuximab in patients with colorectal cancer refractory to both irinotecan and oxaliplatin, Proceedings of the 2004 American Society of Clinical Oncology Annual Meeting, New Orleans, Louisiana, June 5-8, 2004; Journal of Clinical Oncology: 2004; Abstr 3510.
44. Wilke, H.; Glynne-Jones, R.; Thaler, J.; Adenis, A.; Preusser, P.; Aranda Aguilar, E.; Aapro, M.; Van Den Berg, N.; Eggleton, S.; Siena, S. In: MABEL: A large multinational study of cetuximab plus irinotecan in irinotecan resistant metastatic colorectal cancer, Proceedings of the 2006 American Society of Clinical Oncology Annual Meeting, Atlanta, Georgia, June 2-6, 2006; Journal of Clinical Oncology: 2006; Abstr 3549.
45. Tejpar, S.; Peeters, M.; Humblet, Y.; Gelderblom, H.; Vermorken, J.; Viret, F.; Glimelius, B.; Ciardiello, F.; Kisker, O.; Van Cutsem, E. In: Phase I/II study of cetuximab dose-escalation in patients with metastatic colorectal cancer (mCRC) with no or slight skin reactions on cetuximab standard dose treatment (EVEREST): Pharmacokinetic (PK), Pharmacodynamic (PD) and efficacy data, Proceedings of the 2007 American Society of Clinical Oncology Annual Meeting, Chicago, Illinois, June 1-5, 2007; Journal of Clinical Oncology: 2007; Abstr 4037.
46. Jonker, D.J.; O'Callaghan, C.J.; Karapetis, C.S.; Zalcberg, J.R.; Tu, D.; Au, H.J.; Berry, S.R.; Krahn, M.; Price, T.; Simes, R.J.; Tebbutt, N.C.; van Hazel, G.; Wierzbicki, R.; Langer, C.; Moore, M.J. Cetuximab for the treatment of colorectal cancer. N. Engl. J. Med., 2007, 357(20), 2040-2048. (Pubitemid 350106711)
47. Jennis, A.; Polikoff, J.; Mitchell, E.; Badarinath, S.; Graham, C.; Chen, T.; Gustafson, T.; Langer, C. In: Erbitux (Cetuximab) Plus FOLFOX for Colorectal Cancer (EXPLORE): Preliminary efficacy analysis of a randomized phase III trial, Proceedings of the 2005 American Society of Clinical Oncology Annual Meeting, Orlando, Florida, May 13-17, 2005; Journal of Clinical Oncology: 2005; Abstr 3574.
48. Sobrero, A.F.; Maurel, J.; Fehrenbacher, L.; Scheithauer, W.; Abubakr, Y.A.; Lutz, M.P.; Vega-Villegas, M.E.; Eng, C.; Steinhauer, E.U.; Prausova, J.; Lenz, H.J.; Borg, C.; Middleton, G.; Kröning, H.; Luppi, G.; Kisker, O.; Zubel, A.; Langer, C.; Kopit, J.; Burris, H.A.3rd. EPIC: phase III trial of cetuximab plus irinotecan after fluoropyrimidine and oxaliplatin failure in patients with metastatic colorectal cancer. J. Clin. Oncol., 2008, 26, 2311-2319.
49. Rougier, P.; Raoul, J.L.; Van Laethem, J.L.; Peeters, M.; Husseini, F.; Brezault, C.; Cals, L.; Vedovato, J.C.; Mueser, M. In: Cetuximab+FOLFIRI as first-line treatment for metastatic colorectal cancer, Proceedings of the 2004 American Society of Clinical Oncology Annual Meeting, New Orleans, Louisiana, June 5-8, 2004; Journal of Clinical Oncology: 2004; Abstr 3513.
50. Rosenberg, A.H.; Loehrer, P.J.; Needle, M.N.; Waksal, H.; Hollywood, E.; Ramos, L.; Saltz, L.B. In: 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 2002 American Society of Clinical Oncology Annual Meeting, Orlando, Florida., May 18-21, 2002; Abstr 536.
51. Folprecht, G.; Lutz, M.P.; Schöffski, P.; Seufferlein, T.; Nolting, A.; Pollert, P.; Köhne, C.H. Cetuximab and irinotecan/5-fluorouracil/ folinic acid is a safe combination for the first-line treatment of patients with epidermal growth factor receptor expressing metastatic colorectal carcinoma. Ann. Oncol., 2006, 17, 450-456. (Pubitemid 43329582)
52. Seufferlein, T.; Dittrich, C.; Riemann, J.; Woell, E.; Herrmann, T.; Lordick, F.; Arnold, D.; Olchowka, K.; Hoehler, T.; Schmoll, H.J. In: A phase I/II study of cetuximab in combination with 5-fluorouracil (5-FU)/folinic acid (FA) plus weekly oxaliplatin (L-OHP) (FUFOX) in the first-line treatment of patients with metastatic colorectal cancer (mCRC) expressing epidermal growth factor receptor (EGFR).Preliminary Results, Proceedings of the 2005 American Society of Clinical Oncology Annual Meeting, Orlando, Florida, May 13-17, 2005; Journal of Clinical Oncology: 2005; Abstr 3644.
53. Díaz Rubio, E.; Tabernero, J.; van Cutsem, E.; Cervantes, A.; André, T.; Humblet, Y.; Soulié, P.; Corretgé, S.; Kisker, O.; de Gramont, A. In: Cetuximab in combination with oxaliplatin/5-fluorouracil (5-FU)/folinic acid (FA) (FOLFOX-4) in the first-line treatment of patients with epidermal growth factor receptor (EGFR)-expressing metastatic colorectal cancer: An international phase II study, Proceedings of the 2005 American Society of Clinical Oncology Annual Meeting, Orlando, Florida, May 13-17, 2005; Journal of Clinical Oncology: 2005; Abstr 3535.
