A dose-escalation phase I trial of nimotuzumab, an antibody against the epidermal growth factor receptor, in patients with advanced solid malignancies

Investigational New Drugs

Volumn 29, Issue 5, 2011, Pages 996-1003

  You, Benoit ^a   Brade, Anthony ^a   Magalhaes, Joao M ^a,b   Siu, Lillian L ^a   Oza, Amit ^a   Lovell, Sonya ^a   Wang, Lisa ^a   Hedley, David W ^a,b   Nicacio, Leonardo V ^c   Chen, Eric X ^a  

^a PRINCESS MARGARET HOSPITAL   (Canada)

^b UNIVERSITY OF TORONTO   (Canada)

^c YM BioSciences Inc   (Canada)

Author keywords

Antibodies; Clinical trial; Epidermal growth factor receptor; Monoclonal; Nimotuzumab; Phase I

Indexed keywords

EPIDERMAL GROWTH FACTOR RECEPTOR; NIMOTUZUMAB; ANTINEOPLASTIC AGENT; LIGAND; MONOCLONAL ANTIBODY; TUMOR MARKER;

ADULT; ADVANCED CANCER; AGED; ANEMIA; ANTINEOPLASTIC ACTIVITY; ARTICLE; CANCER GROWTH; CANCER PATIENT; CANCER SURVIVAL; CHILL; CLINICAL ARTICLE; CLINICAL ASSESSMENT; COLON CANCER; CREATININE BLOOD LEVEL; DIARRHEA; DRUG DOSE ESCALATION; DRUG EFFICACY; DRUG ERUPTION; DRUG WITHDRAWAL; DRY SKIN; ENDOMETRIUM CANCER; FATIGUE; FEMALE; HUMAN; HYPOALBUMINEMIA; HYPOCALCEMIA; HYPONATREMIA; IMMUNOHISTOCHEMISTRY; LYMPHOCYTOPENIA; MALE; MESOTHELIOMA; MULTIPLE CYCLE TREATMENT; NAUSEA; OVERALL SURVIVAL; PANCREAS CANCER; PARTIAL THROMBOPLASTIN TIME; PHASE 1 CLINICAL TRIAL; PRIORITY JOURNAL; PROTEIN EXPRESSION; RECTUM CANCER; SIDE EFFECT; SKIN BIOPSY; SOLID TUMOR; SURVIVAL RATE; TREATMENT RESPONSE; TUMOR BIOPSY; VOMITING; CANCER STAGING; CLINICAL TRIAL; DISEASE COURSE; DOSE RESPONSE; DRUG ANTAGONISM; ENZYMOLOGY; KAPLAN MEIER METHOD; METABOLISM; MIDDLE AGED; NEOPLASM; PATHOLOGY; TIME; TREATMENT OUTCOME;

AGED; ANTIBODIES, MONOCLONAL; ANTIBODIES, MONOCLONAL, HUMANIZED; ANTINEOPLASTIC AGENTS; DISEASE PROGRESSION; DOSE-RESPONSE RELATIONSHIP, DRUG; FEMALE; HUMANS; KAPLAN-MEIER ESTIMATE; LIGANDS; MALE; MIDDLE AGED; NEOPLASM STAGING; NEOPLASMS; RECEPTOR, EPIDERMAL GROWTH FACTOR; TIME FACTORS; TREATMENT OUTCOME; TUMOR MARKERS, BIOLOGICAL;

EID: 84055166762     PISSN: 01676997     EISSN: 15730646     Source Type: Journal    
DOI: 10.1007/s10637-010-9444-0     Document Type: Article

References (34)