54. Venook, A.; Niedzwiecki, D.; Hollis, D.; Sutherland, S.; Goldberg, R.; Alberts, S.; Benson, A.; Wade, J.; Schilsky, R.; Mayer, R. In: Phase III study of irinotecan/5FU/LV (FOLFIRI) or oxaliplatin/5FU/LV (FOLFOX)±cetuximab for patients (pts) with untreated metastatic adenocarcinoma of the colon or rectum (MCRC): CALGB 80203 preliminary results, Proceedings of the 2006 American Society of Clinical Oncology Annual Meeting, Atlanta, Georgia, June 2-6, 2006; Journal of Clinical Oncology: 2006; Abstr 3509.
55. Bokemeyer, C.; Bondarenko, I.; Makhson, A.; Hartmann, J.T.; Aparicio, J.; de Braud, F.; Donea, S.; Ludwig, H.; Schuch, G.; Stroh, C.; Loos, A.H.; Zubel, A.; Koralewski, P. Fluorouracil, leucovorin, and oxaliplatin with and without cetuximab in the first-line treatment of metastatic colorectal cancer. J. Clin. Oncol., 2009, 27, 663-671.
56. Van Cutsem, E.; Köhne, C.H.; Hitre, E.; Zaluski, J.; Chang Chien, C.R.; Makhson, A.; D'Haens, G.; Pintér, T.; Lim, R.; Bodoky, G.; Roh, J.K.; Folprecht, G.; Ruff, P.; Stroh, C.; Tejpar, S.; Schlichting, M.; Nippgen, J.; Rougier, P. Cetuximab and chemotherapy as initial treatment for metastatic colorectal cancer. N. Engl. J. Med., 2009, 360, 1408-1417.
57. Van Cutsem, E.; Rougier, P.; Köhne, C.; Stroh, C.; Schlichting, M.; Bokemeyer, C. In: A meta-analysis of the CRYSTAL and OPUS studies combining cetuximab with chemotherapy (CT) as 1st-line treatment for patients (pts) with metastatic colorectal cancer (mCRC): results according to KRAS and BRAF mutation status, Proceedings of the Joint European Cancer Organisation 15 - 34th European Society for Medical Oncology Multidisciplinary Congress, Berlin, Germany, September 20-24, 2009; European Journal of Cancer Supplements: 2009; Abstr 6077.
58. Maughan, T.; Adams, R.A.; Smith, C.G.; Seymour, M.T.; Wilson, R.; Meade, A.M.; Fisher, D.; Madi, A.; Cheadle, J.; Kaplan, R. In: Addition of cetuximab to oxaliplatin-based combination chemotherapy (CT) in patients with KRAS wild-type advanced colorectal cancer (ACRC): a randomised superiority trial (MRC COIN), Proceedings of the Joint European Cancer Organisation 15 - 34th European Society for Medical Oncology Multidisciplinary Congress, Berlin, Germany, September 20-24, 2009; European Journal of Cancer Supplements: 2009; Abstr 6LBA.
59. Goldberg, R.M.; Sargent, D.J.; Thibodeau, S.N.; Mahoney, M.R.; Shields, A.F.; Chan, E.; Gill, S.; Kahlenberg, M.S.; Nair, S.; Alberts, S.R. In: Adjuvant mFOLFOX6 plus or minus cetuximab (Cmab) in patients (pts) with KRAS mutant (m) resected stage III colon cancer (CC): NCCTG Intergroup Phase III Trial N0147, Proceedings of the 2010 American Society of Clinical Oncology Annual Meeting, Chicago, Illinois, June 4-8, 2010; Journal of Clinical Oncology: 2010; Abstr 3508.
60. Folprecht, G.; Gruenberger, T.; Hartmann, J.T.; Lordick, F.; Stoehlmacher, J.; Bechstein, W.O.; Ockert, D.; Herrmann, T.; Liersch, T.; Köhne, C.H. In: Cetuximab plus FOLFOX6 or cetuximab plus FOLFIRI as neoadjuvant treatment of nonresectable colorectal liver metastases: A randomized multicenter study (CELIM-study), Proceedings of the 2009 American Society of Clinical Oncology Gastrointestinal Cancers Symposium, San Fransisco, California, January 15-17, 2009; Abstr 296.
61. Garufi, C.; Torsello, A.; Tumolo, S.; Mottolese, M.; Campanella, C.; Zeuli, M.; Lo Re, G.; Sperduti, I.; Pizzi, G.; Ettorre, G.M. In: POCHER (preoperative chemotherapy for hepatic resection) with cetuximab (Cmab) plus CPT-11/5-fluorouracil (5-FU)/leucovorin(FA)/oxaliplatin (L-OHP) (CPT-11-FFL) in unresectable colorectal liver metastases (CLM), Proceedings of the 2009 American Society of Clinical Oncology Annual Meeting, Orlando, Florida, May 29-June 2, 2009; Journal of Clinical Oncology: 2009; Abstr e15020.
62. Yang, X.D.; Jia, X.C.; Corvalan, J.R.; Wang, P.; Davis, C.G.; Jakobovits, A. Eradication of established tumors by a fully human monoclonal antibody to the epidermal growth factor receptor without concomitant chemotherapy. Cancer Res., 1999, 59, 1236-1243. (Pubitemid 29136253)
63. Freeman, D.; McDorman, K.; Bush, T.; Starnes, C.; Cerretti, D.; Yang, X.; Leal, L.; Radinsky, R. In: Mono- and combination-therapeutic activity of panitumumab (ABX-EGF) on human A431 epidermoid and HT-29 colon carcinoma xenografts; correlation with pharmacodynamic parameters, Proceedings of the American Association for Cancer Research Annual Meeting, Orlando, Florida, March 27-31, 2004; European Journal of Cancer Supplements: 2004; Abstr 313.
64. Foon, K.A.; Yang, X.D.; Weiner, L.M.; Belldegrun, A.S.; Figlin, R.A.; Crawford, J.; Rowinsky, E.K.; Dutcher, J.P.; Vogelzang, N.J.; Gollub, J.; Thompson, J.A.; Schwartz, G.; Bukowski, R.M.; Roskos, L.K.; Schwab, G.M. Preclinical and clinical evaluations of ABX-EGF, a fully human antiepidermal growth factor receptor antibody. Int. J. Radiat. Oncol. Biol. Phys., 2004, 58, 984-990. (Pubitemid 38221160)
65. Rowinsky, E.K.; Schwartz, G.H.; Gollob, J.A.; Thompson, J.A.; Vogelzang, N.J.; Figlin, R.; Bukowski, R.; Haas, N.; Lockbaum, P.; Li, Y.P.; Arends, R.; Foon, K.A.; Schwab, G.; Dutcher, J. Safety, pharmacokinetics, and activity of ABX-EGF, a fully human anti-epidermal growth factor receptor monoclonal antibody in patients with metastatic renal cell cancer. J. Clin. Oncol., 2004, 22, 3003-3015. (Pubitemid 41103711)
66. Weiner, L.M.; Belldegrun, A.S.; Crawford, J.; Tolcher, A.W.; Lockbaum, P.; Arends, R.H.; Navale, L.; Amado, R.G.; Schwab, G.; Figlin, R.A. Dose and schedule study of panitumumab monotherapy in patients with advanced solid malignancies. Clin. Cancer Res., 2008, 14, 502-508 (Pubitemid 351226119)
67. Anon.Summary of Product Characteristics, available at: http://www.emea.europa.eu/humandocs/PDFs/EPAR/vectibix/ H-741-PIen. pdf (Accessed 10 March, 2008).
68. Helbling, D.; Borner, M. Successful challenge with the fully human EGFR antibody panitumumab following an infusion reaction with the chimeric EGFR antibody cetuximab. Ann. Oncol., 2007, 18, 963-964. (Pubitemid 47054100)
69. Langerak, A.D.; Mitchell, E.; Cheema, P.; River, G.L.; Shing, M. In: Institutional experiences with panitumumab monotherapy in metastatic colorectal cancer (mCRC) patients (pts) intolerant to cetuximab, Proceedings of the 2007 American Society of Clinical Oncology Annual Meeting, Chicago, Illinois, June 1-5, 2007; Journal of Clinical Oncology: 2007; Abstr 14579.
70. Heun, J.; Holen, K. Treatment with panitumumab after a severe infusion reaction to cetuximab in a patient with metastatic colorectal cancer: a case report. Clin. Colorectal Cancer, 2007, 6, 529-531. (Pubitemid 46918159)
71. Asmis, T.; Shah, M.; Haviland, D.; Kemeny, N. In: Panitumumab with or without chemotherapy in metastatic colorectal cancer (mCRC): safety and unusual activity, even following progression on cetuximab, Proceedings of the 2008 American Society of Clinical Oncology Gastrointestinal Cancers Symposium, Orlando, Florida, January 25-27, 2008; Abstr 484.
72. Hendlisz, A.; Van Cutsem, E.; Peeters, M.; Siena, S.; Humblet, Y.; Neyns, B.; Canon, J.L.; Van Laethem, J.L.; Maurel, J.; Richardson, Gary. In: Treatment effect of panitumumab by skin toxicity severity: results from a phase 3 randomized controlled trial, Proceedings of the 31st European Society for Medical Oncology Congress, Istanbul, Turkey, September 29 - October 3, 2006; Annals of Oncology: 2006; Abstr 983PD.
73. Hecht, J.R.; Patnaik, A.; Berlin, J.; Venook, A.; Malik, I.; Tchekmedyian, S.; Navale, L.; Amado, R.G.; Meropol, N.J. Panitumumab monotherapy in patients with previously treated metastatic colorectal cancer. Cancer, 2007, 110, 980-988. (Pubitemid 47312862)
74. Berlin, J.; Neubauer, M.; Swanson, P.; Harker, W.G.; Burris, H.; Hecht, J.R.; Navale, L. In: Panitumumab antitumor activity in patients (pts) with metastatic colorectal cancer (mCRC) expressing >=10% epidermal growth factor receptor (EGFr), Proceedings of the 2006 American Society of Clinical Oncology Annual Meeting, Atlanta, Georgia, June 2-6, 2006; Journal of Clinical Oncology: 2006; Abstr 3548.
75. Yoshino, T.; Muro, K.; Doi, T.; Shirao, K.; Takiuchi, H.; Hamamoto, Y.; Ohkura, M.; Asahi, D.; Ohtsu, T. In: Phase II study of panitumumab (Pmab) monotherapy in Japanese patients (pts) with metastatic colorectal cancer (mCRC) after the failure of fluoropyrimidine, irinotecan (CPT-11), and oxaliplatin (OHP) chemotherapy, Proceedings of the 2008 American Society of Clinical Oncology Gastrointestinal Cancers Symposium, Orlando, Florida, January 25-27, 2008; Abstr 366.
76. Van Cutsem, E.; Peeters, M.; Siena, S.; Humblet, Y.; Hendlisz, A.; Neyns, B.; Canon, J.L.; Van Laethem, J.L.; Maurel, J.; Richardson, G.; Wolf, M.; Amado, R.G. Open-label phase III trial of panitumumab plus best supportive care compared with best supportive care alone in patients with chemotherapy- refractory metastatic colorectal cancer. J. Clin. Oncol., 2007, 25, 1658-1664. (Pubitemid 46797944)
77. Amado, R.G.; Wolf, M.; Peeters, M.; Van Cutsem, E.; Siena, S.; Freeman, D.J.; Juan, T.; Sikorski, R.; Suggs, S.; Radinsky, R.; Patterson, S.D.; Chang, D.D. Wild-type KRAS is required for panitumumab efficacy in patients with metastatic colorectal cancer. J. Clin. Oncol., 2008, 26, 1626-1634.