1. Mendelsohn J, Baselga J (2003) Status of epidermal growth factor receptor antagonists in the biology and treatment of cancer. J Clin Oncol 21:2787-2799
2. Rivera F, Vega-Villegas ME, Lopez-Brea MF, Marquez R (2008) Current situation of Panitumumab, Matuzumab, Nimotuzumab and Zalutumumab. Acta Oncol 47:9-19
3. Crombet T, Osorio M, Cruz T, Roca C, del Castillo R, Mon R, Iznaga-Escobar N, Figueredo R, Koropatnick J, Renginfo E, Fernandez E, Alvarez D, Torres O, Ramos M, Leonard I, Perez R, Lage A (2004) Use of the humanized anti-epidermal growth factor receptor monoclonal antibody h-R3 in combination with radiotherapy in the treatment of locally advanced head and neck cancer patients. J Clin Oncol 22:1646-1654
4. Crombet T, Torres L, Neninger E, Catala M, Solano ME, Perera A, Torres O, Iznaga N, Torres F, Perez R, Lage A (2003) Pharmacological evaluation of humanized anti-epidermal growth factor receptor, monoclonal antibody h-R3, in patients with advanced epithelial-derived cancer. J Immunother 26:139-148
5. Talavera A, Friemann R, Gomez-Puerta S, Martinez-Fleites C, Garrido G, Rabasa A, Lopez-Requena A, Pupo A, Johansen RF, Sanchez O, Krengel U, Moreno E (2009) Nimotuzumab, an antitumor antibody that targets the epidermal growth factor receptor, blocks ligand binding while permitting the active receptor conformation. Cancer Res 69:5851-5859
6. Crombet-Ramos T, Rak J, Perez R, Viloria-Petit A (2002) Antiproliferative, antiangiogenic and proapoptotic activity of h-R3: A humanized anti-EGFR antibody. Int J Cancer 101:567-575
7. Nair P, Sierra P, Shivu J, Basavaraj C, Melarkode R (2008) Relevance of biomarkers in a phase IIB head and neck trial using nimotuzumab. ASCO 2008 Molecular Markers Proceedings (Abs. 57)
8. Rojo F, Gracias E, Villena N, Cruz T, Corradino I, Cedeño M, Campas C, Sessa C, Crombet T, Albanell J (2008) Pharmacody-namic study of nimotuzumab, an anti-epidermal growth factor receptor (EGFR) monoclonal antibody (MAb), in patients with unresectable squamous cell carcinoma of the head and neck (SCCHN): A SENDO Foundation study. J Clin Oncol 26(Suppl. 20):2008 ASCO Annual Meeting Proceedings (Abs. 6070)
9. Huang XD, Yi JL, Gao L, Xu GZ, Jin J, Yang WZ, Lu TX, Wu SX, Wu RR, Hu WH, Xie WC, Han F, Gao YH, Gao JM, Pan JJ, Chen CB, Lang JY, Li T, Dong Y, Fu YB, Fan L, Li BS, Li J, Wang XH, Chen BX, Gao XS, Zhang P, Wu XW, Hu BQ (2007) Multi-center phase II clinical trial of humanized anti-epidermal factor receptor monoclonal antibody h-R3 combined with radiotherapy for locoregionally advanced nasopharyngeal carcinoma. Zhonghua Zhong Liu Za Zhi 29:197-201
10. Wu RR, Wu SX, Zhao C, Xie FY, Gao JM, Hu WH, Gao YH, Li FY, Cui TT, Lu TX (2007) Phase II clinical trial of h-R3 combined radiotherapy for locoregionally advanced nasopharyngeal carcinoma. Ai Zheng 26:874-879
11. Bode U, Buchen S, Warmuth-Metz M, Pietsch T, Bach F, Fleischhack G (2007) Final report of a phase II trial of nimotuzumab in the treatment of refractory and relapsed high-grade gliomas in children and adolescents. J Clin Oncol 25(Suppl. 18):2007 ASCO Annual Meeting Proceedings (Abs. 2006)