78. Douillard, J.; Siena, S.; Cassidy, J.; Tabernero, J.; Burkes, R.; Barugel, M.E.; Humblet, Y.; Cunningham, D.; Wolf, M.; Gansert, J.L. In: Randomized phase 3 study of panitumumab with FOLFOX4 compared to FOLFOX4 alone as 1st-line treatment (tx) for metastatic colorectal cancer (mCRC): the PRIME trial, Proceedings of the Joint European Cancer Organisation 15 - 34th European Society for Medical Oncology Multidisciplinary Congress, Berlin, Germany, September 20-24, 2009; European Journal of Cancer Supplements: 2009; Abstr 10LBA.
79. Peeters, M.; Price, T.; Hotko, Y.; Cervantes, A.; Ducreux, M.; André, T.; Chan, E.; Lordick, F.; Rong, A.; Gansert, J. In: Randomized phase 3 study of panitumumab with FOLFIRI vs. FOLFIRI alone as second-line treatment (tx) in patients (pts) with metastatic colorectal cancer (mCRC), Proceedings of the Joint European Cancer Organisation 15 - 34th European Society for Medical Oncology Multidisciplinary Congress, Berlin, Germany, September 20-24, 2009; European Journal of Cancer Supplements: 2009; Abstr 14LBA.
80. Rothenberg, M.L.; LaFleur, B.; Levy, D.E.; Washington, M.K.; Morgan- Meadows, S.L.; Ramanathan, R.K.; Berlin, J.D.; Benson, A.B. 3rd.; Coffey, R.J. Randomized phase II trial of the clinical and biological effects of two dose levels of gefitinib in patients with recurrent colorectal adenocarcinoma. J. Clin. Oncol., 2005, 23, 9265-9274.
81. Santoro, A.; Comandone, A.; Rimassa, L.; Granetti, C.; Lorusso, V.; Oliva, C.; Ronzoni, M.; Siena, S.; Zuradelli, M.; Mari, E.; Pressiani, T.; Carnaghi, C. A phase II randomized multicenter trial of gefitinib plus FOLFIRI and FOLFIRI alone in patients with metastatic colorectal cancer. Ann. Oncol., 2008, 19, 1888-1893.
82. Barber, T.D.; Vogelstein, B.; Kinzler, K.W.; Velculescu, V.E. Somatic mutations of EGFR in colorectal cancers and glioblastomas. N. Engl. J. Med., 2004, 351, 2883. (Pubitemid 40051921)
83. Baselga, J.; Schöffski, P.; Rojo, F.; Dumez, H.; Ramos, F.J.; Macarulla, T.; Cajal, R.; Kisker, O.; Van Oosterom, A.; Tabernero, J. In: A phase I pharmacokinetic (PK) and molecular pharmacodynamic (PD) study of the combination of two anti-EGFR therapies, the monoclonal antibody (MAb) cetuximab (C) and the tyrosine kinase inhibitor (TKI) gefitinib (G), in patients (pts) with advanced colorectal (CRC), head and neck (HNC) and non-small cell lung cancer (NSCLC), Proceedings of the 2006 American Society of Clinical Oncology Annual Meeting, Atlanta, Georgia, June 2-6, 2006; Journal of Clinical Oncology: 2006; Abstr 3006.
84. Andreyev, H.J.; Norman, A.R.; Cunningham, D.; Oates, J.R.; Clarke, P.A.. Kirsten ras mutations in patients with colorectal cancer: The multicenter "RASCAL" study. J. Natl. Cancer Inst., 1998, 90, 675-684. (Pubitemid 28222141)
85. Oliveira, C.; Westra, J.L.; Arango, D.; Ollikainen, M.; Domingo, E.; Ferreira, A.; Velho, S.; Niessen, R.; Lagerstedt, K.; Alhopuro, P.; Laiho, P.; Veiga, I.; Teixeira, M.R.; Ligtenberg, M.; Kleibeuker, J.H.; Sijmons, R.H.; Plukker, J.T.; Imai, K.; Lage, P.; Hamelin, R.; Albuquerque, C.; Schwartz, S. Jr.; Lindblom, A.; Peltomaki, P.; Yamamoto, H.; Aaltonen, L.A.; Seruca, R.; Hofstra, R.M. Distinct patterns of KRAS mutations in colorectal carcinomas according to germline mismatch repair defects and hMLH1 methylation status. Hum. Mol. Genet., 2004, 13, 2303-2311. (Pubitemid 39359927)
86. Karapetis, C.S.; Khambata-Ford, S.; Jonker, D.J.; O'Callaghan, C.J.; Tu, D.; Tebbutt, N.C.; Simes, R.J.; Chalchal, H.; Shapiro, J.D.; Robitaille, S.; Price, T.J.; Shepherd, L.; Au, H.J.; Langer, C.; Moore, M.J.; Zalcberg, J.R. K-ras mutations and benefit from cetuximab in advanced colorectal cancer. N. Engl. J. Med., 2008, 359(17), 1757-1765.
87. Li, W.Q.; Kawakami, K.; Ruszkiewicz, A.; Bennett, G.; Moore, J.; Iacopetta, B. BRAF mutations are associated with distinctive clinical, pathological and molecular features of colorectal cancer independently of microsatellite instability status. Mol. Cancer, 2006, 5, 2.
88. Di Nicolantonio, F.; Martini, M.; Molinari, F.; Sartore-Bianchi, A.; Arena, S.; Saletti, P.; De Dosso, S.; Mazzucchelli, L.; Frattini, M.; Siena, S.; Bardelli, A. Wild-type BRAF is required for response to panitumumab or cetuximab in metastatic colorectal cancer. J. Clin. Oncol., 2008, 26, 5705-5712.
89. Van Cutsem, E.; Lang, I.; Folprecht, G.; Nowacki, M.; Barone, C.; Shchepotin, I.; Maurel, J.; Cunningham, D.; Celik, I.; Kohne, C. In: Cetuximab plus FOLFIRI: Final data from the CRYSTAL study on the association of KRAS and BRAF biomarker status with treatment outcome, Proceedings of the 2010 American Society of Clinical Oncology Annual Meeting, Chicago, Illinois, June 4-8, 2010; Journal of Clinical Oncology: 2010; Abstr 3570.
90. Folkman, J. Angiogenesis in cancer, vascular, rheumatoid and other disease. Nat. Med., 1996, 1, 27-31.
91. Ferrara, N. VEGF and the quest for tumour angiogenesis factors. Nat. Rev. Cancer, 2002, 2, 795-803. (Pubitemid 37328914)
92. Hicklin, D.J.; Ellis, L.M. Role of the vascular endothelial growth factor pathway in tumor growth and angiogenesis. J. Clin. Oncol., 2005, 23, 1011-1027. (Pubitemid 46202320)
93. Shibuya, M.; Claesson-Welsh, L. Signal transduction by VEGF receptors in regulation of angiogenesis and lymphangiogenesis. Exp. Cell Res., 2006, 312, 549-560 (Pubitemid 43290332)
94. Kerbel, R.S. Tumor Angiogenesis. N. Engl. J. Med., 2008, 358, 2039-2049. (Pubitemid 351656458)
95. Choi, H.J.; Hyun, M.S.; Jung, G.J.; Kim, S.S.; Hong, S.H. Tumor angiogenesis as a prognostic predictor in colorectal carcinoma with special reference to mode of metastasis and recurrence. Oncology, 1998, 55, 575-581. (Pubitemid 28479118)
96. Ellis, L.M. Angiogenesis and its role in colorectal tumor and metastasis formation. Semin. Oncol., 2004, 31(6 suppl 17), 3-9. (Pubitemid 40193370)
97. Inai, T.; Mancuso, M.; Hashizume, H.; Baffert, F.; Haskell, A.; Baluk, P.; Hu-Lowe, D.D.; Shalinsky, D.R.; Thurston, G.; Yancopoulos, G.D.; McDonald, D.M. Inhibition of vascular endothelial growth factor (VEGF) signaling in cancer causes loss of endothelial fenestrations, regression of tumor vessels, and appearance of basement membrane ghosts. Am. J. Pathol., 2004, 165, 35-52. (Pubitemid 38821812)
98. Jain, R.K. Normalization of tumor vasculature: an emerging concept in antiangiogenic therapy. Science, 2005, 307, 58-62. (Pubitemid 40093472)
99. Wildiers, H.; Guetens, G.; De Boeck, G.; Verbeken, E.; Landuyt, B.; Landuyt, W.; de Bruijn, E.A.; van Oosterom, A.T. Effect of antivascular endothelial growth factor treatment on the intratumoral uptake of CPT-11. Br. J. Cancer, 2003, 88, 1979-1986. (Pubitemid 36829677)
100. Dallas, N.A.; Fan, F.; Gray, M.J.; Van Buren, G. 2nd.; Lim, S.J.; Xia, L.; Ellis, L.M. Functional significance of vascular endothelial growth factor receptors on gastrointestinal cancer cells. Cancer Metast. Rev., 2007, 26, 433-441. (Pubitemid 350115100)
101. Rovati, B.; Manzoni, M.; Bencardino, K.; Ronzoni, M.; Mariucci, S.; Loupakis, F.; Gattoni, E.; Villa, E.; Falcone, A.; Danova, M. In: The effect of bevacizumab plus chemotherapy on the immunological profile of advanced colorectal cancer patients, Proceedings of the 2008 American Society of Clinical Oncology Annual Meeting, Chicago, Illinois, May 30-June 3, 2008; Journal of Clinical Oncology: 2008; Abstr 14579.
102. European Medicines Agency, 2005.
103. Miles, D. Management of toxicity in patients receiving therapy with bevacizumab. Eur. J. Cancer Suppl., 2008, 6, 29-39.
104. Purdie, D.M.; Berlin, J.D.; Flynn, P.J.; Grothey, A.; Kabbinavar, F.F.; Kozloff, M.F.; Dong, W.; Sugrue, M.M. In: The safety of long-term bevacizumab use: Results from the BRiTE observational cohort study (OCS), Proceedings of the 2008 American Society of Clinical Oncology Annual Meeting, Chicago, Illinois, May 30-June 3, 2008; Journal of Clinical Oncology: 2008; Abstr 4103.
105. Hood, J.D.; Meininger, C.J.; Ziche, M.; Granger, H.J. VEGF upregulates ecNOS message, protein, and NO production in human endothelial cells. Am. J. Physiol., 1998, 274(3 Pt 2), H1054-1058.
106. Hurwitz, H.; Fehrenbacher, L.; Novotny, W.; Cartwright, T.; Hainsworth, J.; Heim, W.; Berlin, J.; Baron, A.; Griffing, S.; Holmgren, E.; Ferrara, N.; Fyfe, G.; Rogers, B.; Ross, R.; Kabbinavar, F. Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N. Engl. J. Med., 2004, 350, 2335-2342. (Pubitemid 38702844)
107. Kabbinavar, F.; Hurwitz, H.I.; Fehrenbacher, L.; Meropol, N.J.; Novotny, W.F.; Lieberman, G.; Griffing, S.; Bergsland, E. Phase II, randomized trial comparing bevacizumab plus fluorouracil (FU)/leucovorin (LV) with FU/LV alone in patients with metastatic colorectal cancer. J. Clin. Oncol., 2003, 21, 60-65.