12. Ramos TC, Figueredo J, Catala M, Gonzalez S, Selva JC, Cruz TM, Toledo C, Silva S, Pestano Y, Ramos M, Leonard I, Torres O, Marinello P, Perez R, Lage A (2006) Treatment of high-grade glioma patients with the humanized anti-epidermal growth factor receptor (EGFR) antibody h-R3: report from a phase I/II trial. Cancer Biol Ther 5:375-379
13. Bebb D, Brade AM, Smith C, Rorke S, Sherman I (2008) Preliminary results of an escalating dose phase I clinical trial of the anti-EGFR monoclonal antibody nimotuzumab in combination with external radiotherapy in patients diagnosed with stage IIb, III or IV non-small cell lung cancer unsuitable for radical therapy. J Clin Oncol 26(Suppl. 20):2008 ASCO Annual Meeting Proceedings (Abs. 3037)
14. Casaco A, Lopez G, Garcia I, Rodriguez JA, Fernandez R, Figueredo J, Torres L, Perera A, Batista J, Leyva R, Pena Y, Amador Z, Gonzalez A, Estupinan B, Coca M, Hernandez A, Puig M, Iglesias M, Ramos M, Rodriquez L, Suarez N (2008) Phase I single-dose study of intracavitary-administered Nimotuzumab labeled with 188 Re in adult recurrent high-grade glioma. Cancer Biol Ther 7:333-339
15. Torres LA, Perera A, Batista JF, Hernandez A, Crombet T, Ramos M, Neninger E, Perez M, Sanchez EL, Romero S, Aguilar V, Coca MA, Iznaga-Escobar N (2005) Phase I/II clinical trial of the humanized anti-EGF-r monoclonal antibody h-R3 labelled with 99mTc in patients with tumour of epithelial origin. Nucl Med Commun 26:1049-1057
16. Vallis KA, Reilly RM, Chen P, Oza A, Hendler A, Cameron R, Hershkop M, Iznaga-Escobar N, Ramos-Suzarte M, Keane P (2002) A phase I study of 99mTc-hR3 (DiaCIM), a humanized immunoconjugate directed towards the epidermal growth factor receptor. Nucl Med Commun 23:1155-1164
17. Shah A, Chen E, Jonker D, Zibdawi I, Mackenzie M, Walde J, Siddqui J, Knight G, Rother M, Bebb G (2009) A phase II clinical trial of nimotuzumab, an EGFR monoclonal antibody, in metastatic colorectal cancer. 2009 Gastrointestinal Cancers Symposium Proceedings (Abs. 358)
18. Strumberg D, Scheulen ME, Hilger RA, Krauss J, Marschner N, Lordick F, Bach F, Reuter D, Edler L, Mross K (2006) Safety, efficacy and pharmacokinetics of nimotuzumab, a humanized monoclonal anti-epidermal growth factor receptor (EGFR) antibody, as monotherapy in patients with locally advanced or metastatic pancreatic cancer (PC). J Clin Oncol 24(Suppl. 18):2006 ASCO Annual Meeting Proceedings (Abs. 12504)
19. Therasse P, Arbuck SG, Eisenhauer EA, Wanders J, Kaplan RS, Rubinstein L, Verweij J, Van Glabbeke M, van Oosterom AT, Christian MC, Gwyther SG (2000) New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst 92:205-216
20. Pham NA, Morrison A, Schwock J, Aviel-Ronen S, Iakovlev V, Tsao MS, Ho J, Hedley DW (2007) Quantitative image analysis of immunohistochemical stains using a CMYK color model. Diagn Pathol 2:8
21. Alekshun T, Garrett C (2005) Targeted therapies in the treatment of colorectal cancers. Cancer Control 12:105-110
22. Capdevila J, Elez E, Macarulla T, Ramos FJ, Ruiz-Echarri M, Tabernero J (2009) Anti-epidermal growth factor receptor monoclonal antibodies in cancer treatment. Cancer Treat Rev 35:354-363
23. Garrido G, Rabasa A, Gracia E, Tikhirov I, Crombet-Ramos T, Viloria-Petit A, Kerbel R, Yang E, Perez R (2009) Binding properties of the anti-EGFR monoclonal antibody, nimotuzumab, limit its interaction with the EGFR in renal and epidermal cells. 2009 AACR Annual Meeting Proceedings (Abs. 2763)