108. Kabbinavar, F.F.; Schulz, J.; McCleod, M.; Patel, T.; Hamm, J.T.; Hecht, J.R.; Mass, R.; Perrou, B.; Nelson, B.; Novotny, W.F. Addition of bevacizumab to bolus fluorouracil and leucovorin in first-line metastatic colorectal cancer: results of a randomized phase II trial. J. Clin. Oncol., 2005, 23, 3697-3705.
109. Kabbinavar, F.F.; Hambleton, J.; Mass, R.D.; Hurwitz, H.I.; Bergsland, E.; Sarkar, S. Combined analysis of efficacy: The addition of bevacizumab to fluorouracil/leucovorin improves survival for patients with metastatic colorectal cancer. J. Clin. Oncol., 2005, 23, 3706-3712.
110. Sobrero, A.; Ackland, A.; Carrion, R.P.; Chiara, S.; Clarke, S.; Giron, C.G.; Langer, B.; Zurlo, A.; Young, S. on behalf of the AVIRI investigators. In: Efficacy and safety of bevacizumab in combination with irinotecan and infusional 5-FU as first-line treatment for patients with metastatic colorectal cancer, Proceedings of the 2006 American Society of Clinical Oncology Annual Meeting, Atlanta, Georgia, June 2-6, 2006; Journal of Clinical Oncology: 2006; Abstr 3544.
111. Kopetz, S.; Abbruzzese, J.L.; Eng, C.; Adinin, R.B.; Morris, J.; Wolff, R.A.; Lin, E.; Chang, D.Z.; Hoff, P.; Bogaard, K. In: Preliminary results from a phase II study of infusional 5-FU, leucovorin, and irinotecan (FOLFIRI) plus bevacizumab as first-line treatment for metastatic colorectal cancer (mCRC), Proceedings of the 2006 American Society of Clinical Oncology Annual Meeting, Atlanta, Georgia, June 2-6, 2006; Journal of Clinical Oncology: 2006; Abstr 3579.
112. Fuchs, C.S.; Marshall, J.; Mitchell, E.; Wierzbicki, R.; Ganju, V.; Jeffery, M.; Schulz, J.; Richards, D.; Soufi-Mahjoubi, R.; Wang, B.; Barrueco, J. Randomized, controlled trial of irinotecan plus infusional, bolus, or oral fluoropyrimidines in first-line treatment of metastatic colorectal cancer: results from the BICC-C Study. J. Clin. Oncol., 2007, 25, 4779-4786. (Pubitemid 350086481)
113. Hochster, H.S.; Hart, L.L.; Ramanathan, R.K.; Hainsworth, J.D.; Hedrick, E.E.; Childs, B.H. In: Safety and efficacy of oxaliplatin/fluoropyrimidine regimens with or without bevacizumab as first-line treatment of metastatic colorectal cancer (mCRC): Final analysis of the TREE-Study, Proceedings of the 2006 American Society of Clinical Oncology Annual Meeting, Atlanta, Georgia, June 2-6, 2006; Journal of Clinical Oncology: 2006; Abstr 3510.
114. Saltz, L.B.; Clarke, S.; Díaz-Rubio, E.; Scheithauer, W.; Figer, A.; Wong, R.; Koski, S.; Lichinitser, M.; Yang, T.S.; Rivera, F.; Couture, F.; Sirzén, F.; Cassidy, J. Bevacizumab in combination with oxaliplatin-based chemotherapy as first-line therapy in metastatic colorectal cancer: a randomized phase III study. J. Clin. Oncol., 2008, 26, 2013-2019.
115. Kozloff, M.; Hainsworth, J.; Badarinath, S.; Cohn, A.; Flynn, P.J.; Dong, W.; Suzuki, S.; Sarkar, S.; Sugrue, M.M.; Grothey, A. In: Survival of patients (pts) with mCRC treated with bevacizumab in combination with chemotherapy: Results from the BRiTE registry, Proceedings of the 2007 American Society of Clinical Oncology Gastrointestinal Cancers Symposium, Orlando, Florida, January 19-21, 2007; Abstr 375.
116. Van Cutsem, E.; Michael, M.; Berry, S.; Dibartolomeo, M.; Rivera, F.; Kretzschmar, A.; Mazier, M.; Lutiger, B.; Cunningham, D. In: Preliminary safety and efficacy of bevacizumab with first-line FOLFOX, XELOX, FOLFIRI, and capecitabine for mCRC: First BEATrial, Proceedings of the 2007 American Society of Clinical Oncology Gastrointestinal Cancers Symposium, Orlando, Florida, January 19-21, 2007; Abstr 346.
117. Grothey, A.; Sugrue, M.M.; Purdie, D.M.; Dong, W.; Sargent, D.; Hedrick, E.; Kozloff, M. Bevacizumab beyond first progression is associated with prolonged overall survival in metastatic colorectal cancer: results from a large observational cohort study (BRiTE). J. Clin. Oncol., 2008, 26, 5326-5334.
118. Giantonio, B.J.; Catalano, P.J.; Meropol, N.J.; O'Dwyer, P.J.; Mitchell, E.P.; Alberts, S.R.; Schwartz, M.A.; Benson, A.B. 3rd.; Eastern Cooperative Oncology Group Study E3200. Bevacizumab in combination with oxaliplatin, fluorouracil, and leucovorin (FOLFOX4) for previously treated metastatic colorectal cancer: results from the Eastern Cooperative Oncology Group Study E3200. J. Clin. Oncol., 2007, 25, 1539-1544.
119. Gruenberger, B.; Tamandl, D.; Schueller, J.; Scheithauer, W.; Zielinski, C.; Herbst, F.; Gruenberger, T. Bevacizumab, capecitabine, and oxaliplatin as neoadjuvant therapy for patients with potentially curable metastatic colorectal cancer. J. Clin. Oncol., 2008, 26, 1830-1835.
120. Allegra, C.J.; Yothers, G.; O'Connell, M.J.; Sharif, S.; Wolmark, N. In: Initial safety report of NSABP C-08, a randomized phase III study of modified 5-fluorouracil (5-FU)/leucovorin (LCV) and oxaliplatin (OX) (mFOLFOX6) with or without bevacizumab (bev) in the adjuvant treatment of patients with stage II/III colon cancer, Proceedings of the 2008 American Society of Clinical Oncology Annual Meeting, Chicago, Illinois, May 30- June 3, 2008; Journal of Clinical Oncology: 2008; Abstr 4006.
121. Wolmark, N.; Yothers, G.; O'Connell, M.J.; Sharif, S.; Atkins, J.N.; Seay, T.E.; Feherenbacher, L.; O'Reilly, S.; Allegra, C.J. In: A phase III trial comparing mFOLFOX6 to mFOLFOX6 plus bevacizumab in stage II or III carcinoma of the colon: Results of NSABP Protocol C-08, Proceedings of the 2009 American Society of Clinical Oncology Annual Meeting, Orlando, Florida, May 29-June 2, 2009; Journal of Clinical Oncology: 2009; Abstr LBA4.
122. Hecht, J.R.; Trarbach, T.; Jaeger, E.; Hainsworth, J.; Wolff, R.; Lloyd, K.; Bodoky, G.; Borner, M.; Laurent, D.; Jacques, C. In: A randomized, doubleblind, placebocontrolled phase III study in patients with metastatic adenocarcinoma of the colon or rectum receiving first-line chemotherapy with oxaliplatin 5-fluorouracil leucovorin and PTK787/ZK222584 or placebo (CONFIRM-1 ), Proceedings of the 2005 American Society of Clinical Oncology Annual Meeting, Orlando, Florida, May 13-17, 2005; Journal of Clinical Oncology: 2005; Abstr 3.
123. Koehne, C.; Bajetta, E.; Lin, E.; Van Cutsem, E.; Hecht, J.; Douillard, J.; Moore, M.; Germond, C.; Laurent, D.; Jacques, C. In: Results of an interim analysis of a multinational randomized, double-blind, phase III study in patients (pts) with previously treated metastatic colorectal cancer (mCRC) receiving FOLFOX4 and PTK787/ZK 222584 (PTK/ZK) or placebo (CONFIRM 2), Proceedings of the 2006 American Society of Clinical Oncology Annual Meeting, Atlanta, Georgia, June 2-6, 2006; Journal of Clinical Oncology: 2006; Abstr 3508.
124. Cunningham, D.; Wong, R.P.; D'haens, G.; Douillard, J.; Robertson, J.; Saunders, O.; Stone, A.M.; Van Cutsem, E. on behalf of the HORIZON I study group. In: A phase II, doubleblind, randomized multicenter study of cediranib with FOLFOX versus bevacizumab with FOLFOX in patients with previously treated metastatic colorectal cancer (mCRC): final PFS results, Proceedings of the 2008 American Society of Clinical Oncology Annual Meeting, Chicago, Illinois, May 30 - June 3, 2008; Journal of Clinical Oncology: 2008; Abstr 4028.
125. Saltz, L.B.; Rosen, L.S.; Marshall, J.L.; Belt, R.J.; Hurwitz, H.I.; Eckhardt, S.G.; Bergsland, E.K.; Haller, D.G.; Lockhart, A.C.; Rocha Lima, C.M.; Huang, X.; DePrimo, S.E.; Chow-Maneval, E.; Chao, R.C.; Lenz, H.J. Phase II trial of sunitinib in patients with metastatic colorectal cancer after failure of standard therapy. J. Clin. Oncol., 2007, 25, 4793-4799. (Pubitemid 350086483)
126. Starling, N.; Cunningham, D.; Vazquez, F.; Hill, P.; Lechuga, M.J.; Brega, N.; Chao, R.; Carrato, A. In: A phase I study of sunitinib in combination with FOLFIRI chemotherapy in treatment naive, metastatic colorectal cancer, Proceedings of the 2007 American Society of Clinical Oncology Gastrointestinal Cancers Symposium, Orlando, Florida, January 19-21, 2007; Abstr 319.
127. Leong, S.; Eckhardt, S.G.; Chan, E.; Chow, L.Q.; Vermeulen, W.; Camidge, D.R.; Rothenberg, L.M.; Chow Maneval, E.; Chao, R.; Lockhart, A.C. In: A phase I study of sunitinib in combination with modified FOLFOX 6 (mFOLFOX6) chemotherapy, Proceedings of the 2007 American Society of Clinical Oncology Gastrointestinal Cancers Symposium, Orlando, Florida, January 19-21, 2007; Abstr 285.
128. Tang, P.; Cohen, S.J.; Bjarnason, G.A.; Kollmannsberger, C.; Virik, K.; MacKenzie, M.J.; Brown, J.; Wang, L.; Chen, A.P.; Moore, M.J. In: Phase II trial of aflibercept (VEGF Trap) in previously treated patients with metastatic colorectal cancer (MCRC): a PMH phase II consortium trial, Proceedings of the 2008 American Society of Clinical Oncology Annual Meeting, Chicago, Illinois, May 30-June 3, 2008; Journal of Clinical Oncology: 2008; Abstr 4027.
129. Ellis, L.M.; Hicklin, D.J. Pathways mediating resistance to vascular endothelial growth factor - targeted therapy. Clin. Cancer. Res., 2008, 14, 6371-6375.