24. Newman M, Gerami P, Guitart J, Lertsburapa T, West D, Rosen S, Cianfrocca M, Lacouture M (2009) Histological differentiation of skin toxicity between cetuximab, erlotinib and panitumumab (single ErbB1) and lapatinib (dual ErbB1/2) epidermal growth factor receptor inhibitors. J Clin Oncol 27(Suppl.):2009 ASCO Annual Meeting Proceedings (Abs. e20617)
25. Tikhomirov I, Hidalgo G, Yang E, Sherman I, Rodriguez R (2009) Bivalent binding properties of epidermal growth factor receptor targeted monoclonal antibodies: facots contributing to differences in observed clinical profiles. 2009 AACR Annual Meeting Proceedings (Abs. A36)
26. Debucquoy A, Haustermans K, Daemen A, Aydin S, Libbrecht L, Gevaert O, De Moor B, Tejpar S, McBride WH, Penninckx F, Scalliet P, Stroh C, Vlassak S, Sempoux C, Machiels JP (2009) Molecular response to cetuximab and efficacy of preoperative cetuximab-based chemoradiation in rectal cancer. J Clin Oncol 27:2751-2757
27. Milas L, Mason K, Hunter N, Petersen S, Yamakawa M, Ang K, Mendelsohn J, Fan Z (2000) In vivo enhancement of tumor radioresponse by C225 antiepidermal growth factor receptor antibody. Clin Cancer Res 6:701-708
28. Maréchal R, Nagy N, Verrellen A, Larsimont D, Hendlisz A, Demols A, Demetter P, Van Laethem J (2008) NK cells infiltrate in primary tumor influences response to cetuximab (CTX) in first-line therapy of metastatic colorectal cancer (mCRC). J Clin Oncol 26(Suppl. 20):2008 ASCO Annual Meeting Proceedings (Abs 22008)
29. Fracasso PM, Burris H 3rd, Arquette MA, Govindan R, Gao F, Wright LP, Goodner SA, Greco FA, Jones SF, Willcut N, Chodkiewicz C, Pathak A, Springett GM, Simon GR, Sullivan DM, Marcelpoil R, Mayfield SD, Mauro D, Garrett CR (2007) A phase 1 escalating single-dose and weekly fixed-dose study of cetuximab: pharmacokinetic and pharmacodynamic rationale for dosing. Clin Cancer Res 13:986-993
30. Tan AR, Moore DF, Hidalgo M, Doroshow JH, Poplin EA, Goodin S, Mauro D, Rubin EH (2006) Pharmacokinetics of cetuximab after administration of escalating single dosing and weekly fixed dosing in patients with solid tumors. Clin Cancer Res 12:6517-6522
31. Mandell JW (2003) Phosphorylation state-specific antibodies: applications in investigative and diagnostic pathology. Am J Pathol 163:1687-1698
32. Paavilainen L, Edvinsson A, Asplund A, Hober S, Kampf C, Ponten F, Wester K (2010) The impact of tissue fixatives on morphology and antibody-based protein profiling in tissues and cells. J Histochem Cytochem 58:237-246
33. Vale C, Tierney J, Meade A, Fisher D, Kaplan R, Adams R, Maughan T, Parmar M (2009) Impact of K-ras status on the effects of EGFR-targeted monoclonal antibody (MAb) therapy in advanced colorectal cancer (ACRC): A systematic review and meta-analysis of randomized controlled trials (RCTs). J Clin Oncol 27(Suppl.):2009 ASCO Annual Meeting Proceedings (Abs 4122)
34. Van Cutsem E, Rougier P, Köhne C, Stroh C, Schlichting M, Bokemeyer C (2009) 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. Eur J Cancer Supplements 7(2):2009 ECCO15-ESMO34 Multidisciplinary Congress Proceedings (Abs P-6077)