130. Casanovas, O.; Hicklin, D.J.; Bergers, G.; Hanahan, D. Drug resistance by evasion of antiangiogenic targeting of VEGF signaling in late-stage pancreatic islet tumors. Cancer Cell, 2005, 8, 299-309. (Pubitemid 41443415)
131. Fischer, C.; Jonckx, B.; Mazzone, M.; Zacchigna, S.; Loges, S.; Pattarini, L.; Chorianopoulos, E.; Liesenborghs, L.; Koch, M.; De Mol, M.; Autiero, M.; Wyns, S.; Plaisance, S.; Moons, L.; van Rooijen, N.; Giacca, M.; Stassen, J.M.; Dewerchin, M.; Collen, D.; Carmeliet, P. Anti-PlGF inhibits growth of VEGF(R)-inhibitor-resistant tumors without affecting healthy vessels. Cell, 2007, 131, 463-475. (Pubitemid 350007692)
132. Bergers, G.; Hanahan, D. Modes of resistance to anti-angiogenic therapy. Nat. Rev. Cancer., 2008, 8, 592-603.
133. Ridgway, J.; Zhang, G.; Wu, Y.; Stawicki, S.; Liang, W.C.; Chanthery, Y.; Kowalski, J.; Watts, R.J.; Callahan, C.; Kasman, I.; Singh, M.; Chien, M.; Tan, C.; Hongo, J.A.; de Sauvage, F.; Plowman, G.; Yan, M. Inhibition of Dll4 signalling inhibits tumour growth by deregulating angiogenesis. Nature, 2006, 444, 1083-1087. (Pubitemid 46018529)
134. Grunewald, M.; Avraham, I.; Dor, Y.; Bachar-Lustig, E.; Itin, A.; Jung, S.; Chimenti, S.; Landsman, L.; Abramovitch, R.; Keshet, E. VEGF-induced adult neovascularization: recruitment, retention, and role of accessory cells. Cell, 2006, 124, 175-189. (Pubitemid 43069318)
135. Reinmuth, N.; Liu, W.; Jung, Y.D.; Ahmad, S.A.; Shaheen, R.M.; Fan, F.; Bucana, C.D.; McMahon, G.; Gallick, G.E.; Ellis, L.M. Induction of VEGF in perivascular cells defines a potential paracrine mechanism for endothelial cell survival. FASEB J., 2001, 15, 1239-1241.
136. Kopetz, S.; Hoff, P.M.; Morris, J.S.; Wolff, R.A.; Eng, C.; Glover, K.Y.; Adinin, R.; Overman, M.J.; Valero, V.; Wen, S.; Lieu, C.; Yan, S.; Tran, H.T.; Ellis, L.M.; Abbruzzese, J.L.; Heymach, J.V. Phase II trial of infusional fluorouracil, irinotecan, and bevacizumab for metastatic colorectal cancer: Efficacy and circulating angiogenic biomarkers associated with therapeutic resistance. J. Clin. Oncol., 2010, 28, 453-459.
137. Schneider, B.P.; Wang, M.; Radovich, M.; Sledge, G.W.; Badve, S.; Thor, A.; Flockhart, D.A.; Hancock, B.; Davidson, N.; Gralow, J.; Dickler, M.; Perez, E.A.; Cobleigh, M.; Shenkier, T.; Edgerton, S.; Miller, K.D.; ECOG 2100. Association of vascular endothelial growth factor and vascular endothelial growth factor receptor-2 genetic polymorphisms with outcome in a trial of paclitaxel compared with paclitaxel plus bevacizumab in advanced breast cancer: ECOG 2100. J. Clin. Oncol., 2008, 26, 4672-4678.
138. Dellapasqua, S.; Bertolini, F.; Bagnardi, V.; Campagnoli, E.; Scarano, E.; Torrisi, R.; Shaked, Y.; Mancuso, P.; Goldhirsch, A.; Rocca, A.; Pietri, E.; Colleoni, M. Metronomic cyclophosphamide and capecitabine combined with bevacizumab in advanced breast cancer. J. Clin. Oncol., 2008, 26, 4899-4905.
139. Scartozzi, M.; Galizia, E.; Chiorrini, S.; Giampieri, R.; Berardi, R.; Pierantoni, C.; Cascinu, S. Arterial hypertension correlates with clinical outcome in colorectal cancer patients treated with first-line bevacizumab. Ann. Oncol., 2009, 20, 227-230.
140. Koutras, A.K.; Fountzilas, G.; Makatsoris, T.; Peroukides, S.; Kalofonos, H.P. Bevacizumab in the treatment of breast cancer. Cancer Treat. Rev., 2010, 36, 75-82.
141. Hecht, J.R.; Mitchell, E.; Chidiac, T.; Scroggin, C.; Hagenstad, C.; Spigel, D.; Marshall, J.; Cohn, A.; McCollum, D.; Stella, P.; Deeter, R.; Shahin, S.; Amado, R.G. A randomized phase IIIB trial of chemotherapy, bevacizumab, and panitumumab compared with chemotherapy and bevacizumab alone for metastatic colorectal cancer. J. Clin. Oncol., 2009, 27, 672-680.
142. Tol, J.; Koopman, M.; Cats, A.; Rodenburg, C.J.; Creemers, G.J.; Schrama, J.G.; Erdkamp, F.L.; Vos, A.H.; van Groeningen, C.J.; Sinnige, H.A.; Richel, D.J.; Voest, E.E.; Dijkstra, J.R.; Vink-Börger, M.E.; Antonini, N.F.; Mol, L.; van Krieken, J.H.; Dalesio, O.; Punt, C.J. Chemotherapy, bevacizumab, and cetuximab in metastatic colorectal cancer. N. Engl. J. Med., 2009, 360, 563-572.
143. Arnold, D.; Seufferlein, T. Targeted treatments in colorectal cancer: state of the art and future perspectives. Gut, 2010, 59, 838-858.